Skeletal dysplasia

disease
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Also known as Mendelian skeletal dysplasiaprimary bone dysplasiaprimary osteodysplasiaprimary skeletal dysplasia

Summary

Skeletal dysplasia (MONDO:0018230) is a disease (an umbrella term covering 119 Mondo subtypes) caused by variants in SEMA3A, KIF5B, MGP, and 2 other genes, with 49 cohort genes and 7 clinical trials. The dominant Reactome pathway is Assembly of collagen fibrils and other multimeric structures (6 cohort genes).

At a glance

  • Causal genes: SEMA3A (GenCC Definitive), KIF5B (GenCC Strong), MGP (GenCC Strong), SLC26A2 (GenCC Strong) (+1 more)
  • Umbrella term: 119 Mondo subtypes
  • Cohort genes: 49
  • ClinVar variants: 88
  • Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameskeletal dysplasia
Mondo IDMONDO:0018230
Orphanet364526
UMLSC0410528
MedGen98053
Is cancer (heuristic)no

Also known as: Mendelian skeletal dysplasia · primary bone dysplasia · primary osteodysplasia · primary skeletal dysplasia

Data availability: 88 ClinVar variants · 11 GenCC gene-disease records.

Disease family

An umbrella term covering 119 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary diseaseskeletal dysplasia

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, inflammatory bowel 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, 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 (119): osteochondrodysplasia, diaphyseal medullary stenosis-bone malignancy syndrome, fibular aplasia-ectrodactyly syndrome, cerebrocostomandibular syndrome, cleidorhizomelic syndrome, dyschondrosteosis-nephritis syndrome, dysplasia epiphysealis hemimelica, carpotarsal osteochondromatosis, Camurati-Engelmann disease, genochondromatosis, autosomal dominant osteosclerosis, Worth type, coxopodopatellar syndrome, Lenz-Majewski hyperostotic dwarfism, delayed membranous cranial ossification, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, oculodentodigital dysplasia, Ollier disease, osteoglophonic dysplasia, parietal foramina with cleidocranial dysplasia, chondromalacia patellae, Currarino triad, Proteus syndrome, brachydactyly-elbow wrist dysplasia syndrome, tricho-dento-osseous syndrome, bird headed-dwarfism, Montreal type, Yunis-Varon syndrome, split hand-foot malformation 1 with sensorineural hearing loss, ghosal hematodiaphyseal dysplasia, hyperostosis corticalis generalisata, Larsen-like syndrome, B3GAT3 type, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal acroscyphodysplasia, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, familial osteodysplasia, Anderson type, pseudodiastrophic dysplasia, rhizomelic syndrome, Urbach type, Richieri Costa-Pereira syndrome, craniometadiaphyseal dysplasia, wormian bone type, Weaver syndrome, SHOX-related short stature, craniofrontonasal syndrome, Eiken syndrome, 2q37 microdeletion syndrome, skeletal dysplasia-epilepsy-short stature syndrome, rhizomelic dysplasia, Patterson-Lowry type, pelvic dysplasia-arthrogryposis of lower limbs syndrome, Marshall-Smith syndrome, baby rattle pelvis dysplasia, metaphyseal dysplasia, Braun-Tinschert type, genitopatellar syndrome, osteofibrous dysplasia, Larsen-like osseous dysplasia-short stature syndrome, pancreatic insufficiency-anemia-hyperostosis syndrome, microcephalic primordial dwarfism due to ZNF335 deficiency, Hartsfield-Bixler-Demyer syndrome, colobomatous microphthalmia-rhizomelic dysplasia syndrome, Tatton-Brown-Rahman overgrowth syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, Catel-Manzke syndrome, cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome, complex lethal osteochondrodysplasia, amniotic band syndrome, metaphyseal anadysplasia, syndromic craniosynostosis, thin ribs-tubular bones-dysmorphism syndrome, dysplasia of head of femur, Meyer type, epimetaphyseal skeletal dysplasia, melorheostosis with osteopoikilosis, Cole-Carpenter syndrome, spondylometaphyseal dysplasia, omodysplasia, Bruck syndrome, osteopetrosis, congenital absence of upper arm and forearm with hand present, congenital absence of thigh and lower leg with foot present, congenital absence of both forearm and hand, congenital absence of both lower leg and foot, acheiria, apodia, chondroectodermal dysplasia with night blindness, TRPV4-related bone disorder, adactyly of foot, short stature-advanced bone age-early-onset osteoarthritis syndrome, McCune-Albright syndrome, parietal foramina, Sotos syndrome, dysspondyloenchondromatosis, autosomal recessive cutis laxa type 2, FGFR3-related chondrodysplasia, filamin-related bone disorder, short rib dysplasia, spondylodysplastic dysplasia, acromelic dysplasia, bent bone dysplasia, chondrodysplasia punctata, primary osteolysis, non-syndromic limb reduction defect, Robinow syndrome, synpolydactyly, acrocoxomesomelic dysplasia, bone dysplasia Moore type, bone dysplasia corpus callosum agenesis, type 2 collagenopathy, LRP5-related primary osteoporosis, SLC26A2-related skeletal dysplasia, COMP-related skeletal dysplasia, primordial dwarfism and slender bone disorder, polydactyly-syndactyly-triphalangism, lysosomal storage disease with skeletal involvement, abnormal mineralization disorder, calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia, de la Chapelle dysplasia, mesomelic dysplasia-digital anomalies-intellectual disability syndrome, proximal femoral focal deficiency, rhizomelic dysplasia, Ain-Naz type, craniotubular dysplasia, Ikegawa type, TRIP11-related skeletal dysplasia, FAM111A-related skeletal dysplasia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

88 retrieved; paginated sample, class counts are floors:

26 pathogenic, 17 conflicting classifications of pathogenicity, 13 uncertain significance, 12 not provided, 10 pathogenic/likely pathogenic, 6 likely pathogenic, 2 benign/likely benign, 1 likely benign, 1 benign

ClinVarVariant (HGVS)GeneClassificationReview
17326NM_000088.4(COL1A1):c.1777G>A (p.Gly593Ser)COL1A1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
374196NM_000089.4(COL1A2):c.2549G>A (p.Gly850Glu)COL1A2Pathogeniccriteria provided, single submitter
1678525NM_001144061.2(COPB1):c.2102A>G (p.Gln701Arg)COPB1Pathogenicno assertion criteria provided
684727NM_000396.4(CTSK):c.905G>A (p.Trp302Ter)CTSKPathogeniccriteria provided, multiple submitters, no conflicts
635966Single alleleDIPK2BPathogeniccriteria provided, single submitter
16332NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys)FGFR3Pathogeniccriteria provided, multiple submitters, no conflicts
384194NM_000512.5(GALNS):c.611A>G (p.Asn204Ser)GALNSPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
93178NM_000512.5(GALNS):c.463G>A (p.Gly155Arg)GALNSPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
400NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys)INPP5EPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
6282NM_002335.4(LRP5):c.724G>A (p.Ala242Thr)LRP5Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
523434NM_019023.5(PRMT7):c.1713C>A (p.Cys571Ter)PRMT7Pathogeniccriteria provided, multiple submitters, no conflicts
523435NM_019023.5(PRMT7):c.322G>T (p.Glu108Ter)PRMT7Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
4682123NR_003051.4(RMRP):n.180G>ARMRPPathogenicno assertion criteria provided
633396NR_003051.3(RMRP):n.-13_1dupAAGCTGAGGACGTGRMRPPathogeniccriteria provided, multiple submitters, no conflicts
1684630NC_000017.11:g.8117792_8126946delTRG-GCC2-6Pathogeniccriteria provided, single submitter
126463NM_021625.5(TRPV4):c.1219A>G (p.Lys407Glu)TRPV4Pathogeniccriteria provided, multiple submitters, no conflicts
126464NM_021625.5(TRPV4):c.1412_1414del (p.Phe471del)TRPV4Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
126472NM_021625.5(TRPV4):c.1851C>A (p.Phe617Leu)TRPV4Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
126473NM_021625.5(TRPV4):c.1853T>C (p.Leu618Pro)TRPV4Pathogeniccriteria provided, single submitter
126478NM_021625.5(TRPV4):c.2396_2412del (p.Pro799fs)TRPV4Pathogenicno assertion criteria provided
18431NM_021625.5(TRPV4):c.2395C>T (p.Pro799Ser)TRPV4Pathogenicno assertion criteria provided
18434NM_021625.5(TRPV4):c.832G>A (p.Glu278Lys)TRPV4Pathogeniccriteria provided, single submitter
18435NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys)TRPV4Pathogeniccriteria provided, multiple submitters, no conflicts
30468NM_021625.5(TRPV4):c.1805A>G (p.Tyr602Cys)TRPV4Pathogenicno assertion criteria provided
30469NM_021625.5(TRPV4):c.1625C>A (p.Ser542Tyr)TRPV4Pathogeniccriteria provided, single submitter
30470NM_021625.5(TRPV4):c.266C>T (p.Thr89Ile)TRPV4Pathogeniccriteria provided, single submitter
30472NM_021625.5(TRPV4):c.694C>T (p.Arg232Cys)TRPV4Pathogeniccriteria provided, multiple submitters, no conflicts
30474NM_021625.5(TRPV4):c.232G>T (p.Gly78Trp)TRPV4Pathogenicno assertion criteria provided
30475NM_021625.5(TRPV4):c.2219C>T (p.Thr740Ile)TRPV4Pathogenicno assertion criteria provided
30476NM_021625.5(TRPV4):c.826A>G (p.Lys276Glu)TRPV4Pathogeniccriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 47 · Orphanet: 181 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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.

GeneClassificationInheritanceDiseaseRecords
ANKHDefinitiveAutosomal dominantcraniometaphyseal dysplasia, autosomal dominant11
SEMA3ADefinitiveAutosomal recessiveskeletal dysplasia7
SLC26A2DefinitiveAutosomal recessiveSLC26A2-related skeletal dysplasia13
KIF5BStrongAutosomal dominantskeletal dysplasia2
MGPStrongAutosomal dominantskeletal dysplasia6
TMEM53StrongAutosomal recessivecraniotubular dysplasia, Ikegawa type2
BMP5LimitedAutosomal recessiveskeletal dysplasia2
LOXL4LimitedAutosomal dominantskeletal dysplasia
MSGN1LimitedAutosomal recessiveskeletal dysplasia
SEMA3DLimitedAutosomal dominantskeletal dysplasia
UXS1LimitedAutosomal dominantskeletal dysplasia

