Inflammatory bowel disease

Summary

Inflammatory bowel disease (MONDO:0005265) is a disease (an umbrella term covering 40 Mondo subtypes) caused by variants in DUOX2 and SLCO2A1, with 73 cohort genes (1,608 GWAS associations across 69 studies) and 1,245 clinical trials. The dominant Reactome pathway is Interleukin-20 family signaling (10 cohort genes). Top therapeutic interventions include mesalamine, vedolizumab, and infliximab.

At a glance

• Causal genes: DUOX2 (GenCC Strong), SLCO2A1 (GenCC Strong)
• Umbrella term: 40 Mondo subtypes
• Cohort genes: 73
• GWAS associations: 1,608
• ClinVar variants: 135
• Clinical trials: 1,245

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inflammatory bowel disease
Mondo ID	MONDO:0005265
EFO	EFO:0003767
MeSH	D015212
OMIM	266600
DOID	DOID:0050589
NCIT	C3138
SNOMED CT	24526004
UMLS	C0021390
MedGen	43877
Is cancer (heuristic)	no

Also known as: autoimmune bowel disorder · IBD · inflammatory bowel disease

Data availability: 135 ClinVar variants · 1,608 GWAS associations (69 studies) · 10 GenCC gene-disease records.

Disease family

An umbrella term covering 40 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inflammatory bowel disease

