Hypospadias

Summary

Hypospadias (MONDO:0005345) is a disease (an umbrella term covering 5 Mondo subtypes) with 35 cohort genes (26 GWAS associations across 4 studies) and 88 clinical trials. The dominant Reactome pathway is Formation of the ureteric bud (3 cohort genes). Top therapeutic interventions include neostigmine, ropivacaine, and atropine.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 35
• GWAS associations: 26
• ClinVar variants: 9
• Clinical trials: 88

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypospadias
Mondo ID	MONDO:0005345
EFO	EFO:0004209
MeSH	D007021
OMIM	300633
Orphanet	440
DOID	DOID:10892
ICD-10-CM	Q54
ICD-11	810247271
NCIT	C40341
SNOMED CT	416010008
UMLS	C0848558
MedGen	163083
Is cancer (heuristic)	no

Also known as: hypospadias · hypospadias (disease) · hypospadias familial

Data availability: 9 ClinVar variants · 26 GWAS associations (4 studies) · 2 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

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

Subtypes (5): hypospadias 3, autosomal, hypospadias 1, X-linked, hypospadias 2, X-linked, hypospadias 4, X-linked, isolated female hypospadias

Genetics & variants

GWAS landscape

26 GWAS associations across 4 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs4554617	1e-93	DGKK	C	2.52
rs3816183	4e-34	HAAO	T	1.58
rs2999052	1e-26	EEFSEC	T	1.55
rs417096	7e-25	KIF6 - DAAM2	G	1.43
rs1934179	3e-21	DGKK	A	2.6
rs1858800	1e-18	ZFHX3	T	1.36
rs17208368	3e-15	MTND5P34 - RN7SL841P	A	1.41
rs7811653	2e-14	ZNF619P1 - HMGN1P19	A	1.57
rs16937456	2e-12	XKR9 - EYA1	G	1.4
rs17262815	2e-12	CCDC26	C	1.36
rs10214930	8e-12	TAX1BP1	G	1.33
rs1801085	1e-11	HOXA4, HOXA-AS2, HOXA3	G	1.45
rs10762738	2e-10	KCNMA1-AS1, KCNMA1	G	1.24
rs988958	2e-10	PKDCC - EML4-AS1	G	1.3
rs3743104	6e-10	GREM1	G	1.24
rs13124827	1e-09	FTH1P21 - LINC02272	C	1.23
rs1918690	4e-09	DNAH6	T	1.27
rs11170516	4e-09	SP7 - SP1	G	1.96
rs11749327	9e-09	EXOC3	C	1.25
rs6499755	1e-08	RN7SL841P - IRX6	C	1.22
rs143136847	6e-08	CCDC59	G	2.6
rs17747401	1e-07	ADK	T	1.2
rs4563609	3e-07	LINC02227	A	1.2
rs8045253	6e-07	LINC00917 - FENDRR	C	1.19
rs3812762	1e-06	DENND2B	G	1.2
rs10979	1e-06	PHACTR2	A	1.19

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002563	Geller F	2014	1,006	2,390	Genome-wide association analyses identify variants in developmental genes associated with hypospadias.
GCST000888	van der Zanden LF	2010	436	0	Common variants in DGKK are strongly associated with risk of hypospadias.
GCST90474274	UK Biobank Whole-Genome Sequencing Consortium	2025	288	458,152	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST009672	Chen Z	2019	197	0	Genome-wide association study in Chinese cohort identifies one novel hypospadias risk associated locus at 12q13.13.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	20