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SEMA3AOrphanet:130Brugada syndrome
SEMA3AOrphanet:478Kallmann syndrome
SEMA3DOrphanet:388Hirschsprung disease
SLC26A2Orphanet:56304Atelosteogenesis type II
SLC26A2Orphanet:628Diastrophic dysplasia
SLC26A2Orphanet:93298Achondrogenesis type 1B
SLC26A2Orphanet:93307Multiple epiphyseal dysplasia type 4
ANKHOrphanet:1416Familial calcium pyrophosphate deposition
ANKHOrphanet:1522Craniometaphyseal dysplasia
MGPOrphanet:85202Keutel syndrome
RMRPOrphanet:175Cartilage-hair hypoplasia
RMRPOrphanet:39041Omenn syndrome
RMRPOrphanet:93347Anauxetic dysplasia
ARID1AOrphanet:1465Coffin-Siris syndrome
TTNOrphanet:140922Titin-related limb-girdle muscular dystrophy R10
TTNOrphanet:154Familial isolated dilated cardiomyopathy
TTNOrphanet:169186Autosomal recessive centronuclear myopathy
TTNOrphanet:178464Hereditary myopathy with early respiratory failure
TTNOrphanet:289377Early-onset myopathy with fatal cardiomyopathy
TTNOrphanet:293888Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTNOrphanet:293899Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTNOrphanet:293910Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTNOrphanet:324604Classic multiminicore myopathy
TTNOrphanet:334Hereditary atrial fibrillation
TTNOrphanet:466921Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTNOrphanet:609Tibial muscular dystrophy
TTNOrphanet:707983Early-onset autosomal recessive TTN-related distal myopathy
LMBR1Orphanet:2378Laurin-Sandrow syndrome
LMBR1Orphanet:931Isolated acheiropodia
LMBR1Orphanet:93321Isolated radial hemimelia
LMBR1Orphanet:93336Polydactyly of a triphalangeal thumb
LMBR1Orphanet:93405Syndactyly type 4
LMBR1Orphanet:988Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome
MACF1Orphanet:572013Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects syndrome
CACNA1DOrphanet:324321Sinoatrial node dysfunction and deafness
CACNA1DOrphanet:369929Primary hyperaldosteronism-seizures-neurological abnormalities syndrome
MBTPS2Orphanet:216796Osteogenesis imperfecta type 1
MBTPS2Orphanet:216812Osteogenesis imperfecta type 3
MBTPS2Orphanet:216820Osteogenesis imperfecta type 4
MBTPS2Orphanet:2273Ichthyosis follicularis-alopecia-photophobia syndrome
MBTPS2Orphanet:2340Keratosis follicularis spinulosa decalvans
MBTPS2Orphanet:659Mutilating palmoplantar keratoderma with periorificial keratotic plaques
MBTPS2Orphanet:85284BRESEK syndrome
TP63Orphanet:1072Ankyloblepharon filiforme adnatum-cleft palate syndrome
TP63Orphanet:141291Cleft lip and alveolus
TP63Orphanet:1896EEC syndrome
TP63Orphanet:199302Isolated cleft lip
TP63Orphanet:199306Cleft lip/palate
TP63Orphanet:2440Isolated split hand-split foot malformation
TP63Orphanet:69085Limb-mammary syndrome