Related subtypes (1923): inherited bleeding disorder, platelet-type, infantile liver failure, febrile seizures, familial, hereditary hypophosphatemic rickets, hypothyroidism, congenital, nongoitrous, isolated microphthalmia, nephrolithiasis/osteoporosis, hypophosphatemic, anemia, hypochromic microcytic with iron overload, camptodactyly syndrome, Guadalajara, cerebelloparenchymal disorder, Chiari malformation, developmental dysplasia of the hip, bone marrow failure syndrome, Zimmermann-Laband syndrome, autoimmune disease, multisystem, infantile-onset, multinodular goiter, orofacial cleft, spondylocostal dysostosis, X-linked disease, Y-linked disease, autosomal genetic disease, cornea plana, epithelial-stromal TGFBI dystrophy, congenital diarrhea, Klippel-Feil syndrome, familial polycythemia, myopia, inherited aplastic anemia, FG syndrome, hypotrichosis, hereditary Wilms tumor, familial hemolytic anemia, hereditary fallopian tube carcinoma, ariboflavinosis, bronchiectasis, spermatogenic failure, preeclampsia, cataract, celiac disease, ciliopathy, Fuchs’ endothelial dystrophy, hypospadias, bone Paget disease, visceral leishmaniasis, tooth agenesis, nanophthalmia, hydatidiform mole, fibromuscular dysplasia, familial abdominal aortic aneurysm, Adams-Oliver syndrome, Achard syndrome, Achoo syndrome, acroleukopathy, symmetric, acromegaloid changes, cutis verticis gyrata, and corneal leukoma, acromial dimples, adenosine triphosphatase deficiency, anemia due to, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, amastia, bilateral, with ureteral triplication and dysmorphism, amelia and terminal transverse hemimelia, amenorrhea-galactorrhea syndrome, amyotrophic dystonic paraplegia, anal sphincter dysplasia, anal sphincter myopathy, internal, isolated aniridia, aniridia-absent patella syndrome, aniridia, microcornea, and spontaneously Reabsorbed cataract, anisocoria, ankyloglossia, diffuse idiopathic skeletal hyperostosis, annular erythema, anonychia-ectrodactyly, anonychia-onychodystrophy with brachydactyly type b and ectrodactyly, aortic arch interruption, facial palsy, and retinal coloboma, arcus senilis, arms, malformation of, arteries, anomalies of, arteriovenous malformations of the brain, arteritis, familial granulomatous, with juvenile polyarthritis, arthritis, sacroiliac, asymmetric short stature syndrome, PR interval, variation in, aurocephalosyndactyly, Axenfeld-Rieger anomaly with partially absent eye muscles, distinctive face, hydrocephaly, and skeletal abnormalities, azotemia, familial, gastroesophageal reflux disease, beta-amino acids, renal transport of, bladder diverticulum, blepharochalasis, superior, bone pain, periodic, Brachmann-de Lange-like facial changes with microcephaly, metatarsus adductus, and developmental delay, brachymesomelia-renal syndrome, Brachymetatarsus 4, Brachymorphism-onychodysplasia-dysphalangism syndrome, branchial myoclonus with spastic paraparesis and cerebellar ataxia, familial juvenile hypertrophy of the breast, bundle branch block, familial isolated complete right, butyrylesterase 1, Burkitt lymphoma, calcific aortic disease with immunologic abnormalities, familial, cancer, familial, with in vitro Radioresistance, canine teeth, absence of upper permanent, Car factor deficiency, Carabelli anomaly of maxillary molar teeth, carpal displacement, cervical hypertrichosis with underlying kyphoscoliosis, cervical rib disease, cervical vertebral Bridge, cervical vertebral dysplasia, chemodectoma, intraabdominal, with cutaneous angiolipomas, Chondronectin, choroidal osteoma, bilateral, cirrhosis, familial, congenital pseudoarthrosis of clavicle, aorta coarctation, coloboma, ocular, autosomal dominant, uveal coloboma-cleft lip and palate-intellectual disability, colonic varices without portal hypertension, comedones, familial Dyskeratotic, commissural lip pits, coracoclavicular joint, anomalous, cornea guttata with anterior polar cataracts, corneal degeneration, ribbonlike, with deafness, Schnyder corneal dystrophy, fleck corneal dystrophy, Meesmann corneal dystrophy, epithelial recurrent erosion dystrophy, coumarin resistance, coxa vara, cranioacrofacial syndrome, craniofacial-deafness-hand syndrome, craniorhiny, creatine phosphokinase, elevated serum, cryofibrinogenemia, familial primary, cryptotia, familial, isolated cryptophthalmia, Darwinian tubercle of pinna, autosomal dominant deafness - onychodystrophy syndrome, deafness-ear malformation-facial palsy syndrome, keratoderma hereditarium mutilans, deafness, mid-tone neural, deafness, sensorineural, with peripheral neuropathy and arterial disease, deafness, unilateral, deafness with anhidrotic ectodermal dysplasia, dens evaginatus, dens in dente and palatal invaginations, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, dementia/parkinsonism with non-Alzheimer amyloid plaques, primary failure of tooth eruption, dentin dysplasia type I, dentin dysplasia type II, dentin dysplasia-sclerotic bones syndrome, deoxyribose-5-phosphate aldolase deficiency, dentinogenesis imperfecta type 2, dentinogenesis imperfecta type 3, dermal Ridges, patternless, diarrhea, glucose-stimulated secretory, with common variable immunodeficiency, diastema, dental medial, dilution, pigmentary, discrimination, Two-point, reduction 1N, distal osteosclerosis, distichiasis with congenital anomalies of the heart and peripheral vasculature, DNA, satellite, 3, DNA, low-repetitive sequences of, double nail for fifth toe, duodenal ulcer due to antral G-cell hyperfunction, duodenal ulcer, hyperpepsinogenemic 1, dwarfism, Levi type, dwarfism with stiff joints and ocular abnormalities, dystelephalangy, ear antitragus, tag at base of, ear exostoses, ear folding, ear malformation, preauricular fistulae, congenital, ear pits, posterior helical, thickened earlobes-conductive deafness syndrome, ectodermal dysplasia syndrome with distinctive facial appearance and preaxial polydactyly of feet, ectodermal dysplasia with adrenal cyst, ectopia lentis 1, isolated, autosomal dominant, ectopia pupillae, ectrodactyly and ectodermal dysplasia without cleft lip/palate, ectrodactyly-cleft palate syndrome, edema, familial idiopathic, prepubertal, electroencephalographic peculiarity: 14 and 6 per sec. positive spike phenomenon, electroencephalographic peculiarity: fronto-precentral beta wave groups, emphysema, hereditary pulmonary, eosinophilia, familial, Eosinophilopenia, epidermoid cysts, epidermolysis bullosa with deficiency of galactosylhydroxylysyl glucosyltransferase, epidermolysis bullosa with congenital localized absence of skin and deformity of nails, erythema nodosum, familial, esophageal ring, lower, exchondrosis of pinna, posterior, exostoses-anetodermia-brachydactyly type E syndrome, facial spasm, factor VIII and Factor IX, combined deficiency of, factors VIII, IX and XI, combined deficiency of, factor 9 and Factor XI, combined deficiency of, fibrinolytic defect, fibrodysplasia ossificans progressiva, fibula, recurrent dislocation of head of, Floating-Harbor syndrome, flushing of ears and somnolence, focal epithelial hyperplasia of the oral mucosa, fragile site 10Q23, Friedreich ataxia, so-called, with optic atrophy and sensorineural deafness, intellectual disability, FRA12A type, fucosidase regulator, gamma-A-globulin, defect in assembly of, Gamstorp-Wohlfart syndrome, gastric volvulus, intrathoracic, MALT lymphoma, gastric mucosal hypertrophy, genu valgum, st. Helena familial, giant neutrophil leukocytes, globulin anomaly involving beta (2A)-globulin, glomuvenous malformation, Glucoglycinuria, glucose-6-phosphate dehydrogenase-like, glutamic acid decarboxylase, brain, membrane form, glutathione transferase activity toward trans-stilbene oxide, hyperglycinuria, granddad syndrome, Grant syndrome, granulosis rubra nasi, graying of hair, precocious, guanylate kinase 3, hairy nose tip, hairy palms and soles, hand clasping pattern, cavernous hemangiomas of face-supraumbilical midline raphe syndrome, Kasabach-Merritt syndrome, oculoauriculovertebral spectrum with radial defects, hemolytic poikilocytic anemia due to reduced ankyrin binding sites, hemoglobin–variants for which the chain carrying the mutation 1S unknown or uncertain, hepatic adenomas, familial, hernia, double inguinal, heterochromia iridis, histiocytic dermatoarthritis, humeroradial synostosis, 5-hydroxytryptamine oxygenase regulator, orthostatic hypotensive disorder, Streeten type, hypercalciuria, absorptive, 2, hyperheparinemia, hyperhidrosis palmaris ET plantaris, hyperimmunoglobulin G1(A1) syndrome, hyperlipoproteinemia, type II, and deafness, hyperostosis cranialis interna, hyperpigmentation of eyelid, hyperpigmentation of Fuldauer and Kuijpers, hyperproglucagonemia, hyperreflexia, hypersecretion of adrenal androgens, familial, hypotaurinemic retinal degeneration and cardiomyopathy, essential hypertension, genetic, hyperthermia, cutaneous, with headaches and nausea, hyperthyroxinemia, dystransthyretinemic, hypertrophia musculorum vera, hypoparathyroidism-deafness-renal disease syndrome, hypophosphatemic bone disease, hypoxanthine guanine phosphoribosyltransferase suppressor, ichthyosis-cheek-eyebrow syndrome, IgE responsiveness, atopic, fused mandibular incisors, incisors, lower central, absence of, incisors, rotation of upper central, incisors, shovel-shaped, insensitivity to pain with hyperplastic Myelinopathy, insect Stings, hypersensitivity to, interferon antiviral depressor, iris pigment layer, cleavage of, islet cell adenomatosis, intussusception, IVIC syndrome, internal carotid artery, spontaneous dissection of, keloid formation, keratitis fugax hereditaria, keratosis, familial actinic, angioosteohypertrophic syndrome, knuckle pads, Kyrle disease, labia minora, incomplete adhesion of, lactic acidosis, chronic adult form, laryngeal adductor paralysis, lattice degeneration of retina leading to retinal detachment, periodic fever, immunodeficiency, and thrombocytopenia syndrome, leg ulcers, familial, of juvenile onset, lentiginosis, centrofacial neurodysraphic, leukocyte nuclear appendages, hereditary prevalence of, levator-medial rectus synkinesis, lip, hamartomatous, lipoprotein types–Lt system, lipoprotein, variant of beta, lithium transport, low density lipoprotein, variation in molecular weight of, lumbar stenosis, familial, macrocephaly, benign familial, myelodysplastic syndrome associated with isolated del(5q), malocclusion due to protuberant upper front teeth, Mammastatin, mannose 6-phosphate receptor recognition defect, Lebanese type, marfanoid hypermobility syndrome, masticatory muscles, hypertrophy of, maxillofacial dysostosis, Meckel diverticulum, mediosternal depigmentation line, megalodactyly, melanoma tumor antigen Gp90, mental and growth retardation with amblyopia, mesomelic dwarfism of hypoplastic tibia and radius type, metachondromatosis, metachromasia of fibroblasts, metatarsus varus, type 1, microphthalmia, isolated, with corectopia, microspherophakia with hernia, microspherophakia-metaphyseal dysplasia syndrome, milia, multiple eruptive, tooth ankylosis, MOMO syndrome, antigen defined by monoclonal antibody Aj9, antigen defined by monoclonal antibody T87, Monophalangy of great toe, nondisjunction, mullerian aplasia and hyperandrogenism, multiple exostoses with spastic tetraparesis, muscle cramps, familial, muscular atrophy, malignant neurogenic, muscular hypoplasia, congenital universal, of Krabbe, myelinated optic nerve fibers, myopathy with storage of glycoproteins and Glycosaminoglycans, nasal alar collapse, bilateral, nasal bones, absence of, nasal groove, familial transverse, nasal hyperpigmentation, familial transverse, neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome, neuropathy, congenital, with arthrogryposis multiplex, neuropathy, with paraprotein in serum, cerebrospinal fluid and urine, neutropenia, chronic familial, hereditary neutrophilia, nevus anemicus, nevus flammeus of nape of neck, nipples inverted, familial supernumerary nipples, noduli Cutanei, multiple, with urinary tract abnormalities, nose, anomalous shape of, onychogryposis, pedal, with keratosis plantaris and coarse hair, omphalocele, autosomal, ophthalmomandibulomelic dysplasia, ophthalmoplegia, familial static, ophthalmoplegia, familial total, with iris transillumination, ossified ear cartilages, ossicular malformations, familial, osteosclerosis with ichthyosis and fractures, otofaciocervical syndrome, ovalocytosis, hereditary hemolytic, with defective erythropoiesis, osteochondrodysplasia, rhizomelic, with callosal agenesis, thrombocytopenia, hydrocephalus, and hypertension, palmaris longus muscle, absence of, hereditary chronic pancreatitis, pancytopenia and occlusive vascular disease, papillomatosis, confluent and reticulated, papillomatosis, florid, of nipple, Paramolar tubercle of bolk, Parotidomegaly, hereditary bilateral, Passovoy factor defect, patella aplasia/hypoplasia, patella, familial recurrent dislocation of, Pechet factor deficiency, pectus excavatum, pelvic lipomatosis with crossed renal ectopia, pernicious anemia, peroneal nerve, accessory deep, peroxidase, salivary, phagocytosis, plasma-related defect 1N, pheochromocytoma-islet cell tumor syndrome, phlebectasia of lips, phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome, phosphatase, acid, of tissues, phosphoglucomutase 4, 6-phosphogluconolactonase deficiency, phosphoglycoprotein 1, photomyoclonus, diabetes mellitus, deafness, nephropathy, and cerebral dysfunction, Robin sequence-oligodactyly syndrome, pigmented purpuric eruption, pilonidal sinus, platelet adenylate cyclase activity, platelet aggregation, spontaneous, platelet disorder, undefined, platelet factor 3 deficiency, platelet membrane fluidity, platelet responsiveness to adrenaline, depressed, platelet signal processing defect, familial spontaneous pneumothorax, polyposis, intestinal, scattered and discrete, polyposis, intestinal, with multiple exostoses, polyps, multiple and recurrent inflammatory fibroid, gastrointestinal, popliteal cyst, postaxial tetramelic oligodactyly, posterior column ataxia, Guttmacher syndrome, familial male-limited precocious puberty, premature chromatid separation trait, presenile dementia, Kraepelin type, priapism, familial idiopathic, pronation-supination of the forearm, impairment of, proteolytic capacity of plasma, Protrusio acetabuli, pruritus, hereditary localized, pseudoarthrogryposis, Pseudoatrophoderma colli, pseudomonilethrix, pseudoxanthoma elasticum, forme fruste, pterygium colli, isolated, pubic bone dysplasia, pulmonary atresia with ventricular septal defect, pulmonic stenosis, atrial septal defect, and unique electrocardiographic abnormalities, pulmonic stenosis and deafness, pupillary membrane, persistence of, purpura simplex, radial heads, posterior dislocation of, radio-renal syndrome, radius, aplasia of, with cleft lip/palate, ragweed sensitivity, raindrop hypopigmentation, Raynaud disease, recombinant 8 syndrome, red cell permeability defect, red cell phospholipid defect with hemolysis, retinal venous beading, rhiny, ring dermoid of cornea, Rombo syndrome, Robinow-Sorauf syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, aplasia of lacrimal and salivary glands, salivary substance, Clostridium botulinum type, salivary duct calculi, pleomorphic adenoma, cleft palate-large ears-small head syndrome, sella turcica, bridged, sister chromatid exchange, frequency of, skeletal dysplasia with delayed epiphyseal and carpal bone ossification, Somatomedin, embryonic, spastic paraplegia with associated extrapyramidal signs, spastic paraplegia, optic atrophy, and dementia, sperm protamine P4, spinocerebellar ataxia with rigidity and peripheral neuropathy, spinocerebellar atrophy with pupillary paralysis, splenogonadal fusion-limb defects-micrognathia syndrome, splenomegaly syndrome with splenic Germinal center hypoplasia and reduced circulating T helper cells, split lower lip, split-hand and split-foot with hypodontia, Karsch-Neugebauer syndrome, spondylolisthesis, spondylosis, cervical, polycystic ovary syndrome, sternum, premature obliteration of sutures of, storm syndrome, striae distensae, familial, surface antigen, glycoprotein 75, symphalangism of toes, surface polypeptides, anonymous, symphalangism, C. S. Lewis type, distal symphalangism, symphalangism with multiple anomalies of hands and feet, synovial chondromatosis, familial, with dwarfism, syringomas, multiple, talonavicular coalition, tarsal coalition, tear protein, anodal, T-cell Subgroups, non-HLA-linked, teeth, odd shapes of, teeth present at birth, teeth, supernumerary, temperature-sensitive lethal mutation, spermatic cord torsion, tetralogy of fallot and glaucoma, tetramelic monodactyly, thumb deformity, thyroid hormone plasma membrane transport defect, tibial torsion, bilateral medial, toe, fifth, number of phalanges 1N, toe, misshapen, toe, rotated fifth, toes, relative length of first and second, toes, space between first and second, malposition of teeth with or without hypodontia/oligodontia, torus palatinus and torus mandibularis, tremor of intention, ataxia, and lipofuscinosis, trichomegaly, trichoepitheliomas, multiple desmoplastic, trigger thumb, triphalangeal thumb with double phalanges, triphalangeal thumb, Nonopposable, Tristichiasis, humerus trochlea aplasia, Tuftsin deficiency, suppressor of tumorigenicity 3, tune deafness, Undritz anomaly, Upington disease, ureter, bifid or double, ureterocele, urolithiasis, uric acid, autosomal dominant, urinary bladder, atony of, uterine anomalies, vascular helix of umbilical cord, veins, pattern of, on anterior thorax, venular insufficiency, systemic, vertebral hypoplasia with lumbar kyphosis, congenital vertical talus, vestibulocochlear dysfunction, progressive, volvulus of midgut, Woronets trait, ablepharon macrostomia syndrome, familial glucocorticoid deficiency, aganglionosis, total intestinal, agenesis of cerebral white matter, agnathia-otocephaly complex, Moynahan syndrome, alopecia - intellectual disability syndrome, amino aciduria with mental deficiency, dwarfism, muscular dystrophy, osteoporosis, and acidosis, Amobarbital, deficient N-hydroxylation of, amyloidosis of gingiva and conjunctiva, with intellectual disability, gelatinous drop-like corneal dystrophy, amyloidosis, cutaneous bullous, angiomatosis, diffuse Corticomeningeal, of Divry and van Bogaert, aniridia-renal agenesis-psychomotor retardation syndrome, anodontia, anosmia for isobutyric acid, antithrombin, familial hemorrhagic diathesis due to, Aphalangy-hemivertebrae-urogenital-intestinal dysgenesis syndrome, arteriosclerosis, severe juvenile, arthrogryposis, distal, with intellectual disability and characteristic facies, asthma, nasal polyps, and aspirin intolerance, asthma, short stature, and elevated IgA, ataxia with myoclonic epilepsy and presenile dementia, ataxia, deafness, and cardiomyopathy, ataxia-microcephaly-cataract syndrome, atherosclerosis-deafness-diabetes-epilepsy-nephropathy syndrome, Athrombia, essential, atonic-astatic syndrome of Foerster, atrichia with papular lesions, berry aneurysm, cirrhosis, pulmonary emphysema, and cerebral calcification, beta-aminoisobutyric acid, urinary excretion of, biliary malformation with renal tubular insufficiency, Bowen syndrome of multiple malformations, brachydactyly, type A2, with microcephaly, Elsahy-Waters syndrome, Sabinas brittle hair syndrome, hereditary arterial and articular multiple calcification syndrome, camptodactyly-ichthyosis syndrome, congenital disorder of glycosylation, type i/IIx, carboxypeptidase N deficiency, cardiac septal defects with coarctation of the aorta, cardioauditory syndrome of Sanchez Cascos, cardiomyopathy associated with myopathy and sudden death, carnitine deficiency, myopathic, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, premature centromere division, cephalin lipidosis, cerebellar ataxia and neurosensory deafness, cerebellar ataxia, benign, with thermoanalgesia, cerebral angiopathy, dysphoric, cerebral malformation, seizures, hypertrichosis, and overlapping fingers, cerebrocortical degeneration of infancy, cervical vertebrae, agenesis of, CHAND syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, cholestasis with gallstone, ataxia, and visual disturbance, cholesterol pneumonia, chondroitin-6-sulfaturia, defective cellular immunity, nephrotic syndrome, central areolar choroidal dystrophy, chromosomal instability with tissue-specific radiosensitivity, circumvallate placenta syndrome, citrulline transport defect, Juberg-Hayward syndrome, coloboma, ocular, autosomal recessive, Jalili syndrome, convulsive disorder, familial, with prenatal or early onset, corneal dystrophy-perceptive deafness syndrome, corneal degeneration, band-shaped spheroid, congenital hereditary endothelial dystrophy of cornea, Crane-Heise syndrome, cranial nerves, congenital paresis of, cranial nerves, recurrent paresis of, temtamy syndrome, craniosynostosis with anomalies of the cranial base and digits, craniosynostosis-intellectual disability syndrome of 51N and Gettig, craniosynostosis-intellectual disability-clefting syndrome, cryptorchidism, curved nail of fourth toe, Cushing syndrome due to macronodular adrenal hyperplasia, cutis verticis gyrata and intellectual disability, cyanosis and hepatic disease, cysteine Peptiduria, cystic disease of lung, ventriculomegaly-cystic kidney disease, deafness, congenital, and familial myoclonic epilepsy, DOORS syndrome, high myopia-sensorineural deafness syndrome, conductive deafness-malformed external ear syndrome, deafness-vitiligo-achalasia syndrome, deafness-small bowel diverticulosis-neuropathy syndrome, deafness, neural, congenital moderate, deafness, neural, with atypical atopic dermatitis, dextrocardia with unusual facies and microphthalmia, diaminopentanuria, disseminated sclerosis with narcolepsy, Dohle bodies and leukemia, dwarfism, low-birth-weight type, with unresponsiveness to growth hormone, dwarfism, intellectual disability, and eye abnormality, dwarfism, proportionate, with hip dislocation, dysautonomia-like disorder, dysmyelination with jaundice, dystonia with Ringbinden, ectopia lentis 2, isolated, autosomal recessive, ectopia lentis et pupillae, encephalomalacia, multilocular, Fowler syndrome, endocardial fibroelastosis and coarctation of abdominal aorta, endothelial dystrophy, congenital hereditary, with nail hypoplasia, enterocolitis, congenital enteropathy due to enteropeptidase deficiency, protein-losing enteropathy, epidermolysis bullosa with diaphragmatic hernia, epilepsy, photogenic, with spastic diplegia and intellectual disability, celiac disease-epilepsy-cerebral calcification syndrome, epiphyseal dysplasia of femoral head, myopia, and deafness, epithelial squamous dysplasia, keratinizing desquamative, of urinary tract, immunodeficiency 32B, erythema of acral regions, ethanolaminosis, facial abnormalities, kyphoscoliosis, and intellectual disability, lethal faciocardiomelic dysplasia, faciothoracogenital syndrome, Fanconi-like syndrome, fever, familial lifelong persistent, fibrosclerosis, multifocal, focal epithelial hyperplasia, Fraser-like syndrome, Freesia Flowers, inability to smell, Friedreich ataxia and congenital glaucoma, fructose and galactose intolerance, monosodium glutamate sensitivity, gluteal muscles, absence of, GOMBO syndrome, granulocytopenia with immunoglobulin abnormality, grouped pigmentation of the retina, Halothane hepatitis, hemangiomatosis, cutaneous, with associated features, hepatic veno-occlusive disease-immunodeficiency syndrome, Hirschsprung disease with ulnar polydactyly, polysyndactyly of big toes, and ventricular septal defect, familial lipochrome histiocytosis, classic Hodgkin lymphoma, Hooft disease, Hutterite cerebroosteonephrodysplasia syndrome, hydroxyprolinemia, hymen, imperforate, Leydig cell hypoplasia, type 1, hyperleucine-Isoleucinemia, hyperlysinuria with hyperammonemia, hypermetabolism due to defect in mitochondria, hyperopia, high, hyperparathyroidism, neonatal self-limited primary, with hypercalciuria, hyperphosphatemia, polyuria, and seizures, hypertelorism and tetralogy of fallot, hypertrophic neuropathy and cataract, hyperuricemia, infantile, with abnormal behavior and normal hypoxanthine guanine phosphoribosyltransferase, hypoglycemia, leucine-induced, hypoinsulinemic hypoglycemia and body hemihypertrophy, hypogonadism with low-grade mental deficiency and microcephaly, hypogonadism, male, hypohidrosis with abnormal palmar dermal Ridges, hypokalemic alkalosis, familial, with specific renal tubulopathy, hypophosphatemia, renal, with intracerebral calcifications, hypopituitarism, congenital, with central diabetes insipidus, Bamforth-Lazarus syndrome, ichthyosis congenita with biliary atresia, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, ichthyosis, split hairs, and amino aciduria, immunoglobulin d level in plasma, low, channelopathy-associated congenital insensitivity to pain, autosomal recessive, indolylacroyl glycinuria with intellectual disability, inosine phosphorylase deficiency, immune defect due to, internal carotid arteries, hypoplasia of, immunodeficiency with defective T-cell response to interleukin 1, acetylation, slow, isovaleric acid, inability to smell, Jumping Frenchmen of Maine, oculocerebrofacial syndrome, Kaufman type, keratoconus and congenital hip dysplasia, keratoconus posticus circumscriptus, Kniest-like dysplasia with pursed lips and ectopia lentis, Kifafa seizure disorder, specific granule deficiency, Lambotte syndrome, absence deformity of leg-cataract syndrome, leukemia, acute myelocytic, with polyposis coli and colon cancer, lymphoid system deterioration, progressive, lymphopenic hypergammaglobulinemia, antibody deficiency, autoimmune hemolytic anemia, and glomerulonephritis, lysine malabsorption syndrome, macroepiphyseal dysplasia with osteoporosis, wrinkled skin, and aged appearance, macrosomia adiposa congenita, magnesium, elevated red cell, malocclusion and short stature, mandibulofacial dysostosis with mental deficiency, oculotrichoanal syndrome, megaepiphyseal dwarfism, megalencephaly with dysmyelination, megalocornea, mesoaxial hexadactyly and cardiac malformation, metaphyseal chondrodysplasia, Pena type, metaphyseal dysplasia, anetoderma, and optic atrophy, metaphyseal modeling abnormality, skin lesions, and spastic paraplegia, methionine malabsorption syndrome, microcephaly-micromelia syndrome, Jawad syndrome, microphthalmia with hyperopia, retinal degeneration, macrophakia, and dental anomalies, microtia with meatal atresia and conductive deafness, mucus inspissation of respiratory tract, muscular dystrophy, adult-onset, with leukoencephalopathy, muscular hypertonia, lethal, musk, inability to smell, myeloperoxidase deficiency, myopathy, granulovacuolar lobular, with electrical myotonia, myopathy due to malate-aspartate shuttle defect, myopathy with giant abnormal mitochondria, Keipert syndrome, nephropathy - deafness - hyperparathyroidism syndrome, neuroectodermal melanolysosomal disease, neurologic disease, infantile multisystem, with osseous fragility, neuropathy, hereditary motor and sensory, with excessive myelin folding complex, autosomal recessive, neuropathy, painful, obesity-hypoventilation syndrome, ocular myopathy with curare sensitivity, oculocerebral hypopigmentation syndrome of Preus, oculorenocerebellar syndrome, olivopontocerebellar atrophy II, autosomal recessive, Onychotrichodysplasia and neutropenia, ophthalmoplegia totalis with ptosis and miosis, ophthalmoplegic neuromuscular disorder with abnormal mitochondria, optic atrophy, hearing loss, and peripheral neuropathy, autosomal recessive, Opticocochleodentate degeneration, oral sensibility, disturbance of, Primrose syndrome, osteodysplasty, precocious, of Danks, Mayne, and Kozlowski, congenital osteogenesis imperfecta-microcephaly-cataracts syndrome, osteoma of middle ear, otoonychoperoneal syndrome, palant cleft palate syndrome, pancreatic agenesis, pancreatitis, sclerosing cholangitis, and sicca complex, Partington-Anderson syndrome, pellagra-like syndrome, periodontitis, chronic, adult, peripheral neuropathy, ataxia, focal necrotizing encephalopathy, and spongy degeneration of brain, peroneus tertius muscle, absence of, phenformin 4-hydroxylation, Rabson-Mendenhall syndrome, pituitary dwarfism with large sella turcica, plasma clot retraction factor, deficiency of, platelet prostacyclin receptor defect, pleoconial myopathy with salt craving, polycystic kidney, cataract, and congenital blindness, polymyoclonus, infantile, polysaccharide, storage of unusual, polyhydramnios, chronic idiopathic, Prepapillary vascular loops, progesterone resistance, prolactin deficiency, isolated, prolactin deficiency with obesity and enlarged testes, prune belly syndrome with pulmonic stenosis, intellectual disability, and deafness, 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency, Pseudouridinuria and mental defect, pulmonary alveolar microlithiasis, pulmonary atresia-intact ventricular septum syndrome, pulmonary bullae causing pneumothorax, pulmonary venoocclusive disease, pulmonic stenosis, pulmonic stenosis and congenital nephrosis, pyloric atresia, pyropoikilocytosis, hereditary, radiculoneuropathy, fatal neonatal, Ramon syndrome, red skin pigment anomaly of new guinea, Reese retinal dysplasia, renal and mullerian duct hypoplasia, Perlman syndrome, respiratory underresponsiveness to hypoxia and hypercapnia, retinal degeneration and epilepsy, retinal telangiectasia and hypogammaglobulinemia, retinitis pigmentosa inversa with deafness, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, retinopathy, pigmentary, and intellectual disability, rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction, Rowley-Rosenberg syndrome, second metatarsal-metacarpal syndrome, senile plaque formation, short stature-obesity syndrome, Sjogren-Larsson-like ichthyosis without CNS or eye involvement, sodium-potassium-ATPase activity of red cell, growth delay due to insulin-like growth factor I resistance, ataxia, spastic, childhood-onset, autosomal recessive, with optic atrophy and intellectual disability, spastic diplegia and intellectual disability, spastic paraplegia with myoclonic epilepsy, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, spinal muscular atrophy with intellectual disability, spinal muscular atrophy with microcephaly and mental subnormality, familial isolated congenital asplenia, splenoportal vascular anomalies, spondylocostal dysostosis-anal and genitourinary malformations syndrome, subaortic stenosis, membranous, sucrosuria, hiatus hernia and intellectual disability, syndesmodysplasic dwarfism, tardive dyskinesia, taurodontism, teeth, fused, testes, rudimentary, tetraamelia with ectodermal dysplasia and lacrimal duct abnormalities, tetraamelia-multiple malformations syndrome, thalamic degeneration, symmetric infantile, thumb, distal hyperextensibility of, thymic aplasia with fetal death, thymoma, familial, tiglic acidemia, tibia, absence of, with congenital deafness, tongue, pigmented fungiform papillae of, Tryptophanuria with dwarfism, T-substance anomaly, Tyrosinosis, ulna hypoplasia-intellectual disability syndrome, ulnar agenesis and endocardial fibroelastosis, Valinemia, van Bogaert-Hozay syndrome, vascular hyalinosis, isolated right ventricular hypoplasia, vitiligo, progressive, with intellectual disability and urethral duplication, de Sanctis-Cacchione syndrome, xylosidase deficiency, Young syndrome, corpus callosum agenesis-abnormal genitalia syndrome, intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked, CGF1, arthrogryposis, congenital, lower limb, X-linked, hypotonia, congenital nystagmus, ataxia, and abnormal auditory brainstem responses, Simpson-Golabi-Behmel syndrome type 2, episodic muscle weakness, X-linked, radioulnar synostosis, radial ray abnormalities, and severe malformations in the male, Christianson syndrome, Armfield syndrome, radial ray deficiency, X-linked, alpha-thalassemia-myelodysplastic syndrome, cataract, ataxia, short stature, and intellectual disability, Tn polyagglutination syndrome, fragile X syndrome, deafness, cataract, retinitis pigmentosa, and sperm abnormalities, Lisch epithelial corneal dystrophy, synovial sarcoma, cardiomyopathy, fatal fetal, due to myocardial calcification, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, immunodeficiency 47, Meester-Loeys syndrome, midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, Arts syndrome, tubulin, beta, bullous dystrophy, macular type, Nance-Horan syndrome, central incisors, absence of, Charcot-Marie-Tooth peroneal muscular atrophy, X-linked, with aplasia cutis congenita, Abruzzo-Erickson syndrome, X-linked complicated corpus callosum dysgenesis, cutis verticis gyrata, thyroid aplasia, and intellectual disability, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, focal dermal hypoplasia, glutamyl ribose-5-phosphate storage disease, granulomas, congenital cerebral, hemopoietic proliferation, Hhhh syndrome, ichthyosis and male hypogonadism, immunodeficiency, X-linked, with deficiency of 115,000 Dalton surface glycoprotein, immunoglobulin M, level of, impacted teeth, multiple, imprinting gene related to retinoblastoma, jaundice, familial obstructive, of infancy, Kallmann syndrome with spastic paraplegia, modifier, X-linked, for Neurofunctional defects, myelolymphatic insufficiency, nuclear ribonucleic acid, occipital hair, white lock of, omphalocele, X-linked, ophthalmoplegia, external, and myopia, optic atrophy–spastic paraplegia syndrome, Paine syndrome, Pierre Robin syndrome-faciodigital anomaly syndrome, properdin deficiency, X-linked, absent radius-anogenital anomalies syndrome, radiation sensitivity of natural killer activity, reticuloendotheliosis, X-linked, spastic paraparesis-deafness syndrome, spatial visualization, aptitude for, Taqi polymorphism, taurodontism, microdontia, and dens invaginatus, thrombocytopenia with elevated serum IgA and renal disease, thumbs, congenital Clasped, ulnar hypoplasia-split foot syndrome, unique green phenomenon, VACTERL association, X-linked, with or without hydrocephalus, widow’s peak syndrome, hairy ears, Y-linked, ubiquitin-activating enzyme, Y-linked, hypomagnesemia, hypertension, and hypercholesterolemia, mitochondrial, cardiomyopathy, infantile hypertrophic, chloramphenicol toxicity, nephropathy, chronic tubulointerstitial, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, macrocytosis, familial, pancreatic beta cell agenesis with neonatal diabetes mellitus, chondrodysplasia-pseudohermaphroditism syndrome, familial caudal dysgenesis, gonadal agenesis, succinic acidemia, parotid salivary glands, polycystic dysgenetic disease of, enteropathy, familial, with villous edema and immunoglobulin G2 deficiency, pachydermodactyly, familial, angiokeratoma corporis diffusum with arteriovenous fistulas, pigment dispersion syndrome, setting-Sun phenomenon, familial benign, enuresis, nocturnal, 1, varicella, severe recurrent, dwarfism, familial, with muscle spasms, isoproterenol-mediated vasodilatation, nocturnal enuresis, 2, mitochondrial import-stimulating factor, hereditary hyperferritinemia with congenital cataracts, ectodermal dysplasia with intellectual disability and syndactyly, enamel hypoplasia, cataracts, and aqueductal stenosis, protocadherin 3, cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies, portal vein, cavernous transformation of, midline malformations, multiple, with limb abnormalities and hypopituitarism, ichthyosis-intellectual disability syndrome with large keratohyalin granules in the skin, Ayme-Gripp syndrome, guanylate cyclase 2E, trisomy 18-like syndrome, muscular dystrophy, congenital, with severe central nervous system atrophy and absence of large myelinated fibers, osteoporosis-oculocutaneous hypopigmentation syndrome, myeloid tumor suppressor, epithelial basolateral chloride conductance regulator, rabbit, homolog of, atrophia maculosa varioliformis cutis, familial, spinal dysplasia, Anhalt type, Martinez-Frias syndrome, myelodysplasia, immunodeficiency, facial dysmorphism, short stature, and psychomotor delay, ectrodactyly of lower limbs, congenital heart defect, and micrognathia, short stature, Brussels type, deafness-epiphyseal dysplasia-short stature syndrome, amelia cleft lip palate hydrocephalus iris coloboma, distal monosomy 10p, cervical ribs, Sprengel anomaly, anal atresia, and urethral obstruction, microcephaly, corpus callosum dysgenesis, and cleft lip/palate, anterior chamber cleavage disorder, cerebellar hypoplasia, hypothyroidism, and tracheal stenosis, progressive deafness with stapes fixation, patent ductus venosus, ribbing disease, microcephaly, retinitis pigmentosa, and sutural cataract, facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome, spastic paraplegia and Evans syndrome, iris pigment epithelium anomalies, acute insulin response, sebaceous gland hyperplasia, familial presenile, superior transverse scapular ligament, calcification of, familial, Spondylospinal thoracic dysostosis, acroosteolysis-keloid-like lesions-premature aging syndrome, vacuolar Neuromyopathy, sperm-specific antigen 1, otofacioosseous-gonadal syndrome, broad terminal phalanges, familial, capillary infantile hemangioma, medium chain 3-ketoacyl-Coa thiolase deficiency, ventriculomegaly with defects of the radius and kidney, mitochondrial intermembrane space protein Tim12, yeast, homolog of, sensorineural hearing loss, retinal pigment epithelium lesions, discolored teeth, Weyers ulnar ray/oligodactyly syndrome, creases, infra-auricular cutaneous, with tall stature and advanced bone age, pseudoacromegaly with severe insulin resistance, grange syndrome, jejunal atresia with renal adysplasia, microcephaly, macrotia, and intellectual disability, facial dysmorphism, cleft palate, hearing loss, and camptodactyly, brachydactyly, intraventricular septal defect, and deafness, emphysema, congenital, with deafness, penoscrotal web, and intellectual disability, pancreatic lymphoma, familial, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, skeletal dysplasia and progressive central nervous system degeneration, lethal, intellectual disability, severe, with spasticity and pigmentary tapetoretinal degeneration, tumor suppressor gene on chromosome 11, spastic paraplegia, optic atrophy, microcephaly, and 10Y sex reversal, apraxia of eyelid opening, dislocated elbows, bowed tibias, scoliosis, deafness, cataract, microcephaly, and intellectual disability, muscular dystrophy, congenital, with cerebellar atrophy, GRACILE syndrome, familial gestational hyperthyroidism, long chain fatty acids, defect in transport of, Osebold skeletal dysplasia/osteolysis syndrome, osteosclerotic chondrodysplasia, lethal, with intracellular inclusions, microcephaly, severe, with skeletal anomalies including posterior rib-Gap defects, Tonoki syndrome, expansile bone lesions, Oroacral syndrome, Verloes-Koulischer type, Dyserythropoiesis, congenital, with ultrastructurally normal erythroblast heterochromatin, microcephaly, facial abnormalities, micromelia, and intellectual