MAF distribution

Bucket	Variants
common (>=0.05)	25
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	14
intergenic_variant	5
missense_variant	3
3_prime_UTR_variant	2
regulatory_region_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4554617	X	50460404	A>C	0.312	intron_variant	DGKK	1e-93	Tier 4: intronic/intergenic
rs3816183	2	42788579	T>C	0.246	missense_variant	HAAO	4e-34	Tier 1: coding
rs2999052	3	128173194	T>C	0.262	intron_variant	EEFSEC	1e-26	Tier 4: intronic/intergenic
rs417096	6	39760057	G>A,C,T	0.356	intergenic_variant	KIF6 - DAAM2	7e-25	Tier 4: intronic/intergenic
rs1934179	X	50439186	G>A	0.33	intron_variant	DGKK	3e-21	Tier 4: intronic/intergenic
rs1858800	16	72990377	C>A,G,T	0.332	intron_variant	ZFHX3	1e-18	Tier 4: intronic/intergenic
rs17208368	16	55038095	C>A,T	0.159	intergenic_variant	MTND5P34 - RN7SL841P	3e-15	Tier 4: intronic/intergenic
rs7811653	7	46362671	C>A	0.074	intergenic_variant	ZNF619P1 - HMGN1P19	2e-14	Tier 4: intronic/intergenic
rs16937456	8	71165720	A>G,T	0.124	intron_variant	XKR9 - EYA1	2e-12	Tier 4: intronic/intergenic
rs17262815	8	129478919	T>C	0.154	intron_variant	CCDC26	2e-12	Tier 4: intronic/intergenic
rs10214930	7	27745330	G>A	0.236	intron_variant	TAX1BP1	8e-12	Tier 4: intronic/intergenic
rs1801085	7	27128971	A>C,G,T	0.091	3_prime_UTR_variant	HOXA4, HOXA-AS2, HOXA3	1e-11	Tier 2: splice/UTR
rs10762738	10	76935709	A>G	0.497	intron_variant	KCNMA1-AS1, KCNMA1	2e-10	Tier 4: intronic/intergenic
rs988958	2	42060166	G>A	0.25	regulatory_region_variant	PKDCC - EML4-AS1	2e-10	Tier 3: regulatory
rs3743104	15	32731784	A>C,G,T	0.446	3_prime_UTR_variant	GREM1	6e-10	Tier 2: splice/UTR
rs13124827	4	156419058	C>T	0.47	intron_variant	FTH1P21 - LINC02272	1e-09	Tier 4: intronic/intergenic
rs1918690	2	84679791	T>A,C	0.208	intron_variant	DNAH6	4e-09	Tier 4: intronic/intergenic
rs11170516	12	53358908	G>A	0.216	intergenic_variant	SP7 - SP1	4e-09	Tier 4: intronic/intergenic
rs11749327	5	457146	C>A,T	0.293	intron_variant	EXOC3	9e-09	Tier 4: intronic/intergenic
rs6499755	16	55307223	T>A,C,G	0.367	intron_variant	RN7SL841P - IRX6	1e-08	Tier 4: intronic/intergenic
rs143136847	12	82354560	T>C,G	0.007	missense_variant	CCDC59	6e-08	Tier 1: coding
rs17747401	10	74640406	C>T	0.378	intron_variant	ADK	1e-07	Tier 4: intronic/intergenic
rs4563609	5	158490267	G>A,C	0.35	intron_variant	LINC02227	3e-07	Tier 4: intronic/intergenic
rs8045253	16	86404161	T>C,G	0.348	intergenic_variant	LINC00917 - FENDRR	6e-07	Tier 4: intronic/intergenic
rs3812762	11	8730093	G>A,C	0.325	missense_variant	DENND2B	1e-06	Tier 1: coding
rs10979	6	143568902	G>A	0.331	non_coding_transcript_exon_variant	PHACTR2	1e-06	Tier 4: intronic/intergenic

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
419128	NM_006218.4(PIK3CA):c.278G>A (p.Arg93Gln)	PIK3CA	Pathogenic	criteria provided, multiple submitters, no conflicts
1339465	NM_012330.4(KAT6B):c.1688C>T (p.Pro563Leu)	KAT6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1339469	NM_020369.3(FSCN3):c.1154A>G (p.Asn385Ser)	FSCN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339466	NM_018026.4(PACS1):c.2146G>A (p.Gly716Arg)	PACS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339464	NM_014390.4(SND1):c.2597G>A (p.Arg866His)	SND1	Uncertain significance	criteria provided, single submitter
2570663	NM_172230.3(SYVN1):c.38C>T (p.Ala13Val)	SYVN1	Uncertain significance	criteria provided, single submitter
2570664	NM_172230.3(SYVN1):c.68A>G (p.Tyr23Cys)	SYVN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339468	NM_004626.3(WNT11):c.922A>G (p.Ser308Gly)	WNT11	Uncertain significance	criteria provided, single submitter
1339467	NM_001300939.2(WNT8A):c.142A>G (p.Ile48Val)	WNT8A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 30 · 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.