Cohort genes → proteins

49 cohort genes, 46 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence49

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
KIF5BHGNC:6324ENSG00000170759P33176Kinesin-1 heavy chaingencc,clinvar
BMP5HGNC:1072ENSG00000112175P22003Bone morphogenetic protein 5gencc
SEMA3AHGNC:10723ENSG00000075213Q14563Semaphorin-3Agencc
SEMA3DHGNC:10726ENSG00000153993O95025Semaphorin-3Dgencc
SLC26A2HGNC:10994ENSG00000155850P50443Sulfate transportergencc
MSGN1HGNC:14907ENSG00000151379A6NI15Mesogenin-1gencc
ANKHHGNC:15492ENSG00000154122Q9HCJ1Mineralization regulator ANKHgencc
LOXL4HGNC:17171ENSG00000138131Q96JB6Lysyl oxidase homolog 4gencc
UXS1HGNC:17729ENSG00000115652Q8NBZ7UDP-glucuronic acid decarboxylase 1gencc
TMEM53HGNC:26186ENSG00000126106Q6P2H8Transmembrane protein 53gencc
MGPHGNC:7060ENSG00000111341P08493Matrix Gla proteingencc
RMRPHGNC:10031ENSG00000277027RNA component of mitochondrial RNA processing endoribonucleaseclinvar
ARID1AHGNC:11110ENSG00000117713O14497AT-rich interactive domain-containing protein 1Aclinvar
TRG-GCC2-6HGNC:12273tRNA-Gly (anticodon GCC) 2-6clinvar
TTNHGNC:12403ENSG00000155657Q8WZ42Titinclinvar
LMBR1HGNC:13243ENSG00000105983Q8WVP7Limb region 1 protein homologclinvar
MACF1HGNC:13664ENSG00000127603O94854Microtubule-actin cross-linking factor 1, isoforms 6/7clinvar
CACNA1DHGNC:1391ENSG00000157388Q01668Voltage-dependent L-type calcium channel subunit alpha-1Dclinvar
MBTPS2HGNC:15455ENSG00000012174O43462Membrane-bound transcription factor site-2 proteaseclinvar
TP63HGNC:15979ENSG00000073282Q9H3D4Tumor protein 63clinvar
COPS7BHGNC:16760ENSG00000144524Q9H9Q2COP9 signalosome complex subunit 7bclinvar
SYNE1HGNC:17089ENSG00000131018Q8NF91Nesprin-1clinvar
TRPV4HGNC:18083ENSG00000111199Q9HBA0Transient receptor potential cation channel subfamily V member 4clinvar
PMPCAHGNC:18667ENSG00000165688Q10713Mitochondrial-processing peptidase subunit alphaclinvar
INPP5EHGNC:21474ENSG00000148384Q9NRR6Phosphatidylinositol polyphosphate 5-phosphatase type IVclinvar
COL11A1HGNC:2186ENSG00000060718P12107Collagen alpha-1(XI) chainclinvar
COL1A1HGNC:2197ENSG00000108821P02452Collagen alpha-1(I) chainclinvar
COL1A2HGNC:2198ENSG00000164692P08123Collagen alpha-2(I) chainclinvar
COL2A1HGNC:2200ENSG00000139219P02458Collagen alpha-1(II) chainclinvar
COL9A3HGNC:2219ENSG00000092758Q14050Collagen alpha-3(IX) chainclinvar
COPB1HGNC:2231ENSG00000129083P53618Coatomer subunit betaclinvar
FAM111AHGNC:24725ENSG00000166801Q96PZ2Serine protease FAM111Aclinvar
PKDCCHGNC:25123ENSG00000162878Q504Y2Extracellular tyrosine-protein kinase PKDCCclinvar
CTSKHGNC:2536ENSG00000143387P43235Cathepsin Kclinvar
PRMT7HGNC:25557ENSG00000132600Q9NVM4Protein arginine N-methyltransferase 7clinvar
DIPK2BHGNC:25866ENSG00000147113Q9H7Y0Divergent protein kinase domain 2Bclinvar
DYNC2H1HGNC:2962ENSG00000187240Q8NCM8Cytoplasmic dynein 2 heavy chain 1clinvar
ACANHGNC:319ENSG00000157766P16112Aggrecan core proteinclinvar
FGFR3HGNC:3690ENSG00000068078P22607Fibroblast growth factor receptor 3clinvar
FLNBHGNC:3755ENSG00000136068O75369Filamin-Bclinvar
LARGE-AS1HGNC:40336ENSG00000224973LARGE antisense RNA 1clinvar
GALNSHGNC:4122ENSG00000141012P34059N-acetylgalactosamine-6-sulfataseclinvar
GNASHGNC:4392ENSG00000087460O95467Neuroendocrine secretory protein 55clinvar
ALX4HGNC:450ENSG00000052850Q9H161Homeobox protein aristaless-like 4clinvar
HOXD13HGNC:5136ENSG00000128714P35453Homeobox protein Hox-D13clinvar
KIF22HGNC:6391ENSG00000079616Q14807Kinesin-like protein KIF22clinvar
LRP5HGNC:6697ENSG00000162337O75197Low-density lipoprotein receptor-related protein 5clinvar
PAPSS2HGNC:8604ENSG00000198682O95340Bifunctional 3’-phosphoadenosine 5’-phosphosulfate synthase 2clinvar
PTH1RHGNC:9608ENSG00000160801Q03431Parathyroid hormone/parathyroid hormone-related peptide receptorclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
KIF5BKinesin-1 heavy chainMicrotubule-dependent motor required for normal distribution of mitochondria and lysosomes.
BMP5Bone morphogenetic protein 5Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cartilage and bone formation or neurogenesis.
SEMA3ASemaphorin-3AInvolved in the development of the olfactory system and in neuronal control of puberty.
SEMA3DSemaphorin-3DInduces the collapse and paralysis of neuronal growth cones.
SLC26A2Sulfate transporterSulfate transporter which mediates sulfate uptake into chondrocytes in order to maintain adequate sulfation of proteoglycans which is needed for cartilage development.
MSGN1Mesogenin-1Involved in specifying the paraxial, but not dorsal, mesoderm.
ANKHMineralization regulator ANKHTransports adenosine triphosphate (ATP) and possibly other nucleoside triphosphates (NTPs) from cytosol to the extracellular space.
LOXL4Lysyl oxidase homolog 4Catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin, resulting in the formation of covalent cross-linkages, and the stabilization of collagen and elastin fibers.
UXS1UDP-glucuronic acid decarboxylase 1Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose.
TMEM53Transmembrane protein 53Ensures normal bone formation, through the negative regulation of bone morphogenetic protein (BMP) signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of phosphorylated SMAD1/5/9 proteins.
MGPMatrix Gla proteinAssociates with the organic matrix of bone and cartilage.
ARID1AAT-rich interactive domain-containing protein 1AInvolved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
TTNTitinKey component in the assembly and functioning of vertebrate striated muscles.
LMBR1Limb region 1 protein homologPutative membrane receptor.
CACNA1DVoltage-dependent L-type calcium channel subunit alpha-1DVoltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
MBTPS2Membrane-bound transcription factor site-2 proteaseZinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2.
TP63Tumor protein 63Acts as a sequence specific DNA binding transcriptional activator or repressor.
COPS7BCOP9 signalosome complex subunit 7bComponent of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.
SYNE1Nesprin-1Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.
TRPV4Transient receptor potential cation channel subfamily V member 4Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity.
PMPCAMitochondrial-processing peptidase subunit alphaSubstrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins.
INPP5EPhosphatidylinositol polyphosphate 5-phosphatase type IVPhosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,5-bispho…
COL11A1Collagen alpha-1(XI) chainMay play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
COL1A1Collagen alpha-1(I) chainType I collagen is a member of group I collagen (fibrillar forming collagen).
COL1A2Collagen alpha-2(I) chainType I collagen is a member of group I collagen (fibrillar forming collagen).
COL2A1Collagen alpha-1(II) chainType II collagen is specific for cartilaginous tissues.
COL9A3Collagen alpha-3(IX) chainStructural component of hyaline cartilage and vitreous of the eye.
COPB1Coatomer subunit betaThe coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Go…
FAM111ASerine protease FAM111ASingle-stranded DNA-binding serine protease that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity.
PKDCCExtracellular tyrosine-protein kinase PKDCCSecreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages.
CTSKCathepsin KThiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling.
PRMT7Protein arginine N-methyltransferase 7Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA.
DYNC2H1Cytoplasmic dynein 2 heavy chain 1May function as a motor for intraflagellar retrograde transport.
ACANAggrecan core proteinThis proteoglycan is a major component of extracellular matrix of cartilagenous tissues.
FGFR3Fibroblast growth factor receptor 3Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
FLNBFilamin-BConnects cell membrane constituents to the actin cytoskeleton.
ALX4Homeobox protein aristaless-like 4Transcription factor involved in skull and limb development.
HOXD13Homeobox protein Hox-D13Sequence-specific transcription factor that binds gene promoters and activates their transcription.
KIF22Kinesin-like protein KIF22Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis.
LRP5Low-density lipoprotein receptor-related protein 5Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins.
PAPSS2Bifunctional 3’-phosphoadenosine 5’-phosphosulfate synthase 2Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway.
PTH1RParathyroid hormone/parathyroid hormone-related peptide receptorG-protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-related peptide (PTHLH).