disability, follicular atrophoderma, perioral pigmented, with milia and epidermoid cysts, parotitis, juvenile recurrent, facial dysmorphism, selective tooth agenesis, and choroid calcification, osteoma of cranial vault, familial, neuroendocrine carcinoma of salivary glands, sensorineural hearing loss, and enamel hypoplasia, atrial septal defect, secundum, with various cardiac and Noncardiac defects, exostosis, Dupuytren subungual, eccrine syringofibroadenomatosis with eyelid abnormalities, blue nevi, familial multiple, blepharophimosis - intellectual disability syndrome, SBBYS type, Acrodysplasia with ossification abnormalities, short stature, and fibular hypoplasia, intervertebral disk degenerative disorder, Caronte, cholesteatoma, congenital, Hirschsprung disease with heart defects, laryngeal anomalies, and preaxial polydactyly, Chudley-McCullough syndrome, camera-Marugo-Cohen syndrome, anemia, congenital hypoplastic, with multiple congenital anomalies/intellectual disability syndrome, myoclonic epilepsy, congenital deafness, macular dystrophy, and psychiatric disorders, ulnar ray dysgenesis with postaxial polydactyly and renal cystic dysplasia, lissencephaly, familial, with cleft palate and cerebellar hypoplasia, polyneuropathy, lethal neonatal, axonal sensorimotor, autosomal recessive, growth and developintellectual disability, ocular ptosis, cardiac defect, and anal atresia, polycystic bone disease, mandibulofacial dysostosis syndrome, Bauru type, hyaluronan metabolism, defect 1N, wormian bone-multiple fractures-dentinogenesis imperfecta-skeletal dysplasia, Wolfram syndrome 2, diabetes mellitus, congenital autoimmune, low density lipoprotein cholesterol, mild elevation of, clavicular hypoplasia, zygomatic arch hypoplasia, and micrognathia, early response to neural induction gene, pseudohyperaldosteronism type 2, Wiedemann-Steiner syndrome, frontoocular syndrome, fibromatosis, gingival, with hypertrichosis and intellectual disability, tetralogy of fallot syndrome, autosomal recessive, anisomastia, ovarian dysgenesis, hypergonadotropic, with short stature and recurrent metabolic acidosis, short stature, intellectual disability, callosal agenesis, Heminasal hypoplasia, microphthalmia, and atypical clefting, arthropathy, erosive, liver fibrocystic disease and polydactyly, crumpled helices and small mouth, acromegaloid features, overgrowth, cleft palate, and hernia, Sener syndrome, baculum, congenital absence of, carnitine acetyltransferase deficiency, laryngeal abductor paralysis with cerebellar ataxia and motor neuropathy, intellectual disability, short stature, facial anomalies, and joint dislocations, Phelan-McDermid syndrome, intellectual disability, microcephaly, growth retardation, joint contractures, and facial dysmorphism, alveolar soft part sarcoma, pathological gambling, Megarbane syndrome, partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome, gastrointestinal stromal tumor, hemifacial myohyperplasia, peripheral arterial occlusive disease 1, parasomnia, sleep bruxism type, Cardioneuromyopathy with hyaline masses and nemaline rods, Cree intellectual disability syndrome, primary intraosseous venous malformation, duodenojejunal atresia with volvulus, absent dorsal mesentery, and absent superior mesenteric artery, symphalangism, distal, with microdontia, dental pulp stones, and narrowed zygomatic arch, COPD, severe early onset, laryngeal atresia, encephalocele, and limb deformities, epilepsy, partial, with pericentral spikes, hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration, horizontal gaze palsy with progressive scoliosis, streptococcus, group A, severity of infection by, thyroid Hurthle cell carcinoma, headache associated with sexual activity, Camptosynpolydactyly, complex, secretory diarrhea, myopathy, and deafness, spastic paraplegia, ataxia, and intellectual disability, breath-holding Spells, prostate cancer aggressiveness quantitative trait locus on chromosome 19, microphthalmia with cyst, bilateral facial clefts, and limb anomalies, cataract, congenital, with mental impairment and dentate gyrus atrophy, craniolenticulosutural dysplasia, nonimmune chronic idiopathic neutropenia of adults, caudal duplication, Thai symphalangism syndrome, bile and pancreatic ducts, complete absence of, ovarian hyperstimulation syndrome, zinc deficiency, transient neonatal, aspirin resistance, mandibulofacial dysostosis with ptosis, autosomal dominant, parathyroid gland carcinoma, growth failure, microcephaly, intellectual disability, cataracts, large joint contractures, osteoporosis, cortical dysplasia, and cerebellar atrophy, scimitar anomaly, multiple cardiac malformations, and craniofacial and central nervous system abnormalities, capillary malformation-arteriovenous malformation syndrome, speech-sound disorder, alopecia universalis congenita, 10Y gonadal dysgenesis, and laryngomalacia, choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome, brachial palsy, familial congenital, oligodontia-cancer predisposition syndrome, midface hypoplasia, obesity, developmental delay, and neonatal hypotonia, ichthyosis prematurity syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, neuropathy, hereditary sensory and autonomic, adult-onset, with anosmia, growth delay due to insulin-like growth factor type 1 deficiency, sudden infant death-dysgenesis of the testes syndrome, leukoencephalopathy, arthritis, colitis, and hypogammaglobulinema, metaphyseal undermodeling, spondylar dysplasia, and overgrowth, lateral semicircular canal malformation, familial, with external and middle ear abnormalities, Meacham syndrome, marfanoid habitus with situs inversus, peripheral cone dystrophy, Emanuel syndrome, intellectual disability with optic atrophy, facial dysmorphism, microcephaly, and short stature, skeletal dysplasia, rhizomelic, with retinitis pigmentosa, familial hyperthyroidism due to mutations in TSH receptor, umbilicus, familial flat, dandy-walker malformation with occipital cephalocele, autosomal dominant, hypotrichosis, progressive patterned scalp, with wiry hair, onycholysis, and cleft lip/palate, syncope, familial vasovagal, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, chromosome 18 pericentric inversion, colloid cysts of third ventricle, intellectual disability, keratoconus, febrile seizures, and sinoatrial block, Goldberg-Shprintzen syndrome, cleft palate, midfacial hypoplasia, triangular facies, and sensorineural hearing loss, nephropathy, progressive, with deafness, iridogoniodysgenesis and skeletal anomalies, omphalocele, diaphragmatic hernia, and radial ray defects, spondylomegaepiphyseal dysplasia with upper limb mesomelia, punctate calcifications, and deafness, Nguyen syndrome, trichilemmal cyst, short stature and Facioauriculothoracic malformations, 7q11.23 microduplication syndrome, hamartoma, Precalcaneal congenital fibrolipomatous, vasculitis, lymphocytic, cutaneous small vessel, ectodermal dysplasia, sensorineural hearing loss, and distinctive facial features, brachyphalangy, polydactyly, and tibial aplasia/hypoplasia, metaphyseal chondrodysplasia with cone-shaped epiphyses, normal hair, and normal hands, trichoscyphodysplasia, arthrogryposis multiplex with deafness, inguinal hernias, and early death, brachydactyly, coloboma, and anterior segment dysgenesis, congenital stromal corneal dystrophy, Devriendt syndrome, MORM syndrome, kyphoscoliosis 1, esophagitis, eosinophilic, 1, alcohol sensitivity, acute, Kleefstra syndrome, rhizomelic dysplasia, scoliosis, and retinitis pigmentosa, right pulmonary artery, anomalous origin of, familial, preauricular tag, isolated, autosomal dominant, 1, testicular microlithiasis, Koolen-de Vries syndrome, preterm premature rupture of the membranes, insulin-resistance syndrome type A, corticosterone methyloxidase type 2 deficiency, holoprosencephaly, recurrent infections, and monocytosis, deafness with labyrinthine aplasia, microtia, and microdontia, iris pattern, epiphyseal dysplasia, Baumann type, Polyosteolysis-hyperostosis syndrome, Sakoda complex, Potocki-Lupski syndrome, hereditary pulmonary alveolar proteinosis, craniofacial dysplasia - osteopenia syndrome, Mungan syndrome, Tented eyebrows, corticosteroid-binding globulin deficiency, familial cavitary optic disk anomaly, renal tubular acidosis, distal, with nephrocalcinosis, short stature, intellectual disability, and distinctive facies, peripapillary atrophy, beta type, dystonia with cerebellar atrophy, Dauwerse-Peters syndrome, tremor, hereditary essential, and idiopathic normal pressure hydrocephalus, mesomelic dysplasia, camera type, Stevenson-Carey syndrome, Hunter-Macdonald syndrome, hypophosphatemic rickets and hyperparathyroidism, deafness, unilateral, with delayed endolymphatic hydrops, histiocytoma, Angiomatoid fibrous, diastasis recti and weakness of the linea alba, Ewing sarcoma, extraskeletal myxoid chondrosarcoma, bilateral microtia-deafness-cleft palate syndrome, Pseudofolliculitis barbae, skeletal defects, genital hypoplasia, and intellectual disability, endocrine-cerebro-osteodysplasia syndrome, cholestasis-pigmentary retinopathy-cleft palate syndrome, faciocardiomelic syndrome, hypotonia, seizures, and precocious puberty, Megarbane-Jalkh syndrome, Giacheti syndrome, lethal polymalformative syndrome, Boissel type, microcephaly, growth retardation, cataract, hearing loss, and unusual appearance, Stargardt macular degeneration, absent or hypoplastic corpus callosum, intellectual disability, and dysmorphic features, Santos syndrome, CLAPO syndrome, hereditary hypotrichosis with recurrent skin vesicles, hydrops fetalis, nonimmune, with gracile bones and dysmorphic features, trichotillomania, Pseudopili annulati, bile acid malabsorption, primary, 1, syndromic multisystem autoimmune disease due to ITCH deficiency, Birbeck granule deficiency, Warsaw breakage syndrome, chromosome 15q24 deletion syndrome, esophagitis, eosinophilic, 2, Reynolds syndrome, early repolarization associated with ventricular fibrillation, chromosome 4Q32.1-q32.2 triplication syndrome, forsythe-wakeling syndrome, lymphedema-posterior choanal atresia syndrome, agenesis of the corpus callosum and congenital lymphedema, brachydactyly, type A1, with short stature, scoliosis, microcephaly, ptosis, hearing loss, and intellectual disability, odontoid hypoplasia, cocoon syndrome, tuberculin skin test reactivity, absence of, intellectual disability, anterior maxillary protrusion, and strabismus, THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome, mammary-digital-nail syndrome, supernumerary der(22)t(8;22) syndrome, porencephaly-microcephaly-bilateral congenital cataract syndrome, chromosome 1p32-p31 deletion syndrome, Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency, multisystemic smooth muscle dysfunction syndrome, inosine triphosphatase deficiency, fucosyltransferase 6 deficiency, Hirschsprung disease, cardiac defects, and autonomic dysfunction, obesity, hyperphagia, and developmental delay, lipodystrophy, partial, acquired, with low complement component c3, with or without glomerulonephritis, acetyl-coa carboxylase deficiency, Okt4 epitope deficiency, cyanosis, transient neonatal, protein Z deficiency, hydroxyacyl glutathione hydrolase deficiency, trypsinogen deficiency, acetyl-CoA acetyltransferase-2 deficiency, N-acetylaspartate deficiency, anhaptoglobinemia, plasma fibronectin deficiency, recurrent infections associated with rare immunoglobulin isotypes deficiency, hyperbiliverdinemia, myostatin-related muscle hypertrophy, hypertelorism-preauricular sinus-punctual pits-deafness syndrome, craniofacial anomalies and anterior segment dysgenesis syndrome, microcephaly-capillary malformation syndrome, arthrogryposis, Perthes disease, and upward gaze palsy, platelet-activating factor acetylhydrolase deficiency, tetrasomy 18p, EDICT syndrome, cognitive impairment with or without cerebellar ataxia, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, glucocorticoid therapy, response to, transient infantile hypertriglyceridemia and hepatosteatosis, Huppke-Brendel syndrome, psychomotor retardation, epilepsy, and craniofacial dysmorphism, encephalomyopathy, mitochondrial, due to voltage-dependent anion channel deficiency, intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency, hypertelorism and other facial dysmorphism, brachydactyly, genital abnormalities, intellectual disability, and recurrent inflammatory episodes, alar cleft, isolated, facial paresis, hereditary congenital, 3, Malan overgrowth syndrome, metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria, immunodeficiency 28, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome, phosphohydroxylysinuria, facial dysmorphism-immunodeficiency-livedo-short stature syndrome, intellectual disability-strabismus syndrome, estrogen resistance syndrome, severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome, testicular anomalies with or without congenital heart disease, multiple fibroadenoma of the breast, complement factor b deficiency, microcephaly-thin corpus callosum-intellectual disability syndrome, L-ferritin deficiency, macrocephaly-developmental delay syndrome, autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity, chromosome 16 inversion, 0.45-Mb, short stature due to GHSR deficiency, Webb-Dattani syndrome, kallikrein, decreased urinary activity of, short stature due to primary acid-labile subunit deficiency, hyperthyroxinemia, familial dysalbuminemic, congenital analbuminemia, immunodeficiency 37, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, chronic atrial and intestinal dysrhythmia, hyperproinsulinemia, Tenorio syndrome, congenital contractures of the limbs and face, hypotonia, and developmental delay, mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, immunodeficiency 39, mandibulofacial dysostosis with alopecia, congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome, BENTA disease, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, PMP22-RAI1 contiguous gene duplication syndrome, DeSanto-Shinawi syndrome due to WAC point mutation, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome, wooly hair, autosomal recessive 3, leukodystrophy and acquired microcephaly with or without dystonia;, inherited oocyte maturation defect, Lamb-Shaffer syndrome, Luscan-Lumish syndrome, exercise intolerance, riboflavin-responsive, split-foot malformation-mesoaxial polydactyly syndrome, heart and brain malformation syndrome, chorea, childhood-onset, with psychomotor retardation, retinitis pigmentosa and erythrocytic microcytosis, macrocephaly, dysmorphic facies, and psychomotor retardation, MIRAGE syndrome, tall stature-intellectual disability-renal anomalies syndrome, Alazami-Yuan syndrome, ZTTK syndrome, Sifrim-Hitz-Weiss syndrome, short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay, Chitayat syndrome, language delay and attention deficit-hyperactivity disorder/cognitive impairment with or without cardiac arrhythmia, Shashi-Pena syndrome, sudden cardiac failure, infantile, sudden cardiac failure, alcohol-induced, cone-rod dystrophy and hearing loss, lung disease, immunodeficiency, and chromosome breakage syndrome;, uncombable hair syndrome 2, uncombable hair syndrome 3, global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness, Yao syndrome, hypotonia, ataxia, and delayed development syndrome, FRAXF syndrome, arthrogryposis multiplex congenita, aniridia - intellectual disability syndrome, radial deficiency-tibial hypoplasia syndrome, familial pancreatic carcinoma, progeroid syndrome, 17q11.2 microduplication syndrome, hereditary sensory and autonomic neuropathy with deafness and global delay, hereditary neoplastic syndrome, orofaciodigital syndrome, lethal recessive chondrodysplasia, Coffin-Siris syndrome, craniosynostosis, keratoconus, congenital pseudoarthrosis of the limbs, hereditary hemophagocytic lymphohistiocytosis, hereditary dementia, advanced sleep phase syndrome, dysmorphism-cleft palate-loose skin syndrome, oculomaxillofacial dysostosis, isolated congenital breast hypoplasia/aplasia, primary pigmented nodular adrenocortical disease, shoulder and thorax deformity-congenital heart disease syndrome, erythromelalgia, Cornelia de Lange syndrome, familial clubfoot with or without associated lower limb anomalies, hereditary gingival fibromatosis, syndromic microphthalmia, progressive non-infectious anterior vertebral fusion, hereditary hypoparathyroidism, hereditary hyperparathyroidism, familial ovarian cancer, hereditary breast carcinoma, heart-hand syndrome, Kabuki syndrome, familial hyperaldosteronism, lymphoproliferative syndrome, split hand-foot malformation, dysraphism-cleft lip/palate-limb reduction defects syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, hereditary anemia, limb transversal defect-cardiac anomaly syndrome, frontonasal dysplasia, familial visceral myopathy, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, Opitz G/BBB syndrome, oromandibular-limb hypogenesis syndrome, heritable pulmonary arterial hypertension, imperforate oropharynx-costo vetebral anomalies syndrome, familial vesicoureteral reflux, Pilotto syndrome, celiac trunk compression syndrome, 3MC syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, renal-hepatic-pancreatic dysplasia, lethal congenital contracture syndrome, triphalangeal thumb-polysyndactyly syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, van Maldergem syndrome, sclerosteosis, diencephalic-mesencephalic junction dysplasia, familial nonmedullary thyroid carcinoma, multiple synostoses syndrome, T-cell immunodeficiency with epidermodysplasia verruciformis, syngnathia multiple anomalies, syngnathia-cleft palate syndrome, humero-radio-ulnar synostosis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, thrombocytopenia-Robin sequence syndrome, tibial aplasia-ectrodactyly syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, hereditary glaucoma, familial cervical artery dissection, bipartite talus, skeletal dysplasia, acrofacial dysostosis, chronic granulomatous disease, Hirschsprung disease, growth retardation-mild developmental delay-chronic hepatitis syndrome, osteonecrosis of genetic origin, global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome, hereditary gastric cancer, severe congenital neutropenia, hypogonadotropic hypogonadism, GCGR-related hyperglucagonemia, autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome, visceral heterotaxy, hereditary neuroendocrine tumor of small intestine, hereditary otorhinolaryngologic disease, congenital bilateral absence of vas deferens, bile duct cyst, Caroli syndrome, isolated neonatal sclerosing cholangitis, arterial calcification of infancy, branchiootic syndrome, Mazabraud syndrome, familial melanoma, inherited hemoglobinopathy, inborn errors of metabolism, familial thrombocytosis, androgen insensitivity syndrome, central precocious puberty, familial long QT syndrome, inherited obesity, Axenfeld-Rieger syndrome, inherited isolated nail anomaly, lymphatic malformation, ischio-vertebral syndrome, fetal and neonatal alloimmune thrombocytopenia, anterior segment dysgenesis, amelogenesis imperfecta, van der Woude syndrome, familial thoracic aortic aneurysm and aortic dissection, inherited primary ovarian failure, distal arthrogryposis, Ehlers-Danlos syndrome, inherited sideroblastic anemia, posterior polymorphous corneal dystrophy, familial parathyroid adenoma, Simpson-Golabi-Behmel syndrome type 1, sex-linked disease, microcephaly, growth restriction and increased sister chromatid exchange, microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, autosomal dominant wooly hair, congenital short bowel syndrome, autosomal recessive, uncombable hair syndrome 1, Menke-Hennekam syndrome, dwarfism with tall vertebrae, pulmonary alveolar proteinosis with hypogammaglobulinemia, contractures, pterygia, and variable skeletal fusions syndrome, syndactyly, polydactyly, brachydactyly, RASopathy, immunodeficiency disease, laminopathy, inherited blood coagulation disorder, central centrifugal cicatricial alopecia, double fingernail of fifth finger, FRAXD syndrome, familial colorectal cancer, familial partial paralysis, Dursun syndrome, hereditary disorder of connective tissue, Marinesco-Sjogren-like syndrome, WHIM syndrome, visceral neuropathy, familial, neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset, portal hypertension, noncirrhotic, multiple congenital anomalies-neurodevelopmental syndrome, X-linked, azoospermia, obstructive, with nephrolithiasis, megacystis-microcolon-intestinal hypoperistalsis syndrome, Mullegama-Klein-Martinez syndrome, Shukla-Vernon syndrome, Basilicata-Akhtar syndrome, serpinopathy, peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, intellectual developmental disorder with hypertelorism and distinctive facies, Diets-Jongmans syndrome, autoinflammation with episodic fever and lymphadenopathy, retinal dystrophy with leukodystrophy, skeletal dysplasia, mild, with joint laxity and advanced bone age, Nizon-Isidor syndrome, seizures, early-onset, with neurodegeneration and brain calcifications, leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome, proteinuria, chronic benign, Liberfarb syndrome, microcephaly, developmental delay, and brittle hair syndrome, 46,xx sex reversal 5, intellectual developmental disorder with autistic features and language delay, with or without seizures, neurodevelopmental, jaw, eye, and digital syndrome, agenesis of corpus callosum, cardiac, ocular, and genital syndrome, retinitis pigmentosa 89, spondylometaphyseal dysplasia with corneal dystrophy, Teebi hypertelorism syndrome, leukoencephalopathy, hereditary diffuse, with spheroids, gastrointestinal defect and immunodeficiency syndrome, developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, intellectual developmental disorder with speech delay and axonal peripheral neuropathy, vertebral hypersegmentation and orofacial anomalies, cardiofacioneurodevelopmental syndrome, Kaya-Barakat-Masson syndrome, leukoencephalopathy, progressive, infantile-onset, with or without deafness, Lessel-Kreienkamp syndrome, intellectual developmental disorder with paroxysmal dyskinesia or seizures, Li-Campeau syndrome, neurofacioskeletal syndrome with or without renal agenesis, deafness, congenital, and adult-onset progressive leukoencephalopathy, oculomotor-abducens synkinesis, blistering, acantholytic, of oral and laryngeal mucosa, vertebral, cardiac, tracheoesophageal, renal, and limb defects, developmental delay with dysmorphic facies and dental anomalies, Kohlschutter-Tonz syndrome-like, bile acid conjugation defect 1, short stature, oligodontia, dysmorphic facies, and motor delay, global developmental delay with speech and behavioral abnormalities, vitreoretinopathy with phalangeal epiphyseal dysplasia, Baralle-Macken syndrome, dyskinesia with orofacial involvement, inherited interstitial lung disease, Bryant-Li-Bhoj neurodevelopmental syndrome, restrictive dermopathy, Stuve-Wiedemann syndrome, cardiac valvular defect, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardioacrofacial dysplasia, Tessadori-Van-Haaften neurodevelopmental syndrome, Carey-Fineman-Ziter syndrome, thyroid hormone metabolism, abnormal, short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies, developmental delay with short stature, dysmorphic facial features, and sparse hair, Braddock-Carey syndrome, ophthalmoplegia, external, with rib and vertebral anomalies, intellectual developmental disorder with macrocephaly, seizures, and speech delay, cardiac, facial, and digital anomalies with developmental delay, osteochondrodysplasia, brachydactyly, and overlapping malformed digits, warburg-cinotti syndrome, Snijders Blok-Campeau syndrome, inflammatory bowel disease, immunodeficiency, and encephalopathy, vertebral anomalies and variable endocrine and T-cell dysfunction, arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development, trichohepatoneurodevelopmental syndrome, mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, fibrosis, neurodegeneration, and cerebral angiomatosis, cardiac-urogenital syndrome, visual impairment and progressive phthisis bulbi, microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum, macrocephaly, acquired, with impaired intellectual development, mucocutaneous ulceration, chronic, intellectual developmental disorder with cardiac defects and dysmorphic facies, global developmental delay with or without impaired intellectual development, infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, microcephaly, growth deficiency, seizures, and brain malformations, short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, turnpenny-fry syndrome, facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome, leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, global developmental delay, progressive ataxia, and elevated glutamine, metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression, gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, intellectual developmental disorder with short stature and variable skeletal anomalies, developmental delay with or without dysmorphic facies and autism, Khan-Khan-Katsanis syndrome, cerebellar, ocular, craniofacial, and genital syndrome, hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities, congenital hypotonia, epilepsy, developmental delay, and digital anomalies, cerebellar atrophy with seizures and variable developmental delay, O’Donnell-Luria-Rodan syndrome, ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facial features, hypopigmentation, organomegaly, and delayed myelination and development, glycosylphosphatidylinositol biosynthesis defect 21, spastic tetraplegia and axial hypotonia, progressive, snijders blok-fisher syndrome, intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies, lower urinary tract obstruction, congenital, Usher syndrome, type 1M, Siddiqi syndrome, oculopharyngeal myopathy with leukoencephalopathy 1, neurooculocardiogenitourinary syndrome, intellectual developmental disorder with impaired language and dysmorphic facies, hydrocephalus, congenital communicating, 1, intellectual developmental disorder with speech delay, autism, and dysmorphic facies, lessel-kubisch syndrome, intellectual developmental disorder with short stature and behavioral abnormalities, short stature and microcephaly with genital anomalies, megabladder, congenital, Heyn-Sproul-Jackson syndrome, intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, Liang-Wang syndrome, neuromuscular disease and ocular or auditory anomalies with or without seizures, structural brain anomalies with impaired intellectual development and craniosynostosis, pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, intellectual developmental disorder with hypotonia and behavioral abnormalities, Catifa syndrome, CEBALID syndrome, congenital heart defects, multiple types, 7, Imagawa-Matsumoto syndrome, juvenile arthritis due to defect in LACC1, Beck-Fahrner syndrome, respiratory papillomatosis, juvenile recurrent, congenital, sandestig-stefanova syndrome, triokinase and FMN cyclase deficiency syndrome, T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, intellectual developmental disorder with poor growth and with or without seizures or ataxia, pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, chromosome 1p36.33 duplication syndrome, atad3 gene cluster, autosomal dominant, genitourinary and/or brain malformation syndrome, rhizomelic limb shortening with dysmorphic features, Suleiman-El-Hattab syndrome, cone-rod synaptic disorder syndrome, congenital nonprogressive, Tolchin-Le Caignec syndrome, Li-Ghorbani-Weisz-Hubshman syndrome, autoinflammation, immune dysregulation, and eosinophilia, intellectual developmental disorder with seizures and language delay, mitochondrial complex 1 deficiency, nuclear type 35, deeah syndrome, combined oxidative phosphorylation deficiency 49, combined oxidative phosphorylation deficiency 50, Vissers-Bodmer syndrome, spinal muscular atrophy, infantile, James type, vitamin D-dependent rickets, type 3, cleft palate, proliferative retinopathy, and developmental delay, microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, early-onset familial hypoaldosteronism, chronic mast cell leukemia, DONSON-related microcephaly-short stature-limb abnormalities spectrum, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome, cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome, KLHL7-related Bohring-Opitz-like syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, inherited auditory system disease, Y chromosome infertility due to DAZ1 deletion, familial osteosclerosis, foveal hypoplasia, congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, congenital heart defects and ectodermal dysplasia, brachycephaly, trichomegaly, and developmental delay, thrombocytopenia, anemia, and myelofibrosis, structural heart defects and renal anomalies syndrome, Rahman syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, familial monosomy 7 syndrome, menstrual cycle-dependent periodic fever, Gabriele de Vries syndrome, Lopes-Maciel-Rodan syndrome, Skraban-Deardorff syndrome, amyotonia congenita, cerebral sclerosis, diffuse, scholz type, autoinflammation with arthritis and dyskeratosis, retinal dystrophy with or without macular staphyloma, Cohen-Gibson syndrome, maleylacetoacetate isomerase deficiency, congenital heart defects and skeletal malformations syndrome, microcephaly, short stature, and limb abnormalities, congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, cerebellar atrophy, developmental delay, and seizures, platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, facial palsy, congenital, with ptosis and velopharyngeal dysfunction, immunodeficiency, developmental delay, and hypohomocysteinemia, Sweeney-Cox syndrome, combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia, Alkuraya-Kucinskas syndrome, Diamond-Blackfan anemia-like, hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, chromosome 1p35 deletion syndrome, hyperthyroxinemia, euthyroid, caused by generalized 5-prime-deiodinase deficiency, Jaberi-Elahi syndrome, deafness, congenital heart defects, and posterior embryotoxon, humerofemoral hypoplasia with radiotibial ray deficiency, intellectual developmental disorder with or without epilepsy or cerebellar ataxia, CDKL5 disorder, GATA1-Related X-Linked Cytopenia, focal segmental glomerulosclerosis and neurodevelopmental syndrome, hereditary skin disorder, AP-4 deficiency syndrome, inherited kidney disorder, Mendelian encephalopathy, X inactivation, familial skewed, growth hormone insensitivity syndrome with immune dysregulation, DICER1-related tumor predisposition, A20 haploinsufficiency, LTBP2-related ocular dysgenesis, inherited cutis laxa, inherited hypertrophic pyloric stenosis, inherited thrombocytopenia, multiple congenital anomalies-hypotonia-seizures syndrome, 46,XX sex reversal 1, microcephaly, epilepsy, and diabetes syndrome, SEC61A1 deficiency, achalasia, familial esophageal, MECOM-associated syndrome, TPM4-related platelet disorder, TRAF3 haploinsufficiency, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, hereditary neurological disease, cardiogenetic disease, hereditary narcolepsy, RNU4ATAC spectrum disorder, CTNNB1-related neurodevelopmental disorder and/or vitreoretinopathy, MTOR-related overgrowth spectrum, TOR1AIP1-related nuclear envelopathy, BMP4-related ocular growth disorder, CSF1R-related disorder, acinar dysplasia caused by mutation in FGF10, acinar dysplasia caused by mutation in FGFR2, acinar dysplasia caused by mutation in TBX4, EPHB4-associated vascular malformation spectrum, BAFopathy, hereditary skeletal muscle disorder, hereditary gallbladder disorder, prostate cancer, hereditary, POLR3A-related disorder, POLR3B-related disorder, POLR1C-related disorder, WFS1-related disorder, CACNA1C-related disorder, SMAD6-related disease, central hypoventilation syndrome, congenital, autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency, alopecia universalis, microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 2, myopathy, congenital, with excess of muscle spindles, pregnancy loss, recurrent, 4, urogenital adysplasia, yakut short stature syndrome, microcephaly, short stature, and impaired glucose metabolism, NR2F2 related multiple congenital anomalies/dysmorphic syndrome, ACD-related telomere biology disorder, AKT3-related overgrowth spectrum, rhabdomyosarcoma, embryonal, 2, blepharophimosis-impaired intellectual development syndrome, Radio-Tartaglia syndrome, Buratti-Harel syndrome, growth restriction, hypoplastic kidneys, alopecia, and distinctive facies, fibromuscular dysplasia, multifocal, dysostosis multiplex, Ain-Naz type, ataxia, intention tremor, and hypotonia syndrome, childhood-onset, deafness, cataract, impaired intellectual development, and polyneuropathy, onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, Faundes-Banka syndrome, osteootohepatoenteric syndrome, hypokalemic tubulopathy and deafness, White-Kernohan syndrome, retinal dystrophy and microvillus inclusion disease, Luo-Schoch-Yamamoto syndrome, Usmani-Riazuddin syndrome, autosomal dominant, VISS syndrome, developmental delay, impaired speech, and behavioral abnormalities, bile acid malabsorption, primary, 2, DEGCAGS syndrome, Short stature, Dauber-Argente type, ventriculomegaly and arthrogryposis, Chopra-Amiel-Gordon syndrome, muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome, neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, biliary, renal, neurologic, and skeletal syndrome, Boudin-Mortier syndrome, Usmani-Riazuddin syndrome, autosomal recessive, intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies, developmental delay with or without intellectual impairment or behavioral abnormalities, cerebellar ataxia, brain abnormalities, and cardiac conduction defects, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, delayed puberty, self-limited, Hengel-Maroofian-Schols syndrome, Zaki syndrome, dystonia, early-onset, and/or spastic paraplegia, developmental delay with variable neurologic and brain abnormalities, Rauch-Steindl syndrome, intellectual disability and myopathy syndrome, cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, Kury-Isidor syndrome, macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin, intellectual developmental disorder with or without peripheral neuropathy, neurocardiofaciodigital syndrome, corneal dystrophy, punctiform and polychromatic pre-descemet, osteoporosis, childhood- or juvenile-onset, with developmental delay, hepatorenocardiac degenerative fibrosis, ACCES syndrome, developmental delay, impaired speech, and behavioral abnormalities, with or without seizures, liver disease, severe congenital, primordial dwarfism-immunodeficiency-lipodystrophy syndrome, intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, keratoderma-ichthyosis-deafness syndrome, autosomal recessive, developmental delay, hypotonia, and impaired language, intellectual developmental disorder with autism and dysmorphic facies, bone marrow failure and diabetes mellitus syndrome, developmental delay, behavioral abnormalities, and neuropsychiatric disorders, hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, intellectual developmental disorder with ocular anomalies and distinctive facial features, developmental delay with variable intellectual disability and dysmorphic facies, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 1, developmental delay, language impairment, and ocular abnormalities, Rabin-Pappas syndrome, muscular dystrophy, congenital, with or without seizures, obesity and hypopigmentation, joint contractures, osteochondromas, and B-cell lymphoma, respiratory infections, recurrent, and failure to thrive with or without diarrhea, developmental delay with hypotonia, myopathy, and brain abnormalities, Atelis syndrome, hereditary neuro-ophthalmological disease, autoinflammation with pulmonary and cutaneous vasculitis, neurooculorenal syndrome, combined low LDL and fibrinogen, hypersulfaturia, woolly hair-skin fragility syndrome, hematuria, benign familial, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, disabling pansclerotic morphea of childhood, Houge-Janssens syndrome, hearing loss, noise-induced, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, 12, cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, congenital smooth muscle hamartoma, with or without hemihypertrophy, amegakaryocytic thrombocytopenia, congenital, 2, epilepsy, early-onset, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, immune dysregulation, autoimmunity, and autoinflammation, arrhythmogenic cardiomyopathy with variable ectodermal abnormalities, developmental delay, dysmorphic facies, and brain anomalies, developmental delay with or without epilepsy, craniometadiaphyseal osteosclerosis with hip dysplasia, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, isolated hyperferritinemia, megalencephaly-polydactyly syndrome, autoinflammation with episodic fever and immune dysregulation, autoinflammation with arthritis and vasculitis, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, short stature with nonspecific skeletal abnormalities, bronchiectasis and nasal polyposis, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, spastic paraplegia, mitochondrial, Pan-Chung-Bellen syndrome, autoinflammation, panniculitis, and dermatosis syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, ocular pterygium-digital keloid dysplasia syndrome, Tayoun-Maawali syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Guillouet-Gordon syndrome, immunodysregulation with variable immunodeficiency and autoimmunity, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency, ADNP-related blepharophimosis-intellectual disability syndrome, oculovertebral syndrome, Ververi-Brady syndrome, immune dysregulation, neurodevelopmental defects, and colitis, dyschromatosis, ichthyosis, deafness, and atopic disease, developmental delay with variable cardiac and renal congenital anomalies and dysmorphic facies, developmental delay with sleep apnea, Pitt-Hopkins or Pitt-Hopkins-like syndrome, intellectual developmental disorder, autosomal recessive 84, intellectual developmental disorder, autosomal dominant 77, periodontitis, aggressive, dental radicular dysplasia, intellectual developmental disorder with seizures and dysmorphic facies, STAD syndrome, craniosynostosis-scoliosis syndrome, COL4A1/A2-related disorder, TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations, PI4KA-related disorder, NDUFB11-related disorders, EN1-related dorsoventral syndrome, DHDDS-CDG, PLEC-related muscular dystrophy-epidermolysis bullosa simplex spectrum disorder, FDXR-related optic atrophy mitochondrial dysfunction syndrome, PIK3R1-related immunodeficiency and SHORT syndrome, ACAN-related short stature spectrum, ELANE-related neutropenia, NR5A1-related sex development disorder, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, SYCE1-related gametogenic failure, RNU12-related minor spliceopathy disorder, MCM9-related gametogenic failure, CFTR-related disorder