Gene	Classification	Inheritance	Disease	Records
BMP7	Limited	Autosomal dominant	hypospadias	5
HOXB6	Limited	Autosomal dominant	hypospadias

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IRX5	Orphanet:314555	Facial dysmorphism-ocular anomalies-osteopenia-intellectual disability-dental anomalies syndrome
SP7	Orphanet:1513	Craniodiaphyseal dysplasia
SP7	Orphanet:216820	Osteogenesis imperfecta type 4
KAT6B	Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type
KAT6B	Orphanet:85201	Genitopatellar syndrome
DAAM2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
GREM1	Orphanet:157794	Hereditary mixed polyposis syndrome
PACS1	Orphanet:329224	Schuurs-Hoeijmakers syndrome
EYA1	Orphanet:107	BOR syndrome
EYA1	Orphanet:2792	Otofaciocervical syndrome
EYA1	Orphanet:52429	Branchiootic syndrome
AK1	Orphanet:86817	Hemolytic anemia due to adenylate kinase deficiency
HAAO	Orphanet:521438	Congenital vertebral-cardiac-renal anomalies syndrome
KCNMA1	Orphanet:664438	Gingival fibromatosis-aortic root dilatation-facial dysmorphism-intellectual disability syndrome
KCNMA1	Orphanet:79137	Generalized epilepsy-paroxysmal dyskinesia syndrome
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CA	Orphanet:714737	Diffuse capillary malformation with overgrowth
PIK3CA	Orphanet:90308	Capillary-lymphatic-venous malformation with segmental distribution
PIK3CA	Orphanet:99802	Hemimegalencephaly

Cohort genes → proteins

35 cohort genes, 33 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	25
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMP7	HGNC:1074	ENSG00000101144	P18075	Bone morphogenetic protein 7	gencc
HOXB6	HGNC:5117	ENSG00000108511	P17509	Homeobox protein Hox-B6	gencc
SP1	HGNC:11205	ENSG00000185591	P08047	Transcription factor Sp1	gwas
DENND2B	HGNC:11350	ENSG00000166444	P78524	DENN domain-containing protein 2B	gwas
TAX1BP1	HGNC:11575	ENSG00000106052	Q86VP1	Tax1-binding protein 1	gwas
WNT11	HGNC:12776	ENSG00000085741	O96014	Protein Wnt-11	clinvar
WNT8A	HGNC:12788	ENSG00000061492	Q9H1J5	Protein Wnt-8a	clinvar
IRX5	HGNC:14361	ENSG00000176842	P78411	Iroquois-class homeodomain protein IRX-5	gwas
IRX6	HGNC:14675	ENSG00000159387	P78412	Iroquois-class homeodomain protein IRX-6	gwas
SP7	HGNC:17321	ENSG00000170374	Q8TDD2	Transcription factor Sp7	gwas
KAT6B	HGNC:17582	ENSG00000156650	Q8WYB5	Histone acetyltransferase KAT6B	clinvar
DAAM2	HGNC:18143	ENSG00000146122	Q86T65	Disheveled-associated activator of morphogenesis 2	gwas
GREM1	HGNC:2001	ENSG00000166923	O60565	Gremlin-1	gwas
SYVN1	HGNC:20738	ENSG00000162298	Q86TM6	E3 ubiquitin-protein ligase synoviolin	clinvar
EEFSEC	HGNC:24614	ENSG00000132394	P57772	Selenocysteine-specific elongation factor	gwas
CCDC59	HGNC:25005	ENSG00000133773	Q9P031	Thyroid transcription factor 1-associated protein 26	gwas
PKDCC	HGNC:25123	ENSG00000162878	Q504Y2	Extracellular tyrosine-protein kinase PKDCC	gwas
CCDC26	HGNC:28416	ENSG00000229140		CCDC26 long non-coding RNA	gwas
DNAH6	HGNC:2951	ENSG00000115423	Q9C0G6	Dynein axonemal heavy chain 6	gwas
PACS1	HGNC:30032	ENSG00000175115	Q6VY07	Phosphofurin acidic cluster sorting protein 1	clinvar
EXOC3	HGNC:30378	ENSG00000180104	O60645	Exocyst complex component 3	gwas
SND1	HGNC:30646	ENSG00000197157	Q7KZF4	Staphylococcal nuclease domain-containing protein 1	clinvar
EBF1	HGNC:3126	ENSG00000164330	Q9UH73	Transcription factor COE1	gwas
DGKK	HGNC:32395	ENSG00000274588	Q5KSL6	Diacylglycerol kinase kappa	gwas
EYA1	HGNC:3519	ENSG00000104313	Q99502	Protein phosphatase EYA1	gwas
AK1	HGNC:361	ENSG00000106992	P00568	Adenylate kinase isoenzyme 1	gwas
FSCN3	HGNC:3961	ENSG00000106328	Q9NQT6	Fascin-3	clinvar
FENDRR	HGNC:43894	ENSG00000268388		FOXF1 adjacent non-coding developmental regulatory RNA	gwas
HAAO	HGNC:4796	ENSG00000162882	P46952	3-hydroxyanthranilate 3,4-dioxygenase	gwas
HOXA4	HGNC:5105	ENSG00000197576	Q00056	Homeobox protein Hox-A4	gwas
IGFBP3	HGNC:5472	ENSG00000146674	P17936	Insulin-like growth factor-binding protein 3	gwas
KCNMA1	HGNC:6284	ENSG00000156113	Q12791	Calcium-activated potassium channel subunit alpha-1	gwas
ZFHX3	HGNC:777	ENSG00000140836	Q15911	Zinc finger homeobox protein 3	gwas
PDGFC	HGNC:8801	ENSG00000145431	Q9NRA1	Platelet-derived growth factor C	gwas
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP7	Bone morphogenetic protein 7	Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis.
HOXB6	Homeobox protein Hox-B6	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