Protein-family classification

Druggable: 21 · Difficult: 5 · Unknown: 23 · Druggable fraction: 0.43

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.

FamilyGenesFoldFDR
Protease43.0×0.266
Kinase52.8×0.266
Ion channel24.5×0.286
Complement15.5×0.503
Antibody/Immunoglobulin31.8×0.565
Phosphatase11.7×0.806
Transporter11.6×0.806
Other/Unknown230.8×0.946
Enzyme (other)30.7×0.946
Transcription factor40.7×0.946
GPCR10.5×0.946
Scaffold/PPI10.3×0.946

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
KIF5BEnzyme (other)yes5.6.1.3Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
BMP5Other/UnknownnoTGF-b_propeptide, TGF-b_C, TGF-beta-like
SEMA3AAntibody/ImmunoglobulinyesSemap_dom, Ig_sub, Ig-like_dom
SEMA3DAntibody/ImmunoglobulinyesSemap_dom, Ig_sub, Ig-like_dom
SLC26A2TransporteryesSLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom
MSGN1Transcription factornobHLH_dom, HLH_DNA-bd_sf, Mesogenin/MesP
ANKHOther/UnknownnoANKH
LOXL4Other/UnknownnoSRCR, Lysyl_oxidase, Lysyl_oxidase_CS
UXS1Other/UnknownnoNAD(P)-bd_dom, UXS1_N, NAD(P)-bd_dom_sf
TMEM53Other/UnknownnoDUF829_TMEM53, AB_hydrolase_fold
MGPOther/UnknownnoGLA_domain, Osteocalcin/MGP, MGP
RMRPOther/Unknownno
ARID1AOther/UnknownnoARID_dom, ARM-like, ARM-type_fold
TRG-GCC2-6Other/Unknownno
TTNKinaseyes2.7.11.1Prot_kinase_dom, Ig_sub2, Ig_sub
LMBR1Other/UnknownnoLMBR1-like_membr_prot, LIMR
MACF1Scaffold/PPInoSpectrin_repeat, EF_hand_dom, GAR_dom
CACNA1DIon channelyesVDCCAlpha1, VDCC_L_a1su, LVDCC_a1dsu
MBTPS2Proteaseyes3.4.24.85MBTPS2, Peptidase_M50, PDZ_sf
TP63Transcription factornoSAM, p53_tumour_suppressor, p53-like_TF_DNA-bd_sf
COPS7BOther/UnknownnoPCI_dom, CSN7_helixI, COPS7/eIF3m
SYNE1Other/UnknownnoActinin_actin-bd_CS, CH_dom, Spectrin_repeat
TRPV4Ion channelyesAnkyrin_rpt, Ion_trans_dom, TrpV1-4
PMPCAProteaseyes3.4.24.64Pept_M16_Zn_BS, Peptidase_M16_C, Metalloenz_LuxS/M16
INPP5EEnzyme (other)yes3.1.3.36IPPc, Endo/exonu/phosph_ase_sf, INPP5E
COL11A1Other/UnknownnoFib_collagen_C, Laminin_G, Collagen
COL1A1Other/UnknownnoFib_collagen_C, VWF_dom, Collagen
COL1A2Other/UnknownnoFib_collagen_C, Collagen, Collagen_superfamily
COL2A1Other/UnknownnoFib_collagen_C, VWF_dom, Collagen
COL9A3Other/UnknownnoCollagen, Collagen_superfamily
COPB1Other/UnknownnoClathrin/coatomer_adapt-like_N, Coatomer_bsu_C, ARM-like
FAM111AProteaseyesPeptidase_S1_PA,
PKDCCKinaseyesProt_kinase_dom, Kinase-like_dom_sf, FAM69_kinase_dom
CTSKProteaseyes3.4.22.38Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A
PRMT7Enzyme (other)yes2.1.1.321MeTrfase_PRMT7, Arg_MeTrfase, SAM-dependent_MTases_sf
DIPK2BKinaseyesDIPK2A/B, FAM69_kinase_dom
DYNC2H1Other/UnknownnoAAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
ACANComplementyesSushi_SCR_CCP_dom, Link_dom, EGF
FGFR3Kinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FLNBAntibody/ImmunoglobulinyesFilamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
LARGE-AS1Other/Unknownno
GALNSPhosphataseyes3.1.6.12Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS
GNASOther/UnknownnoNESP55, Gprotein_alpha_S, Gprotein_alpha_su
ALX4Transcription factornoHD, OAR_dom, Homeodomain-like_sf
HOXD13Transcription factornoHD, Homeodomain-like_sf, Homeobox_CS
KIF22Other/UnknownnoKinesin_motor_dom, Hlx-hairpin-Hlx_DNA-bd_motif, RuvA_2-like
LRP5Other/UnknownnoLDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
PAPSS2Kinaseyes2.7.1.25Sulphate_adenylyltransferase, APS, Rossmann-like_a/b/a_fold
PTH1RGPCRyesGPCR_2_secretin-like, GPCR_2_extracellular_dom, GPCR_2_parathyroid_rcpt

Expression context

Cohort genes with no expression data: 1.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)1
broad (>20)47
unknown1