Subtypes (40): Crohn disease, colitis, proctitis, ulcerative proctosigmoiditis, inflammatory bowel disease 11, cutaneous photosensitivity-lethal colitis syndrome, inflammatory bowel disease 1, inflammatory bowel disease 2, inflammatory bowel disease 3, inflammatory bowel disease 7, inflammatory bowel disease 5, inflammatory bowel disease 8, inflammatory bowel disease 6, inflammatory bowel disease 4, inflammatory bowel disease 9, inflammatory bowel disease 10, inflammatory bowel disease 12, inflammatory bowel disease 13, inflammatory bowel disease 14, inflammatory bowel disease 15, inflammatory bowel disease 16, inflammatory bowel disease 17, inflammatory bowel disease 18, inflammatory bowel disease 19, inflammatory bowel disease 20, inflammatory bowel disease 21, inflammatory bowel disease 22, inflammatory bowel disease 23, inflammatory bowel disease 24, inflammatory bowel disease 26, inflammatory bowel disease 27, undetermined colitis, cap polyposis, IL10-related early-onset inflammatory bowel disease, neonatal inflammatory skin and bowel disease, inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive, inflammatory bowel disease 30, TRIM22-related inflammatory bowel disease, ALPI-related inflammatory bowel disease, inflammatory bowel disease 29

Genetics & variants

GWAS landscape

1,608 GWAS associations across 69 studies. Top hits map to 25 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs7547569	2e-170	IL23R - RNU4ATAC4P	?
rs11209026	8e-161	IL23R	G	2.01
rs11581607	4e-123	IL23R	?	0.6
rs10817678	6e-109	TNFSF15 - DELEC1	?	1.53
rs748670681	9e-93	TNRC18	?	0.82
rs56211063	3e-89	TNFSF15 - DELEC1	?	0.33
rs9275224	3e-87	HLA-DQB1 - MTCO3P1	?
rs11742570	2e-82	RNU1-150P - TTC33	C	1.2
rs4410767	2e-77	HLA-DRB9 - HLA-DRB5	?
rs4409764	3e-72	LINC01475	?	0.16
rs9268557	6e-71	TSBP1-AS1 - HLA-DRA	?
rs755374	5e-67	IL12B-AS1	?	0.17
rs6880778	5e-65	RNU1-150P - TTC33	?
rs10748781	2e-63	LINC01475	?
rs9271511	4e-60	HLA-DRB1 - HLA-DQA1	?	0.16
rs113653754	3e-58	HLA-DQA1 - HLA-DQB1	C	1.21
rs41268924	4e-58	EGFL8, PPT2-EGFL8	?
rs10781499	4e-56	CARD9	A	1.19
rs1131095	2e-55	APEH	?	0.16
rs3024495	5e-55	IL10	?	0.21
rs17212937	6e-55	MTCO3P1 - HLA-DQB3	?
rs34236350	8e-54	GPR35	?	0.17
rs4077515	1e-53	CARD9	?
rs10761659	5e-53	LINC02929 - ALDH7A1P4	G	1.17
rs2188962	1e-52	CARINH	T	1.16
rs9836291	1e-52	BSN	?
rs11236797	9e-52	EMSY - LINC02757	?
rs3024493	2e-50	IL10	?
rs56167332	7e-50	IL12B-AS1	A	1.17
rs2836883	3e-48	LINC02940 - RPL23AP12	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90432147	Jiang Y	2023	116,382	213,325	A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.
GCST90301319	Khrom M	2023	34,579	39,125	Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.
GCST90301320	Khrom M	2023	34,579	39,125	Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.
GCST90428829	Yu X	2024	25,042	51,581	Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis.
GCST004131	de Lange KM	2017	25,042	34,915	Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.
GCST005837	Huang H	2017	20,155	34,257	Fine-mapping inflammatory bowel disease loci to single-variant resolution.
GCST90137951	Yadav P	2017	19,735	4,887	Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.
GCST90137954	Yadav P	2017	19,735	4,887	Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.
GCST90137957	Yadav P	2017	19,735	4,887	Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.
GCST90301318	Khrom M	2023	18,158	22,345	Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	1
Tier 3: regulatory	4
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	22
intergenic_variant	14
missense_variant	3
regulatory_region_variant	3
non_coding_transcript_exon_variant	3
synonymous_variant	2
stop_gained	1
TF_binding_site_variant	1
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs7547569	1	67265685	T>C	0.05	intergenic_variant	IL23R - RNU4ATAC4P	2e-170	Tier 4: intronic/intergenic
rs11209026	1	67240275	G>A,T	0.067	missense_variant	IL23R	8e-161	Tier 1: coding
rs11581607	1	67242007	G>A	0.05	intron_variant	IL23R	4e-123	Tier 4: intronic/intergenic
rs10817678	9	114817177	G>A	0.05	intron_variant	TNFSF15 - DELEC1	6e-109	Tier 4: intronic/intergenic
rs748670681	7	5397122	C>T		intron_variant	TNRC18	9e-93	Tier 4: intronic/intergenic
rs56211063	9	114823617	G>C	0.05	intergenic_variant	TNFSF15 - DELEC1	3e-89	Tier 4: intronic/intergenic
rs9275224	6	32692101	A>C,G	0.05	regulatory_region_variant	HLA-DQB1 - MTCO3P1	3e-87	Tier 3: regulatory
rs11742570	5	40410482	T>A,C,G	0.395	non_coding_transcript_exon_variant	RNU1-150P - TTC33	2e-82	Tier 4: intronic/intergenic
rs4410767	6	32480352	T>A,C,G	0.05	intron_variant	HLA-DRB9 - HLA-DRB5	2e-77	Tier 4: intronic/intergenic
rs4409764	10	99524480	T>A,G	0.05	intron_variant	LINC01475	3e-72	Tier 4: intronic/intergenic
rs9268557	6	32421528	T>A,C,G	0.05	intron_variant	TSBP1-AS1 - HLA-DRA	6e-71	Tier 4: intronic/intergenic
rs755374	5	159402286	C>A,G,T	0.05	intergenic_variant	IL12B-AS1	5e-67	Tier 4: intronic/intergenic
rs6880778	5	40398994	A>G	0.05	intergenic_variant	RNU1-150P - TTC33	5e-65	Tier 4: intronic/intergenic
rs10748781	10	99523573	C>A,G	0.05	non_coding_transcript_exon_variant	LINC01475	2e-63	Tier 4: intronic/intergenic
rs9271511	6	32621706	G>A	0.05	intron_variant	HLA-DRB1 - HLA-DQA1	4e-60	Tier 4: intronic/intergenic
rs113653754	6	32658495		0.27	intergenic_variant	HLA-DQA1 - HLA-DQB1	3e-58	Tier 4: intronic/intergenic
rs41268924	6	32167360	G>A,C	0.05	synonymous_variant	EGFL8, PPT2-EGFL8	4e-58	Tier 4: intronic/intergenic
rs10781499	9	136371953	G>A	0.412	synonymous_variant	CARD9	4e-56	Tier 4: intronic/intergenic
rs1131095	3	49676792	T>C,G	0.05	stop_gained	APEH	2e-55	Tier 1: coding
rs3024495	1	206769068	C>A,G,T	0.05	intron_variant	IL10	5e-55	Tier 4: intronic/intergenic
rs17212937	6	32713562	C>G,T	0.05	intergenic_variant	MTCO3P1 - HLA-DQB3	6e-55	Tier 4: intronic/intergenic
rs34236350	2	240628909	C>T	0.05	intron_variant	GPR35	8e-54	Tier 4: intronic/intergenic
rs4077515	9	136372044	C>A,G,T	0.05	missense_variant	CARD9	1e-53	Tier 1: coding
rs10761659	10	62685804	A>C,G	0.46	intron_variant	LINC02929 - ALDH7A1P4	5e-53	Tier 4: intronic/intergenic
rs2188962	5	132435113	C>T	0.425	intron_variant	CARINH	1e-52	Tier 4: intronic/intergenic
rs9836291	3	49660026	G>A	0.05	intron_variant	BSN	1e-52	Tier 4: intronic/intergenic
rs11236797	11	76588605	C>A	0.05	regulatory_region_variant	EMSY - LINC02757	9e-52	Tier 3: regulatory
rs3024493	1	206770623	C>A,G,T	0.05	intron_variant	IL10	2e-50	Tier 4: intronic/intergenic
rs56167332	5	159400761	C>A,T	0.338	intergenic_variant	IL12B-AS1	7e-50	Tier 4: intronic/intergenic
rs2836883	21	39094818	G>A	0.05	intergenic_variant	LINC02940 - RPL23AP12	3e-48	Tier 4: intronic/intergenic

ClinVar germline variants

135 retrieved; paginated sample, class counts are floors:

67 likely benign, 57 uncertain significance, 8 benign, 1 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1174126	NM_014439.4(IL37):c.530T>C (p.Ile177Thr)	IL37	Pathogenic	no assertion criteria provided
456662	NM_000572.3(IL10):c.43G>A (p.Gly15Arg)	LOC128462409	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3237528	NM_001631.5(ALPI):c.83C>T (p.Pro28Leu)	ALPI	Uncertain significance	criteria provided, single submitter
3237539	NM_001631.5(ALPI):c.406C>T (p.Arg136Cys)	ALPI	Uncertain significance	criteria provided, single submitter
1409891	NC_000001.10:g.(?206941981)(208391267_?)dup	C4BPA	Uncertain significance	criteria provided, single submitter
1004415	NM_000572.3(IL10):c.332C>T (p.Ser111Phe)	IL10	Uncertain significance	criteria provided, single submitter
1005651	NM_000572.3(IL10):c.343A>T (p.Asn115Tyr)	IL10	Uncertain significance	criteria provided, single submitter
1011995	NM_000572.3(IL10):c.370C>T (p.Arg124Trp)	IL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1025334	NM_000572.3(IL10):c.365G>A (p.Arg122Lys)	IL10	Uncertain significance	criteria provided, single submitter
1051340	NM_000572.3(IL10):c.100C>A (p.Pro34Thr)	IL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1056748	NM_000572.3(IL10):c.314T>G (p.Ile105Ser)	IL10	Uncertain significance	criteria provided, single submitter
1349359	NM_000572.3(IL10):c.534C>G (p.Asn178Lys)	IL10	Uncertain significance	criteria provided, single submitter
1367861	NM_000572.3(IL10):c.209T>A (p.Leu70Ter)	IL10	Uncertain significance	criteria provided, single submitter
1369972	NM_000572.3(IL10):c.383G>A (p.Arg128Gln)	IL10	Uncertain significance	criteria provided, single submitter
1399178	NM_000572.3(IL10):c.320C>T (p.Ala107Val)	IL10	Uncertain significance	criteria provided, single submitter
1409149	NM_000572.3(IL10):c.434C>T (p.Ala145Val)	IL10	Uncertain significance	criteria provided, single submitter
1420500	NM_000572.3(IL10):c.374G>A (p.Arg125His)	IL10	Uncertain significance	criteria provided, single submitter
1422156	NM_000572.3(IL10):c.502A>G (p.Ile168Val)	IL10	Uncertain significance	criteria provided, single submitter
1432945	NM_000572.3(IL10):c.371G>A (p.Arg124Gln)	IL10	Uncertain significance	criteria provided, single submitter
1441711	NM_000572.3(IL10):c.301C>A (p.Gln101Lys)	IL10	Uncertain significance	criteria provided, single submitter
1446386	NM_000572.3(IL10):c.444+6C>T	IL10	Uncertain significance	criteria provided, single submitter
1480748	NM_000572.3(IL10):c.225+6A>G	IL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1482256	NM_000572.3(IL10):c.374G>T (p.Arg125Leu)	IL10	Uncertain significance	criteria provided, single submitter
1484774	NM_000572.3(IL10):c.46G>T (p.Val16Leu)	IL10	Uncertain significance	criteria provided, single submitter
1488399	NM_000572.3(IL10):c.521T>C (p.Met174Thr)	IL10	Uncertain significance	criteria provided, single submitter
1493990	NM_000572.3(IL10):c.121C>T (p.Leu41Phe)	IL10	Uncertain significance	criteria provided, single submitter
1495514	NM_000572.3(IL10):c.241C>A (p.Gln81Lys)	IL10	Uncertain significance	criteria provided, single submitter
1522939	NM_000572.3(IL10):c.37C>A (p.Leu13Met)	IL10	Uncertain significance	criteria provided, single submitter
1525940	NM_000572.3(IL10):c.323A>G (p.His108Arg)	IL10	Uncertain significance	criteria provided, single submitter
1715483	NM_000572.3(IL10):c.424G>C (p.Val142Leu)	IL10	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 51 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 4

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
HSPA1L	HSPA1L	GWAS, GenCC
IL10	IL10	GWAS, Orphanet
IL19	IL19	GWAS
NKX2-3	NKX2-3	GWAS, GenCC

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DUOX2	Strong	Autosomal recessive	inflammatory bowel disease	5
SLCO2A1	Strong	Autosomal recessive	inflammatory bowel disease	10
ALPI	Moderate	Autosomal recessive	inflammatory bowel disease
HSPA1L	Moderate	Autosomal dominant	inflammatory bowel disease
FMNL2	Limited	Autosomal dominant	inflammatory bowel disease
NKX2-3	Limited	Autosomal dominant	inflammatory bowel disease
TLR4	Limited	Autosomal recessive	inflammatory bowel disease
TRIM22	Limited	Autosomal recessive	inflammatory bowel disease	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALPI	Orphanet:597887	ALPI-related inflammatory bowel disease
IL10	Orphanet:117	Behçet disease
IL10	Orphanet:238569	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome
IL10	Orphanet:536	Systemic lupus erythematosus
SLCO2A1	Orphanet:2796	Pachydermoperiostosis
SLCO2A1	Orphanet:468641	Chronic enteropathy associated with SLCO2A1 gene
TLR4	Orphanet:117	Behçet disease
DUOX2	Orphanet:226316	Genetic transient congenital hypothyroidism
DUOX2	Orphanet:95716	Familial thyroid dyshormonogenesis
TRIM22	Orphanet:597201	TRIM22-related inflammatory bowel disease
RIT1	Orphanet:648	Noonan syndrome
RORC	Orphanet:477857	Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
RPS14	Orphanet:86841	Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2
SEMA3E	Orphanet:138	CHARGE syndrome
SKIC2	Orphanet:84064	Trichohepatoenteric syndrome
SLC11A1	Orphanet:3389	Tuberculosis
SLC11A1	Orphanet:586	Cystic fibrosis
SLC22A5	Orphanet:158	Systemic primary carnitine deficiency
SLC34A1	Orphanet:157215	Hereditary hypophosphatemic rickets with hypercalciuria
SLC34A1	Orphanet:244305	Dominant hypophosphatemia with nephrolithiasis or osteoporosis
SLC34A1	Orphanet:300547	Autosomal recessive infantile hypercalcemia
SLC34A1	Orphanet:3337	Primary Fanconi renotubular syndrome
ZFP36L2	Orphanet:488191	Female infertility due to oocyte meiotic arrest
ZFP36L2	Orphanet:675396	Epithelioid hemangioma
SOX5	Orphanet:313884	12p12.1 microdeletion syndrome
SOX5	Orphanet:313892	Developmental and speech delay due to SOX5 deficiency
SOX5	Orphanet:626	Large/giant congenital melanocytic nevus
STAT1	Orphanet:319595	Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency
STAT1	Orphanet:391311	Susceptibility to viral and mycobacterial infections due to STAT1 deficiency
STAT1	Orphanet:391487	STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome
STAT3	Orphanet:2314	Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency
STAT3	Orphanet:438159	STAT3-related early-onset multisystem autoimmune disease
STAT3	Orphanet:512017	Chronic lymphoproliferative disorder of natural killer cells
STAT3	Orphanet:520	Acute promyelocytic leukemia
STAT3	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
STAT3	Orphanet:86872	T-cell large granular lymphocyte leukemia
STAT3	Orphanet:99885	Isolated permanent neonatal diabetes mellitus
STAT4	Orphanet:117	Behçet disease
STAT4	Orphanet:536	Systemic lupus erythematosus
STAT4	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
STAT4	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
STAT4	Orphanet:93552	Pediatric systemic lupus erythematosus
STAT5B	Orphanet:220465	Laron syndrome with immunodeficiency
STAT5B	Orphanet:520	Acute promyelocytic leukemia
STK11	Orphanet:2869	Peutz-Jeghers syndrome
BTNL2	Orphanet:797	Sarcoidosis
TCOF1	Orphanet:861	Treacher-Collins syndrome

Cohort genes → proteins

73 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	62
gwas_and_gencc	2
gwas_and_clinvar	2
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALPI	HGNC:437	ENSG00000163295	P09923	Intestinal-type alkaline phosphatase	gencc,clinvar
HSPA1L	HGNC:5234	ENSG00000204390	P34931	Heat shock 70 kDa protein 1-like	gwas,gencc
IL10	HGNC:5962	ENSG00000136634	P22301	Interleukin-10	gwas,clinvar
IL19	HGNC:5990	ENSG00000142224	Q9UHD0	Interleukin-19	gwas,clinvar
NKX2-3	HGNC:7836	ENSG00000119919	Q8TAU0	Homeobox protein Nkx-2.3	gwas,gencc
SLCO2A1	HGNC:10955	ENSG00000174640	Q92959	Solute carrier organic anion transporter family member 2A1	gencc
TLR4	HGNC:11850	ENSG00000136869	O00206	Toll-like receptor 4	gencc
DUOX2	HGNC:13273	ENSG00000140279	Q9NRD8	Dual oxidase 2	gencc
TRIM22	HGNC:16379	ENSG00000132274	Q8IYM9	E3 ubiquitin-protein ligase TRIM22	gencc
FMNL2	HGNC:18267	ENSG00000157827	Q96PY5	Formin-like protein 2	gencc
RIT1	HGNC:10023	ENSG00000143622	Q92963	GTP-binding protein Rit1	gwas
RNF5	HGNC:10068	ENSG00000204308	Q99942	E3 ubiquitin-protein ligase RNF5	gwas
RORC	HGNC:10260	ENSG00000143365	P51449	Nuclear receptor ROR-gamma	gwas
RPL3	HGNC:10332	ENSG00000100316	P39023	Large ribosomal subunit protein uL3	gwas
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	gwas
RPS14	HGNC:10387	ENSG00000164587	P62263	Small ribosomal subunit protein uS11	gwas
RPS6KA2	HGNC:10431	ENSG00000071242	Q15349	Ribosomal protein S6 kinase alpha-2	gwas
RPS6KA4	HGNC:10433	ENSG00000162302	O75676	Ribosomal protein S6 kinase alpha-4	gwas
RPS6KB1	HGNC:10436	ENSG00000108443	P23443	Ribosomal protein S6 kinase beta-1	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
SCAMP3	HGNC:10565	ENSG00000116521	O14828	Secretory carrier-associated membrane protein 3	gwas
CXCR5	HGNC:1060	ENSG00000160683	P32302	C-X-C chemokine receptor type 5	gwas
SCNN1D	HGNC:10601	ENSG00000162572	P51172	Epithelial sodium channel subunit delta	gwas
CCL11	HGNC:10610	ENSG00000172156	P51671	Eotaxin	gwas
CCL13	HGNC:10611	ENSG00000181374	Q99616	C-C motif chemokine 13	gwas
CCL2	HGNC:10618	ENSG00000108691	P13500	C-C motif chemokine 2	gwas
CCL20	HGNC:10619	ENSG00000115009	P78556	C-C motif chemokine 20	gwas
CCL7	HGNC:10634	ENSG00000108688	P80098	C-C motif chemokine 7	gwas
CXCL5	HGNC:10642	ENSG00000163735	P42830	C-X-C motif chemokine 5	gwas
CXCL6	HGNC:10643	ENSG00000124875	P80162	C-X-C motif chemokine 6	gwas
ENTR1	HGNC:10667	ENSG00000165689	Q96C92	Endosome-associated-trafficking regulator 1	gwas
SDF2L1	HGNC:10676	ENSG00000128228	Q9HCN8	Stromal cell-derived factor 2-like protein 1	gwas
SELE	HGNC:10718	ENSG00000007908	P16581	E-selectin	gwas
SELL	HGNC:10720	ENSG00000188404	P14151	L-selectin	gwas
SELP	HGNC:10721	ENSG00000174175	P16109	P-selectin	gwas
SEMA3E	HGNC:10727	ENSG00000170381	O15041	Semaphorin-3E	clinvar
SHC1	HGNC:10840	ENSG00000160691	P29353	SHC-transforming protein 1	gwas
SKIC2	HGNC:10898	ENSG00000204351	Q15477	Superkiller complex protein 2	gwas
SLAMF1	HGNC:10903	ENSG00000117090	Q13291	Signaling lymphocytic activation molecule	gwas
SLC11A1	HGNC:10907	ENSG00000018280	P49279	Natural resistance-associated macrophage protein 1	gwas
SLC22A4	HGNC:10968	ENSG00000197208	Q9H015	Solute carrier family 22 member 4	gwas
SLC22A5	HGNC:10969	ENSG00000197375	O76082	Organic cation/carnitine transporter 2	gwas
BRAP	HGNC:1099	ENSG00000089234	Q7Z569	BRCA1-associated protein	gwas
SLC34A1	HGNC:11019	ENSG00000131183	Q06495	Sodium-dependent phosphate transport protein 2A	gwas
BRD2	HGNC:1103	ENSG00000204256	P25440	Bromodomain-containing protein 2	gwas
SLC6A7	HGNC:11054	ENSG00000011083	Q99884	Sodium-dependent proline transporter	gwas
BABAM2	HGNC:1106	ENSG00000158019	Q9NXR7	BRISC and BRCA1-A complex member 2	gwas
ZFP36L1	HGNC:1107	ENSG00000185650	Q07352	mRNA decay activator protein ZFP36L1	gwas
SLC9A4	HGNC:11077	ENSG00000180251	Q6AI14	Sodium/hydrogen exchanger 4	gwas
ZFP36L2	HGNC:1108	ENSG00000152518	P47974	mRNA decay activator protein ZFP36L2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALPI	Intestinal-type alkaline phosphatase	Alkaline phosphatase that can hydrolyze various phosphate compounds.
HSPA1L	Heat shock 70 kDa protein 1-like	Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the form…
IL10	Interleukin-10	Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
IL19	Interleukin-19	Cytokine that functions as an anti-inflammatory and proangiogenic factor.
NKX2-3	Homeobox protein Nkx-2.3	Transcription factor.
SLCO2A1	Solute carrier organic anion transporter family member 2A1	Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane.
TLR4	Toll-like receptor 4	Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways.
DUOX2	Dual oxidase 2	Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO.
TRIM22	E3 ubiquitin-protein ligase TRIM22	Interferon-induced E3 ubiquitin ligase that plays important roles in innate and adaptive immunity.
FMNL2	Formin-like protein 2	Plays a role in the regulation of cell morphology and cytoskeletal organization.
RIT1	GTP-binding protein Rit1	Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
RNF5	E3 ubiquitin-protein ligase RNF5	Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins.
RORC	Nuclear receptor ROR-gamma	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
RPL3	Large ribosomal subunit protein uL3	Component of the large ribosomal subunit.
CFB	Complement factor B	Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
RPS14	Small ribosomal subunit protein uS11	Component of the small ribosomal subunit.
RPS6KA2	Ribosomal protein S6 kinase alpha-2	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, su…
RPS6KA4	Ribosomal protein S6 kinase alpha-4	Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation…
RPS6KB1	Ribosomal protein S6 kinase beta-1	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression.
ATXN2	Ataxin-2	Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
SCAMP3	Secretory carrier-associated membrane protein 3	Functions in post-Golgi recycling pathways.
CXCR5	C-X-C chemokine receptor type 5	Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC).
SCNN1D	Epithelial sodium channel subunit delta	Potential alternative pore-forming subunit of the epithelial sodium channel (ENaC), capable of replacing the alpha/SCNN1A subunit, creating a more active channel with distinct properties.
CCL11	Eotaxin	Chemokine that plays a central role in both allergic and non-allergic inflammatory reactions by inducing the migration of different leukocyte types including eosinophils, basophils, macrophages and dendritic cells.
CCL13	C-C motif chemokine 13	Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils, but not neutrophils.
CCL2	C-C motif chemokine 2	Acts as a ligand for C-C chemokine receptor CCR2.
CCL20	C-C motif chemokine 20	Acts as a ligand for C-C chemokine receptor CCR6.
CCL7	C-C motif chemokine 7	Chemotactic factor that plays an important role in immune regulation.
CXCL5	C-X-C motif chemokine 5	Involved in neutrophil activation.
CXCL6	C-X-C motif chemokine 6	Chemotactic for neutrophil granulocytes.
ENTR1	Endosome-associated-trafficking regulator 1	Endosome-associated protein that plays a role in membrane receptor sorting, cytokinesis and ciliogenesis.
SELE	E-selectin	Cell-surface glycoprotein having a role in immunoadhesion.
SELL	L-selectin	Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells.
SELP	P-selectin	Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes.
SEMA3E	Semaphorin-3E	Plays an important role in signaling via the cell surface receptor PLXND1.
SHC1	SHC-transforming protein 1	Signaling adapter that couples activated growth factor receptors to signaling pathways.
SKIC2	Superkiller complex protein 2	Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways.
SLAMF1	Signaling lymphocytic activation molecule	Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family.
SLC11A1	Natural resistance-associated macrophage protein 1	Macrophage-specific antiporter that fluxes metal ions in either direction against a proton gradient.
SLC22A4	Solute carrier family 22 member 4	Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations.
SLC22A5	Organic cation/carnitine transporter 2	Sodium-ion dependent, high affinity carnitine transporter.
BRAP	BRCA1-associated protein	Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein.
SLC34A1	Sodium-dependent phosphate transport protein 2A	Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.
BRD2	Bromodomain-containing protein 2	Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at ‘Lys-5’ and ‘Lys-12’ (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures.
SLC6A7	Sodium-dependent proline transporter	Brain specific sodium (and chloride)-dependent proline transporter.
BABAM2	BRISC and BRCA1-A complex member 2	Component of the BRCA1-A complex, a complex that specifically recognizes ‘Lys-63’-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks…
ZFP36L1	mRNA decay activator protein ZFP36L1	Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthes…
SLC9A4	Sodium/hydrogen exchanger 4	Electroneutral antiporter that exchanges sodium for protons or ammonium ions at the basolateral membrane of epithelia to regulate cell volume and intracellular pH upon hypertonic conditions.
ZFP36L2	mRNA decay activator protein ZFP36L2	Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthes…
SNAPC4	snRNA-activating protein complex subunit 4	Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes.