Top tissues across cohort

TissueCohort genes
tibia9
cartilage tissue7
skin of hip5
stromal cell of endometrium4
mucosa of transverse colon4
adrenal tissue4
right uterine tube4
periodontal ligament4
calcaneal tendon3
colonic epithelium3
buccal mucosa cell3
bone marrow cell3
secondary oocyte3
right lobe of liver3
sperm3
cranial nerve II2
islet of Langerhans2
mucosa of sigmoid colon2
olfactory segment of nasal mucosa2
inferior vagus X ganglion2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
KIF5B303ubiquitousmarkercauda epididymis, caput epididymis, cranial nerve II
BMP5153broadmarkercalcaneal tendon, islet of Langerhans, cartilage tissue
SEMA3A194ubiquitousmarkerstromal cell of endometrium, cortical plate, colonic epithelium
SEMA3D183ubiquitousmarkerbuccal mucosa cell, tendon of biceps brachii, spleen
SLC26A2282ubiquitousmarkercolonic mucosa, mucosa of sigmoid colon, mucosa of transverse colon
MSGN116tissue_specificmarkerbone marrow cell, colonic epithelium, olfactory segment of nasal mucosa
ANKH273ubiquitousmarkertibia, parotid gland, inferior vagus X ganglion
LOXL4194broadmarkertibia, islet of Langerhans, cartilage tissue
UXS1286ubiquitousmarkersecondary oocyte, renal medulla, oocyte
TMEM53207ubiquitousmarkerright lobe of liver, mucosa of transverse colon, sperm
MGP274ubiquitousmarkerascending aorta, thoracic aorta, descending thoracic aorta
RMRP128ubiquitousyescorpus callosum, colonic epithelium, bone marrow cell
ARID1A286ubiquitousmarkerbone marrow cell, ventricular zone, embryo
TRG-GCC2-6
TTN223broadmarkerbiceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
LMBR1249ubiquitousmarkeradrenal tissue, sural nerve, calcaneal tendon
MACF1303ubiquitousmarkerinferior olivary complex, dorsal motor nucleus of vagus nerve, right lung
CACNA1D219broadmarkerbuccal mucosa cell, adrenal tissue, right lung
MBTPS2264ubiquitousmarkerendothelial cell, tibia, parietal pleura
TP63207broadmarkerupper leg skin, skin of hip, upper arm skin
COPS7B243ubiquitousmarkerright uterine tube, right testis, left testis
SYNE1275ubiquitousmarkercerebellar hemisphere, right hemisphere of cerebellum, calcaneal tendon
TRPV4171ubiquitousmarkercartilage tissue, lower esophagus mucosa, olfactory segment of nasal mucosa
PMPCA276ubiquitousmarkerright lobe of liver, adrenal tissue, apex of heart
INPP5E279ubiquitousyesright uterine tube, secondary oocyte, oocyte
COL11A1209broadmarkertibia, cartilage tissue, periodontal ligament
COL1A1298ubiquitousmarkerstromal cell of endometrium, skin of hip, periodontal ligament
COL1A2295ubiquitousmarkerperiodontal ligament, stromal cell of endometrium, skin of hip
COL2A1145broadmarkertibia, cartilage tissue, corpus epididymis
COL9A3218broadmarkertibia, cartilage tissue, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 18.

Hub genes (top 10 by interactor count)

SymbolInteractor count
COL1A15,341
FGFR34,510
TTN4,237
PMPCA3,679
KIF5B3,606
ARID1A3,476
UXS13,320
COPB13,098
FLNB2,927
TP632,893

Intra-cohort edges

ABSources
ANKHMGPstring_interaction
COL11A1COL1A1string_interaction
COL11A1COL2A1string_interaction
COL11A1COL9A3string_interaction
COL1A1COL1A2intact
COL1A1COL2A1intact
COL2A1COL9A3string_interaction
COL2A1FGFR3intact, string_interaction
COL2A1SLC26A2string_interaction
COL9A3SLC26A2string_interaction
CTSKFGFR3intact
DIPK2BPKDCCstring_interaction
FGFR3LOXL4intact
HOXD13LMBR1string_interaction
LMBR1UXS1biogrid_interaction
LRP5PTH1Rstring_interaction
PAPSS2SLC26A2string_interaction
SYNE1TTNstring_interaction

Structural data

PDB: 29 · AlphaFold-only: 17 · No structure: 3

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
GNASO95467490
CTSKP4323570
TTNQ8WZ4264
PTH1RQ0343148
KIF5BP3317631
TP63Q9H3D426
COPS7BQ9H9Q225
FLNBO7536923
TRPV4Q9HBA019
FGFR3P2260715
COL1A1P0245214
COL2A1P0245811
ARID1AO144977
CACNA1DQ016686
COL1A2P081235
PAPSS2O953405
SLC26A2P504434
UXS1Q8NBZ74
COL9A3Q140504
DYNC2H1Q8NCM84
ACANP161124
ALX4Q9H1614
MGPP084933
MACF1O948543
SYNE1Q8NF913
FAM111AQ96PZ22
GALNSP340592
KIF22Q148072
INPP5EQ9NRR61