Protein-family classification

Druggable: 20 · Difficult: 17 · Unknown: 36 · Druggable fraction: 0.27

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Complement	3	11.0×	0.031
Transcription factor	16	1.8×	0.076
Transporter	3	3.2×	0.271
Nuclear receptor	1	5.3×	0.519
Kinase	4	1.5×	0.647
Antibody/Immunoglobulin	3	1.2×	0.918
Phosphatase	1	1.1×	0.987
Other/Unknown	36	0.9×	0.987
Protease	1	0.5×	0.987
Enzyme (other)	3	0.5×	0.987
GPCR	1	0.3×	0.987
Scaffold/PPI	1	0.2×	0.987

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALPI	Phosphatase	yes		Alkaline_phosphatase, Alkaline_phosphatase_core_sf, Alkaline_phosphatase_AS
HSPA1L	Other/Unknown	no		Hsp_70_fam, Heat_shock_70_CS, HSP70_peptide-bd_sf
IL10	Other/Unknown	no		IL-10, 4_helix_cytokine-like_core, IL-10_CS
IL19	Other/Unknown	no		4_helix_cytokine-like_core, IL-19, IL-10_CS
NKX2-3	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
SLCO2A1	Transporter	yes		Kazal_dom, OATP, MFS_dom
TLR4	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
DUOX2	Enzyme (other)	yes	1.6.3.1	EF_hand_dom, Haem_peroxidase_sf, EF-hand-dom_pair
TRIM22	Transcription factor	no	2.3.2.27	Znf_B-box, Znf_RING, B30.2/SPRY
FMNL2	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-like
RIT1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
RNF5	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
RORC	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RPL3	Other/Unknown	no		Ribosomal_uL3, Transl_B-barrel_sf, Ribosomal_uL3_CS
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
RPS14	Other/Unknown	no		Ribosomal_uS11, Ribosomal_uS11_CS, Ribosomal_uS11_sf
RPS6KA2	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
RPS6KA4	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
RPS6KB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf
SCAMP3	Other/Unknown	no		SCAMP
CXCR5	GPCR	yes		GPCR_Rhodpsn, Chemokine_CXCR5, GPCR_Rhodpsn_7TM
SCNN1D	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
CCL11	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
CCL13	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
CCL2	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
CCL20	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Chemokine_CC_DCCL
CCL7	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
CXCL5	Other/Unknown	no		Chemokine_CXC, Chemokine_IL8-like_dom, Chemokine_CXC_CS
CXCL6	Other/Unknown	no		Chemokine_CXC, Chemokine_IL8-like_dom, Chemokine_CXC_CS
ENTR1	Other/Unknown	no		ENTR1
SDF2L1	Other/Unknown	no		MIR_motif, MIR_dom_sf
SELE	Complement	yes		Sushi_SCR_CCP_dom, EGF, C-type_lectin-like
SELL	Complement	yes		Sushi_SCR_CCP_dom, EGF, C-type_lectin-like
SELP	Complement	yes		Sushi_SCR_CCP_dom, EGF, C-type_lectin-like
SEMA3E	Antibody/Immunoglobulin	yes		Semap_dom, Ig-like_dom, Immunoglobulin_dom
SHC1	Scaffold/PPI	no		SH2, PID_Shc-like, PTB/PI_dom
SKIC2	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Ski2/MTR4_C
SLAMF1	Antibody/Immunoglobulin	yes		Ig-like_dom, Sig_lymph_act_molc_N, Ig-like_fold
SLC11A1	Other/Unknown	no		NRAMP_fam
SLC22A4	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC22A5	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
BRAP	Transcription factor	no		Znf_UBP, Znf_RING, BRAP2/ETP1_RRM
SLC34A1	Other/Unknown	no		Na/Pi_transpt
BRD2	Other/Unknown	no		Bromodomain, Bromodomain_CS, NET_dom
SLC6A7	Other/Unknown	no		Na/ntran_symport, SNS_sf
BABAM2	Other/Unknown	no		BRE
ZFP36L1	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf
SLC9A4	Other/Unknown	no		NHE-2/4, NaH_exchanger, Cation/H_exchanger_TM
ZFP36L2	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf

Expression context

Cohort genes with no expression data: 0.

63 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	73
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	7
gall bladder	6
leukocyte	6
mononuclear cell	6
right lobe of liver	6
granulocyte	6
left testis	5
right testis	5
right hemisphere of cerebellum	5
mucosa of transverse colon	5
cerebellar hemisphere	4
right adrenal gland	4
cartilage tissue	3
spleen	3
cortical plate	3
male germ line stem cell (sensu Vertebrata) in testis	3
type B pancreatic cell	3
cerebellar cortex	3
calcaneal tendon	3
endothelial cell	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALPI	41	tissue_specific	marker	jejunal mucosa, duodenum, ileal mucosa
HSPA1L	130	tissue_specific	yes	left testis, right testis, testis
IL10	158	broad	marker	vermiform appendix, gall bladder, cartilage tissue
IL19	111	broad	marker	nasal cavity epithelium, mucosa of stomach, nasal cavity mucosa
NKX2-3	69	tissue_specific	yes	muscle layer of sigmoid colon, spleen, small intestine Peyer’s patch
SLCO2A1	252	broad	marker	right lung, upper lobe of left lung, upper lobe of lung
TLR4	233	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
DUOX2	191	tissue_specific	marker	gall bladder, nasal cavity epithelium, palpebral conjunctiva
TRIM22	285	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
FMNL2	262	ubiquitous	marker	inferior vagus X ganglion, corpus callosum, subthalamic nucleus
RIT1	268	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
RNF5	134	ubiquitous	marker	ganglionic eminence, adult mammalian kidney, cortical plate
RORC	209	broad	marker	gastrocnemius, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
RPL3	307	ubiquitous	marker	left ovary, right ovary, type B pancreatic cell
CFB	134	broad	marker	right lobe of liver, liver, gall bladder
RPS14	305	ubiquitous	marker	upper leg skin, adult organism, skin of hip
RPS6KA2	295	ubiquitous	marker	inferior olivary complex, lower lobe of lung, medial globus pallidus
RPS6KA4	215	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
RPS6KB1	275	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, calcaneal tendon
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
SCAMP3	143	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
CXCR5	172	tissue_specific	marker	granulocyte, spleen, lymph node
SCNN1D	161	ubiquitous	yes	right hemisphere of cerebellum, right testis, left testis
CCL11	128	broad	marker	pylorus, cardia of stomach, caecum
CCL13	174	tissue_specific	yes	primordial germ cell in gonad, mucosa of transverse colon, decidua
CCL2	252	ubiquitous	marker	vena cava, gall bladder, islet of Langerhans
CCL20	202	broad	marker	epithelium of nasopharynx, cartilage tissue, gall bladder
CCL7	124	broad	yes	frontal pole, type B pancreatic cell, paraflocculus
CXCL5	173	broad	marker	monocyte, mononuclear cell, leukocyte
CXCL6	186	broad	marker	bronchial epithelial cell, palpebral conjunctiva, spleen

Protein interactions among cohort

Intra-cohort edges: 36.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT3	10,108
RPL3	6,978
TLR4	6,974
STAT1	6,459
IL10	6,185
CCL2	5,749
RPS6KB1	5,474
STK11	5,146
HSPA1L	4,397
STAT5A	4,153

Intra-cohort edges

A	B	Sources
BABAM2	BRAP	string_interaction
BTNL2	HSPA1L	string_interaction
BTNL2	SLC11A1	string_interaction
CCL11	CCL13	biogrid_interaction, intact
CCL11	CCL2	biogrid_interaction, intact
CCL11	CXCL5	biogrid_interaction, intact
CCL11	CXCL6	biogrid_interaction, intact
CCL13	CCL2	biogrid_interaction, string_interaction
CCL13	CXCL6	string_interaction
CCL13	IL10	string_interaction
CCL2	CCL20	string_interaction
CCL20	CXCL5	biogrid_interaction, intact
CCL7	CXCL6	biogrid_interaction, intact
CXCL6	IL10	string_interaction
ENTR1	NKX2-3	string_interaction
ENTR1	SLC9A4	string_interaction
IL10	IL19	string_interaction
IL10	IL24	string_interaction
IL19	STAT3	string_interaction
IL24	STAT3	string_interaction
NKX2-3	SLC9A4	string_interaction
RNF5	SSR2	string_interaction
SELE	SELL	biogrid_interaction
SELL	SELP	string_interaction
SKIC2	WHR1	string_interaction
SLC11A1	SLC34A1	string_interaction
SLC22A4	SLC22A5	intact
STAT1	STAT3	intact, string_interaction
STAT1	STAT4	biogrid_interaction, intact, string_interaction
STAT1	STAT5A	biogrid_interaction
STAT1	STAT5B	string_interaction
STAT3	STAT5A	string_interaction
STAT3	STAT5B	biogrid_interaction, string_interaction
STAT3	TRIM22	intact
STAT5A	STAT5B	intact
SULT1A1	SULT1A2	biogrid_interaction, intact

Structural data

PDB: 49 · AlphaFold-only: 24 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS14	P62263	213
RPL3	P39023	193
BRD2	P25440	174
RORC	P51449	161
CFB	P00751	26
RPS6KB1	P23443	22
SNAPC4	Q5SXM2	18
SELE	P16581	17
TLR4	O00206	15
CCL2	P13500	14
SHC1	P29353	11
SKIC2	Q15477	11
SULT1A1	P50225	11
CCL7	P80098	10
STAT1	P42224	10
IL10	P22301	9
SLCO2A1	Q92959	7
SLC6A7	Q99884	7
CCL20	P78556	6
SLAMF1	Q13291	6
STAT3	P40763	6
SELP	P16109	5
STAT5A	P42229	5
WHR1	P49842	5
CCL11	P51671	4
BABAM2	Q9NXR7	4
STK11	Q15831	4
RIT1	Q92963	3
CXCL5	P42830	3
SELL	P14151	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALPI	P09923	93.46
SDF2L1	Q9HCN8	89.30
STAT4	Q14765	86.87
BTNL2	Q9UIR0	85.97
THBS3	P49746	85.66
TRIM22	Q8IYM9	85.38
SLC22A4	Q9H015	85.07
SEMA3E	O15041	84.62
DUOX2	Q9NRD8	84.37
CXCR5	P32302	80.85
RPS6KA2	Q15349	77.37
SCAMP3	O14828	76.99
BRAP	Q7Z569	76.92
SLC34A1	Q06495	72.24
RPS6KA4	O75676	72.00
RNF5	Q99942	68.71
SLC9A4	Q6AI14	66.73
TCTA	P57738	66.03
ENTR1	Q96C92	65.28
TCF19	Q9Y242	63.17
NKX2-3	Q8TAU0	60.75
SOX5	P35711	58.95
TCOF1	Q13428	41.78
BSN	Q9UPA5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 733. Enrichment computed across 250 evidence-associated genes (173 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 173 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-20 family signaling	10	24.4×	2e-09	IL19, IL24, STAT1, STAT3, STAT4, STAT5A, STAT5B, TYK2 (+2 more)
Chemokine receptors bind chemokines	13	14.1×	2e-09	CXCR5, CCL11, CCL13, CCL2, CCL20, CCL7, CXCL5, CXCL6 (+5 more)
Signaling by Interleukins	17	6.3×	4e-07	RORC, RPS6KA2, CCL11, CCL2, CCL20, SHC1, STAT1, STAT3 (+9 more)
Interleukin-10 signaling	9	12.1×	7e-06	IL10, CCL2, CCL20, STAT3, TNF, TYK2, CCR1, CCR2 (+1 more)
Cytokine Signaling in Immune system	19	4.5×	7e-06	RORC, RPS6KA2, CCL11, CCL2, CCL20, SHC1, STAT1, STAT3 (+11 more)
FGFR1 mutant receptor activation	5	33.0×	2e-05	STAT1, STAT3, STAT5A, STAT5B, CEP43
Interleukin-21 signaling	5	33.0×	2e-05	STAT1, STAT3, STAT4, STAT5A, STAT5B
Interleukin-2 family signaling	6	22.0×	2e-05	SHC1, STAT1, STAT3, STAT4, STAT5A, STAT5B
TNFs bind their physiological receptors	7	15.9×	2e-05	TNFRSF14, TNFRSF18, TNFRSF4, TNFRSF6B, TNFRSF9, TNFSF15, TNFSF8
Signaling by CSF3 (G-CSF)	6	19.8×	3e-05	SHC1, STAT1, STAT3, STAT5A, STAT5B, TYK2
Immune System	32	2.4×	2e-04	RORC, RPS6KA2, CCL11, CCL2, CCL20, SELL, SHC1, STAT1 (+24 more)
Signaling by cytosolic FGFR1 fusion mutants	5	18.3×	3e-04	STAT1, STAT3, STAT5A, STAT5B, CEP43
Interleukin-9 signaling	4	29.3×	3e-04	STAT1, STAT3, STAT5A, STAT5B
Signaling by KIT in disease	4	26.4×	5e-04	STAT1, STAT3, STAT5A, STAT5B
Diseases of signal transduction by growth factor receptors and second messengers	13	4.3×	6e-04	SHC1, BRAP, STAT1, STAT3, STAT5A, STAT5B, CAMK2A, CD19 (+5 more)
Signaling by ALK fusions and activated point mutants	8	7.0×	8e-04	IL10, SHC1, STAT1, STAT3, STAT5A, TYK2, IL22, CEBPB
Interleukin-35 Signalling	4	22.0×	9e-04	STAT1, STAT3, STAT4, TYK2
Peptide ligand-binding receptors	11	4.7×	9e-04	CCL11, CCL13, CCL2, CCL20, CCL7, UTS2, CCR1, CCR2 (+3 more)
Inactivation of CSF3 (G-CSF) signaling	5	12.7×	0.001	STAT1, STAT3, STAT5A, STAT5B, TYK2
G alpha (i) signalling events	15	3.4×	0.001	CXCR5, CCL13, CCL20, CXCL5, CXCL6, GPSM3, CAMK2A, RXFP4 (+7 more)
Signaling by FGFR in disease	5	12.2×	0.002	STAT1, STAT3, STAT5A, STAT5B, CEP43
Interleukin-15 signaling	4	17.6×	0.002	SHC1, STAT3, STAT5A, STAT5B
Unfolded Protein Response (UPR)	5	10.3×	0.003	CCL2, SHC1, MYDGF, CEBPB, CEBPG
Class A/1 (Rhodopsin-like receptors)	10	4.3×	0.004	CCL11, CCL13, CCL2, CCL20, CCL7, CCR1, CCR2, CCR3 (+2 more)
TNFR1-induced NF-kappa-B signaling pathway	5	9.7×	0.004	TNF, TNFAIP3, USP4, TAB2, TAB1
Signal Transduction	33	1.9×	0.004	RPS6KA2, RPS6KB1, CCL11, CCL13, CCL2, CCL20, CCL7, SHC1 (+25 more)
NOD1/2 Signaling Pathway	5	9.2×	0.005	TNFAIP3, CARD9, TAB2, AAMP, TAB1
Activation of C3 and C5	3	22.0×	0.007	CFB, C2, C4A
Interleukin-23 signaling	3	22.0×	0.007	STAT3, STAT4, TYK2
Signaling by FGFR1 in disease	5	8.5×	0.007	STAT1, STAT3, STAT5A, STAT5B, CEP43

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 231 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
inflammatory response	31	5.1×	2e-10	RPS6KA4, CCL11, CCL13, CCL2, CCL20, CCL7, CXCL5, CXCL6 (+23 more)
immune response	26	5.3×	4e-09	IL10, IL19, CXCR5, CCL20, SLAMF1, IL24, TLR4, TNF (+18 more)
cell surface receptor signaling pathway via JAK-STAT	10	12.6×	3e-06	CCL2, STAT1, STAT3, STAT4, STAT5A, STAT5B, TNF, CD40 (+2 more)
chemotaxis	13	7.7×	7e-06	CCL11, CCL13, CCL2, CCL20, CCL7, CXCL5, CXCL6, FOSL1 (+5 more)
defense response	10	9.3×	3e-05	STAT1, STAT3, STAT4, STAT5A, STAT5B, DUOX2, CD48, TNIP1 (+2 more)
cellular response to lipopolysaccharide	14	5.9×	3e-05	IL10, CCL2, CXCL5, CXCL6, IL24, TLR4, TNF, TNFAIP3 (+6 more)
cytokine-mediated signaling pathway	12	6.8×	5e-05	CCL2, STAT3, STAT4, STAT5A, STAT5B, TYK2, DUOX2, FOSL1 (+4 more)
chemokine-mediated signaling pathway	8	11.2×	1e-04	CCL11, CCL13, CCL2, CCL7, CXCL6, CCR1, CCR2, CCR3
positive regulation of inflammatory response	11	6.9×	1e-04	CCL7, STAT3, STAT5A, STAT5B, TLR4, TNF, GPSM3, CCR1 (+3 more)
positive regulation of type II interferon production	9	8.8×	1e-04	SLAMF1, SLC11A1, TLR4, TNF, TYK2, CCR2, CD226, CD244 (+1 more)
Peyer’s patch development	4	36.5×	4e-04	NKX2-3, RORC, STAT5A, STAT5B
positive regulation of cytokine production involved in inflammatory response	6	14.1×	5e-04	STAT3, TLR4, TNF, GPSM3, CARD9, CD6
negative regulation of interleukin-6 production	7	10.6×	5e-04	IL10, SLAMF1, TLR4, TNF, TNFAIP3, IL37, BANK1
calcium-mediated signaling	9	7.1×	6e-04	CXCR5, CCL20, SELE, TNF, CCR1, CCR2, CCR3, CCR5 (+1 more)
growth hormone receptor signaling pathway via JAK-STAT	4	26.5×	0.001	STAT3, STAT5A, STAT5B, TYK2
cellular response to type II interferon	8	7.2×	0.002	RPS6KB1, CCL2, STAT1, TLR4, TNF, VAMP3, SLC26A6, CAMK2A
positive regulation of canonical NF-kappaB signal transduction	13	4.1×	0.002	STAT3, TLR4, TNF, CD40, TNFSF15, TRAF3IP2, TRIM22, CARD9 (+5 more)
response to bacterium	8	6.7×	0.003	RNF5, CFB, CCL2, SLC11A1, C2, IKZF3, ERAP1, BANK1
cell chemotaxis	8	6.4×	0.003	CXCR5, CCL11, CCL20, CCR1, CCR2, CCR3, CCR5, CCR6
dendritic cell chemotaxis	4	17.2×	0.006	CCR1, CCR2, CCR5, CCR6
response to type II interferon	5	11.4×	0.006	SLC11A1, SLC22A5, STAT1, CD40, CD74
regulation of steroid metabolic process	3	31.3×	0.006	RORC, STAT5A, STAT5B
positive regulation of apoptotic cell clearance	3	31.3×	0.006	CCL2, C2, C4A
cellular defense response	6	8.3×	0.006	FOSL1, FCMR, CCR2, CCR3, CCR5, CCR6
response to lipopolysaccharide	9	4.9×	0.007	SELE, SELP, SLC11A1, SLC22A4, TLR4, C2, TRIB1, CD6 (+1 more)
phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	6.4×	0.008	ZFP36L1, STAT3, TNF, CD40, CD28, ERRFI1, BANK1
leukocyte cell-cell adhesion	5	10.1×	0.008	SELE, SELL, SELP, F11R, TNIP1
positive regulation of interleukin-2 production	5	10.1×	0.008	STAT5A, STAT5B, BTNL2, CCR2, CD28
interleukin-9-mediated signaling pathway	3	27.4×	0.008	STAT1, STAT3, STAT5A
regulatory T cell differentiation	3	27.4×	0.008	RORC, ZBTB46, CD28

Therapeutics

Drugs indicated for this disease

0 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Adalimumab	Phase 3 (in late-stage trials)
Brazikumab	Phase 3 (in late-stage trials)
Charcoal, Activated	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Fluconazole	Phase 3 (in late-stage trials)
IRON ISOMALTOSIDE 1000	Phase 3 (in late-stage trials)
Infliximab	Phase 3 (in late-stage trials)
Mirikizumab	Phase 3 (in late-stage trials)
Ustekinumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Amitriptyline, Atorvastatin, Budesonide, Dapagliflozin, Etrasimod, Fenofibrate, Filgotinib, Hydrocortisone, Mesalamine, Metformin, Minocycline, Nifuroxazide, Pentoxifylline, Rosiglitazone, Secukinumab, Vidofludimus.

Drug target analysis

Approved (phase 4): 16 · Phase ≥3: 20 · Phased (≥1): 24 · Undrugged: 49

Druggability breadth: 117 of 250 evidence-associated genes (47%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ALPI	LEVAMISOLE
SLCO2A1	DINOPROST
TLR4	METHOTREXATE
RORC	DIGOXIN
RPL3	GENTAMICIN SULFATE
CFB	IPTACOPAN
RPS14	GENTAMICIN SULFATE
RPS6KA2	FEDRATINIB
RPS6KA4	FEDRATINIB
RPS6KB1	FEDRATINIB
SLC34A1	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS
STAT1	FILGOTINIB
STAT3	MOMELOTINIB
STAT5A	MOMELOTINIB
STK11	FEDRATINIB
SULT1A1	ESTRADIOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS6KB1	39	4
RPS6KA4	34	4
RPS6KA2	29	4
STAT3	18	4
STK11	17	4
RORC	9	4
BRD2	9	3
TLR4	6	4
ALPI	5	4
STAT1	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEVAMISOLE	4	ALPI
DINOPROST	4	SLCO2A1
METHOTREXATE	4	TLR4
POLYMYXIN B	4	TLR4
CARVEDILOL	4	TLR4
DIGOXIN	4	RORC, STAT3
TRETINOIN	4	RORC
ALITRETINOIN	4	RORC
GENTAMICIN SULFATE	4	RPL3, RPS14
IPTACOPAN	4	CFB
FEDRATINIB	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
RUXOLITINIB	4	RPS6KA2, RPS6KA4
NERATINIB	4	RPS6KA2
TOFACITINIB CITRATE	4	RPS6KA2
TOFACITINIB	4	RPS6KA2
BOSUTINIB	4	RPS6KA2, RPS6KB1
BRIGATINIB	4	RPS6KA2
NINTEDANIB	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
SUNITINIB	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
MIDOSTAURIN	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
ERLOTINIB	4	RPS6KA4
GEFITINIB	4	RPS6KA4
SORAFENIB	4	RPS6KB1
VANDETANIB	4	RPS6KB1
CRIZOTINIB	4	RPS6KB1
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
FILGOTINIB	4	STAT1
DEUCRAVACITINIB	4	STAT1, STAT3
MOMELOTINIB	4	STAT3, STAT5A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
STAT3	1,319	Binding:1304, Functional:12, Unclassified:2, ADMET:1
RORC	758	Binding:707, Functional:50, Unclassified:1
BRD2	681	Binding:655, Functional:19, ADMET:7
RPS6KB1	585	Binding:582, Functional:2, ADMET:1
RPS6KA2	448	Binding:446, ADMET:1, Functional:1
RPS6KA4	389	Binding:387, Functional:1, ADMET:1
TLR4	267	Binding:254, Functional:10, ADMET:3
STK11	244	Binding:244
STAT5A	199	Binding:199
STAT1	147	Binding:137, Functional:8, Unclassified:2
SELE	118	Binding:108, Functional:10
SELP	100	Binding:96, Functional:4
SLC22A5	97	Functional:79, ADMET:18
RPL3	90	Binding:90
RPS14	90	Binding:90
STAT5B	55	Binding:55
WHR1	36	Binding:36
CFB	33	Binding:33
CXCR5	33	Binding:21, Functional:12
SLC22A4	29	Functional:26, ADMET:3
CCL2	24	Binding:24
ALPI	21	Binding:12, Functional:6, ADMET:3
STAT4	20	Binding:20
SULT1A1	19	ADMET:15, Binding:4
SELL	16	Binding:16
SHC1	10	Binding:10
SLC34A1	8	Binding:7, Functional:1
TCOF1	8	Binding:8
SNAPC4	6	Binding:6
ATXN2	5	Binding:3, Functional:2
SLCO2A1	4	Functional:4
RNF5	2	Binding:2
CCL7	2	Binding:2
BRAP	2	Binding:2
SLC6A7	2	Binding:2
HSPA1L	1	Binding:1
DUOX2	1	Binding:1
SCAMP3	1	Binding:1
CCL11	1	Binding:1
SLC11A1	1	Binding:1
SULT1A2	1	ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DUOX2	1.6.3.1	NAD(P)H oxidase (H2O2-forming)
TRIM22	2.3.2.27	RING-type E3 ubiquitin transferase
CFB	3.4.21.47	alternative-complement-pathway C3/C5 convertase
RPS6KA2	2.7.11.1	non-specific serine/threonine protein kinase
RPS6KB1	2.7.11.1	non-specific serine/threonine protein kinase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
SULT1A1	2.8.2.1, 2.8.2.2	aryl sulfotransferase, alcohol sulfotransferase
SULT1A2	2.8.2.1, 2.8.2.2, 2.8.2.9	aryl sulfotransferase, alcohol sulfotransferase, tyrosine-ester sulfotransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TLR4	267
RORC	758
RPS6KA2	448
RPS6KA4	389
RPS6KB1	585
SELE	118
SELP	100
BRD2	681
STAT1	147
STAT3	1,319
STAT5A	199
STK11	244

Pharmacogenomics

Cohort genes with a PharmGKB record: 73; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LEVAMISOLE	4	ALPI
DINOPROST	4	SLCO2A1
METHOTREXATE	4	TLR4
POLYMYXIN B	4	TLR4
CARVEDILOL	4	TLR4
DIGOXIN	4	RORC, STAT3
TRETINOIN	4	RORC
ALITRETINOIN	4	RORC
GENTAMICIN SULFATE	4	RPL3, RPS14
IPTACOPAN	4	CFB
FEDRATINIB	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
RUXOLITINIB	4	RPS6KA2, RPS6KA4
NERATINIB	4	RPS6KA2
TOFACITINIB CITRATE	4	RPS6KA2
TOFACITINIB	4	RPS6KA2
BOSUTINIB	4	RPS6KA2, RPS6KB1
BRIGATINIB	4	RPS6KA2
NINTEDANIB	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
SUNITINIB	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
MIDOSTAURIN	4	RPS6KA2, RPS6KA4, RPS6KB1, STK11
ERLOTINIB	4	RPS6KA4
GEFITINIB	4	RPS6KA4
SORAFENIB	4	RPS6KB1
VANDETANIB	4	RPS6KB1
CRIZOTINIB	4	RPS6KB1
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
FILGOTINIB	4	STAT1
MOMELOTINIB	4	STAT3, STAT5A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	16	ALPI, SLCO2A1, TLR4, RORC, RPL3, CFB, RPS14, RPS6KA2, RPS6KA4, RPS6KB1 (+6 more)
B	Phased (≥1) drug, not yet approved	8	CCL2, SELE, SELL, SELP, BRD2, SNAPC4, STAT5B, TCOF1
C	Druggable family + PDB, no drug	3	SLAMF1, SLC22A5, SULT1A2
D	Druggable family + AlphaFold only, no drug	5	DUOX2, CXCR5, SEMA3E, SLC22A4, BTNL2
E	Difficult family or no structure, no drug	41	HSPA1L, IL10, IL19, NKX2-3, TRIM22, FMNL2, RIT1, RNF5, ATXN2, SCAMP3 (+31 more)

Undrugged target profiles

49 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
STAT4	20	STAT1
HSPA1L	1	—
IL10	0	—
IL19	0	—
NKX2-3	0	—
DUOX2	1	—
TRIM22	0	—
FMNL2	0	—
RIT1	0	—
RNF5	2	—
ATXN2	5	—
SCAMP3	1	—
CXCR5	33	—
SCNN1D	0	—
CCL11	1	—
CCL13	0	—
CCL20	0	—
CCL7	2	—
CXCL5	0	—
CXCL6	0	—
ENTR1	0	—
SDF2L1	0	—
SEMA3E	0	—
SHC1	10	—
SKIC2	0	—
SLAMF1	0	—
SLC11A1	1	—
SLC22A4	29	—
SLC22A5	97	—
BRAP	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,245.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	843
PHASE2	64
PHASE1	59
PHASE4	52
PHASE3	40
PHASE1/PHASE2	17
PHASE2/PHASE3	14
EARLY_PHASE1	11

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03917303	PHASE4	RECRUITING	Control Crohn Safe Trial
NCT04646187	PHASE4	ENROLLING_BY_INVITATION	De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
NCT04835506	PHASE4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT06113913	PHASE4	RECRUITING	Subcutaneous Infliximab After A Previous Intravenous Dose Optimization
NCT06584162	PHASE4	RECRUITING	Subcutaneous Interval Lengthening of Vedolizumab for Economic Research
NCT06788340	PHASE4	NOT_YET_RECRUITING	MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
NCT06794944	PHASE4	NOT_YET_RECRUITING	Use of Fidaxomicin Compared to Vancomycin for Decolonization of C. Difficile in Patients With Inflammatory Bowel Disease
NCT07161297	PHASE4	NOT_YET_RECRUITING	Remimazolam for Colonoscopy in IBD Patients
NCT07612267	PHASE4	NOT_YET_RECRUITING	A Study to Measure Mirikizumab Levels in Breast Milk of Lactating Participants Receiving Mirikizumab Therapeutically for an Approved Indication
NCT00167882	PHASE4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00205062	PHASE4	TERMINATED	Positron Emission Tomography (PET)-Computed Tomography (CT) in Inflammatory Bowel Disease (IBD)
NCT00567593	PHASE4	COMPLETED	Gene Regulation by Thiazolidinediones
NCT00746395	PHASE4	COMPLETED	Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy
NCT01034358	PHASE4	COMPLETED	Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease
NCT01056913	PHASE4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01067547	PHASE4	COMPLETED	A Trial of Iron Replacement in Patients With Iron Deficiency.
NCT01341808	PHASE4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01908283	PHASE4	COMPLETED	Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
NCT01934088	PHASE4	COMPLETED	Satisfaction With Nurse Administered Propofol Sedation vs. Midazolam With Fentanyl Sedation for Endoscopy
NCT02162862	PHASE4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02248337	PHASE4	COMPLETED	Low Volume Colon Preparation for IBD
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02392286	PHASE4	TERMINATED	Corticosteroid Dosage for Crohn’s Disease Flare
NCT02437591	PHASE4	COMPLETED	Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
NCT02453776	PHASE4	COMPLETED	Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
NCT02461758	PHASE4	COMPLETED	Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
NCT02566889	PHASE4	TERMINATED	An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
NCT02774057	PHASE4	UNKNOWN	Trial of Captafer® vs. Oral Iron Sulfate in the Treatment of Iron Deficiency Anemia in Patients With IBD
NCT02806206	PHASE4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT02946203	PHASE4	COMPLETED	Comparison of VoLumen and Breeza Oral Contrast Agents in Pediatric Patients
NCT02994836	PHASE4	COMPLETED	GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )
NCT03220841	PHASE4	UNKNOWN	Stricture Definition and Treatment (STRIDENT) Drug Therapy Study
NCT03351972	PHASE4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03466983	PHASE4	COMPLETED	A Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia Due to Inflammatory Bowel Disease
NCT03591770	PHASE4	TERMINATED	Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
NCT03629379	PHASE4	COMPLETED	Response to Ustekinumab for Anti-tnf Induced Psoriasiform Skin Lesions
NCT03723447	PHASE4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT03798691	PHASE4	COMPLETED	Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab
NCT03860012	PHASE4	UNKNOWN	Folic Acid in Pediatric Inflammatory Bowel Disease
NCT03885713	PHASE4	COMPLETED	Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MESALAMINE	4	9
VEDOLIZUMAB	4	9
INFLIXIMAB	4	7
FERRIC CARBOXYMALTOSE	4	4
FERRIC MALTOL	4	4
PRUCALOPRIDE	4	4
ROSIGLITAZONE	4	4
ADALIMUMAB	4	3
IRON SUCROSE	4	3
ONDANSETRON	4	3
PICOSULFURIC ACID	4	3
USTEKINUMAB	4	3
AZATHIOPRINE	4	2
BALSALAZIDE DISODIUM	4	2
BEZLOTOXUMAB	4	2
DEUCRAVACITINIB	4	2
FENOFIBRATE	4	2
FERROUS FUMARATE	4	2
FERROUS SULFATE	4	2
FIDAXOMICIN	4	2
HEPATITIS B VIRUS HBSAG SURFACE PROTEIN ANTIGEN	4	2
INULIN	4	2
MIRIKIZUMAB	4	2
NEOMYCIN	4	2
PENTOXIFYLLINE	4	2
VARICELLA ZOSTER VIRUS ENVELOPE GLYCOPROTEIN E	4	2
AMITRIPTYLINE	4	1
AMITRIPTYLINE HYDROCHLORIDE	4	1
BARIUM SULFATE	4	1
CANNABIDIOL	4	1