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PRMT7Q9NVM493.19
TMEM53Q6P2H889.97
PMPCAQ1071388.46
MBTPS2O4346287.78
LOXL4Q96JB686.43
ANKHQ9HCJ184.57
SEMA3AQ1456384.50
DIPK2BQ9H7Y084.17
SEMA3DO9502584.10
PKDCCQ504Y282.96
COPB1P5361882.55
LMBR1Q8WVP779.49
LRP5O7519778.65
BMP5P2200374.85
MSGN1A6NI1568.43
HOXD13P3545357.18
COL11A1P1210753.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 214. Enrichment computed across 49 evidence-associated genes (35 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 35 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Assembly of collagen fibrils and other multimeric structures634.4×4e-06LOXL4, COL11A1, COL1A1, COL1A2, COL2A1, COL9A3
Collagen degradation630.1×4e-06COL11A1, COL1A1, COL1A2, COL2A1, COL9A3, CTSK
Collagen chain trimerization537.1×1e-05COL11A1, COL1A1, COL1A2, COL2A1, COL9A3
MET activates PTK2 signaling443.5×8e-05COL11A1, COL1A1, COL1A2, COL2A1
Collagen biosynthesis and modifying enzymes524.4×8e-05COL11A1, COL1A1, COL1A2, COL2A1, COL9A3
ECM proteoglycans521.5×1e-04COL1A1, COL1A2, COL2A1, COL9A3, ACAN
Developmental Lineage of Pancreatic Ductal Cells426.1×5e-04COL11A1, COL1A1, COL1A2, COL2A1
Defective VWF binding to collagen type I2217.5×6e-04COL1A1, COL1A2
Fibronectin matrix formation348.9×6e-04COL1A1, COL1A2, COL2A1
Crosslinking of collagen fibrils348.9×6e-04LOXL4, COL1A1, COL1A2
Enhanced cleavage of VWF variant by ADAMTS132163.1×1e-03COL1A1, COL1A2
Defective VWF cleavage by ADAMTS13 variant2163.1×1e-03COL1A1, COL1A2
Non-integrin membrane-ECM interactions417.6×0.001COL11A1, COL1A1, COL1A2, COL2A1
Integrin cell surface interactions415.3×0.002COL1A1, COL1A2, COL2A1, COL9A3
Transport and metabolism of PAPS293.2×0.002SLC26A2, PAPSS2
Enhanced binding of GP1BA variant to VWF multimer:collagen293.2×0.002COL1A1, COL1A2
Defective binding of VWF variant to GPIb:IX:V293.2×0.002COL1A1, COL1A2
NCAM1 interactions321.3×0.004CACNA1D, COL2A1, COL9A3
GP1b-IX-V activation signalling254.4×0.007COL1A1, COL1A2
Anchoring fibril formation243.5×0.010COL1A1, COL1A2
Keratan sulfate degradation240.8×0.011ACAN, GALNS
Platelet Adhesion to exposed collagen238.4×0.012COL1A1, COL1A2
Scavenging by Class A Receptors234.4×0.014COL1A1, COL1A2
t(4;14) translocations of FGFR31326.3×0.022FGFR3
MPS IV - Morquio syndrome A1326.3×0.022GALNS
Defective SLC26A2 causes chondrodysplasias1326.3×0.022SLC26A2
Defective PAPSS2 causes SEMD-PA1326.3×0.022PAPSS2
Signaling by FGFR3 fusions in cancer1326.3×0.022FGFR3
Platelet Aggregation (Plug Formation)225.1×0.022COL1A1, COL1A2
Syndecan interactions224.2×0.022COL1A1, COL1A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 44 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
skeletal system development1234.3×3e-13BMP5, ANKH, TP63, COL1A1, COL1A2, COL2A1, PKDCC, ACAN (+4 more)
cartilage development involved in endochondral bone morphogenesis3164.1×9e-05TRPV4, COL1A1, COL2A1
bone mineralization530.9×9e-05ANKH, COL1A2, PKDCC, FGFR3, PTH1R
collagen fibril organization525.5×2e-04LOXL4, COL11A1, COL1A1, COL1A2, COL2A1
skin morphogenesis395.8×4e-04TP63, COL1A1, COL1A2
chondrocyte differentiation427.4×9e-04SLC26A2, COL2A1, FGFR3, PTH1R
embryonic digit morphogenesis427.4×9e-04LMBR1, ALX4, HOXD13, LRP5
bone maturation2255.3×0.001MBTPS2, FGFR3
cartilage condensation352.2×0.001COL11A1, COL2A1, MGP
endochondral ossification337.1×0.003COL1A1, COL2A1, FGFR3
anterior head development2127.7×0.004BMP5, COL2A1
proteoglycan metabolic process285.1×0.010COL11A1, COL2A1
chondrocyte proliferation247.9×0.027SLC26A2, FGFR3
roof of mouth development316.9×0.027COL2A1, PKDCC, ALX4
osteoblast development245.1×0.029LRP5, PTH1R
sensory perception of sound49.2×0.029CACNA1D, COL11A1, COL1A1, COL2A1
sympathetic nervous system development242.6×0.029SEMA3A, TP63
male genitalia development240.3×0.030BMP5, HOXD13
calcium ion import236.5×0.035CACNA1D, TRPV4
ectoderm and mesoderm interaction1383.0×0.038TP63
epidermal cell division1383.0×0.038TP63
UDP-D-xylose biosynthetic process1383.0×0.038UXS1
hyperosmotic salinity response1383.0×0.038TRPV4
negative regulation of developmental growth1383.0×0.038FGFR3
branch elongation of an epithelium1383.0×0.038HOXD13
protein heterotrimerization1383.0×0.038COL1A2
cellular response to vitamin E1383.0×0.038COL1A1
blood vessel endothelial cell delamination1383.0×0.038TRPV4
regulation of bone mineralization233.3×0.038ANKH, MGP
negative chemotaxis229.5×0.038SEMA3A, SEMA3D

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 8 · Phased (≥1): 9 · Undrugged: 40

Druggability breadth: 24 of 49 evidence-associated genes (49%) 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.

SymbolExample approved molecule
KIF5BLENVATINIB
LOXL4PYRITHIONE
CACNA1DBEPRIDIL
CTSKBOCEPREVIR
FGFR3PONATINIB
PTH1RABALOPARATIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
FGFR3644
CACNA1D484
CTSK84
TRPV463
KIF5B34
LOXL434
PTH1R34
COPB112
PRMT713
BMP500

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
LENVATINIB4FGFR3, KIF5B
CABOZANTINIB4KIF5B
VANDETANIB4FGFR3, KIF5B
PYRITHIONE4LOXL4
DISULFIRAM4LOXL4
BEPRIDIL4CACNA1D
IMIPRAMINE4CACNA1D
HALOFANTRINE4CACNA1D
DROPERIDOL4CACNA1D
SAQUINAVIR4CACNA1D
DULOXETINE4CACNA1D
DIAZEPAM4CACNA1D
SERTINDOLE4CACNA1D
QUINIDINE4CACNA1D
LAMIVUDINE4CACNA1D
PIMOZIDE4CACNA1D
PHENYTOIN4CACNA1D
TERFENADINE4CACNA1D
CISAPRIDE4CACNA1D
SOLIFENACIN4CACNA1D
NIFEDIPINE4CACNA1D
DILTIAZEM4CACNA1D
NILOTINIB4CACNA1D
ASTEMIZOLE4CACNA1D
TERODILINE4CACNA1D
CLOZAPINE4CACNA1D
MIBEFRADIL4CACNA1D
DOFETILIDE4CACNA1D
THIORIDAZINE4CACNA1D
PAROXETINE4CACNA1D

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

SymbolAssaysType breakdown
FGFR3975Binding:948, Functional:18, ADMET:9
CTSK376Binding:365, ADMET:5, Toxicity:5, Functional:1
CACNA1D233Binding:145, Functional:81, Toxicity:5, ADMET:2
PRMT7100Binding:98, Functional:2
TRPV499Binding:94, Functional:5
PTH1R59Functional:42, Binding:17
KIF5B43Binding:37, Functional:6
GALNS15Binding:15
COPB19Binding:9
COL1A18Binding:8
ARID1A6Binding:6
COL1A24Functional:4
KIF224Binding:4
LOXL43Binding:3
COL2A12Binding:2
FLNB2Binding:2
PAPSS22Binding:2
TTN1Binding:1
COPS7B1Binding:1
PMPCA1Binding:1
LRP51Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
KIF5B5.6.1.3plus-end-directed kinesin ATPase
TTN2.7.11.1non-specific serine/threonine protein kinase
MBTPS23.4.24.85S2P endopeptidase
PMPCA3.4.24.64mitochondrial processing peptidase
INPP5E3.1.3.36phosphoinositide 5-phosphatase
CTSK3.4.22.38cathepsin K
PRMT72.1.1.321type III protein arginine methyltransferase
FGFR32.7.10.1receptor protein-tyrosine kinase
GALNS3.1.6.12, 3.1.6.4N-acetylgalactosamine-4-sulfatase, N-acetylgalactosamine-6-sulfatase
PAPSS22.7.1.25, 2.7.7.4adenylyl-sulfate kinase, sulfate adenylyltransferase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CACNA1D233
CTSK376
PRMT7100
FGFR3975

Pharmacogenomics

Cohort genes with a PharmGKB record: 47; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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.

CompoundMax phaseCohort target (bioactivity)
LENVATINIB4FGFR3, KIF5B
CABOZANTINIB4KIF5B
VANDETANIB4FGFR3, KIF5B
PYRITHIONE4LOXL4
DISULFIRAM4LOXL4
BEPRIDIL4CACNA1D
IMIPRAMINE4CACNA1D
HALOFANTRINE4CACNA1D
DROPERIDOL4CACNA1D
SAQUINAVIR4CACNA1D
DULOXETINE4CACNA1D
DIAZEPAM4CACNA1D
SERTINDOLE4CACNA1D
QUINIDINE4CACNA1D
LAMIVUDINE4CACNA1D
PIMOZIDE4CACNA1D
PHENYTOIN4CACNA1D
TERFENADINE4CACNA1D
CISAPRIDE4CACNA1D
SOLIFENACIN4CACNA1D
NIFEDIPINE4CACNA1D
DILTIAZEM4CACNA1D
NILOTINIB4CACNA1D
ASTEMIZOLE4CACNA1D
TERODILINE4CACNA1D
CLOZAPINE4CACNA1D
MIBEFRADIL4CACNA1D
DOFETILIDE4CACNA1D
THIORIDAZINE4CACNA1D
PAROXETINE4CACNA1D

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)6KIF5B, LOXL4, CACNA1D, CTSK, FGFR3, PTH1R
BPhased (≥1) drug, not yet approved3TRPV4, COPB1, PRMT7
CDruggable family + PDB, no drug8SLC26A2, TTN, INPP5E, FAM111A, ACAN, FLNB, GALNS, PAPSS2
DDruggable family + AlphaFold only, no drug6SEMA3A, SEMA3D, MBTPS2, PMPCA, PKDCC, DIPK2B
EDifficult family or no structure, no drug26BMP5, MSGN1, ANKH, UXS1, TMEM53, MGP, RMRP, ARID1A, TRG-GCC2-6, LMBR1 (+16 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
BMP50
SEMA3A0
SEMA3D0
SLC26A20
MSGN10
ANKH0
UXS10
TMEM530
MGP0
RMRP0
ARID1A6
TRG-GCC2-60
TTN1
LMBR10
MACF10
MBTPS20
TP630
COPS7B1
SYNE10
PMPCA1
INPP5E0
COL11A10
COL1A18
COL1A24
COL2A12
COL9A30
FAM111A0
PKDCC0
DIPK2B0
DYNC2H10

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified7

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05247645Not specifiedRECRUITINGData Collection of Patients With Rare Bone Diseases
NCT05876416Not specifiedRECRUITINGDecoding the Genetic Landscape of Skeletal Diseases
NCT05991609Not specifiedACTIVE_NOT_RECRUITINGExtreme Morphology and Metabolic Health
NCT00001754Not specifiedCOMPLETEDStudy of Skeletal Disorders and Short Stature
NCT02762318Not specifiedTERMINATEDIdentification and Characterization of Bone-related Genetic Variants in Families
NCT03548779Not specifiedCOMPLETEDNorth Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT06002373Not specifiedUNKNOWNAssessment of Artificial Intelligence for Treatment Decision Recommendation of Adult Skeletal Class III Patients