SP1	Transcription factor Sp1	Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli.
DENND2B	DENN domain-containing protein 2B	May be involved in cytoskeletal organization and tumorogenicity.
TAX1BP1	Tax1-binding protein 1	Ubiquitin-binding adapter that participates in inflammatory, antiviral and innate immune processes as well as selective autophagy regulation.
WNT11	Protein Wnt-11	Ligand for members of the frizzled family of seven transmembrane receptors.
WNT8A	Protein Wnt-8a	Ligand for members of the frizzled family of seven transmembrane receptors.
IRX5	Iroquois-class homeodomain protein IRX-5	Establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene.
IRX6	Iroquois-class homeodomain protein IRX-6	Transcription factor.
SP7	Transcription factor Sp7	Transcriptional activator essential for osteoblast differentiation.
KAT6B	Histone acetyltransferase KAT6B	Histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
DAAM2	Disheveled-associated activator of morphogenesis 2	Key regulator of the Wnt signaling pathway, which is required for various processes during development, such as dorsal patterning, determination of left/right symmetry or myelination in the central nervous system.
GREM1	Gremlin-1	Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop.
SYVN1	E3 ubiquitin-protein ligase synoviolin	E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation.
EEFSEC	Selenocysteine-specific elongation factor	Translation factor required for the incorporation of the rare amino acid selenocysteine encoded by UGA codons.
CCDC59	Thyroid transcription factor 1-associated protein 26	Component of the transcription complexes of the pulmonary surfactant-associated protein-B (SFTPB) and -C (SFTPC).
PKDCC	Extracellular tyrosine-protein kinase PKDCC	Secreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages.
DNAH6	Dynein axonemal heavy chain 6	Force generating protein of respiratory cilia.
PACS1	Phosphofurin acidic cluster sorting protein 1	Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs.
EXOC3	Exocyst complex component 3	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
SND1	Staphylococcal nuclease domain-containing protein 1	Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs.
EBF1	Transcription factor COE1	Key pioneer transcription factor of B-cell specification and commitment.
DGKK	Diacylglycerol kinase kappa	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
EYA1	Protein phosphatase EYA1	Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5.
AK1	Adenylate kinase isoenzyme 1	Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP.
FSCN3	Fascin-3	Acts as an actin bundling protein.
HAAO	3-hydroxyanthranilate 3,4-dioxygenase	Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.
HOXA4	Homeobox protein Hox-A4	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
IGFBP3	Insulin-like growth factor-binding protein 3	Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proliferation, differentiation, and apoptosi…
KCNMA1	Calcium-activated potassium channel subunit alpha-1	Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+).
ZFHX3	Zinc finger homeobox protein 3	Transcriptional regulator which can act as an activator or a repressor.
PDGFC	Platelet-derived growth factor C	Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

Protein-family classification

Druggable: 7 · Difficult: 10 · Unknown: 18 · Druggable fraction: 0.2

Family distribution

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

Family	Genes	Fold	FDR
Transcription factor	10	2.4×	0.035
Kinase	4	3.2×	0.091
Ion channel	1	3.2×	0.451
Other/Unknown	18	0.9×	0.802
Enzyme (other)	2	0.7×	0.802

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMP7	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
HOXB6	Transcription factor	no		HD, Homeobox_Antennapedia_CS, Homeodomain-like_sf
SP1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
DENND2B	Other/Unknown	no		cDENN_dom, dDENN_dom, uDENN_dom
TAX1BP1	Other/Unknown	no		CALCOCO1-like, SKICH, CALCOCO1/2_Zn_UBZ1
WNT11	Other/Unknown	no		Wnt, Wnt_CS, Wnt_C
WNT8A	Other/Unknown	no		Wnt, Wnt8, Wnt_CS
IRX5	Transcription factor	no		HD, Iroquois_homeo, KN_HD
IRX6	Transcription factor	no		HD, Iroquois_homeo, KN_HD
SP7	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
KAT6B	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
DAAM2	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-like
GREM1	Other/Unknown	no		DAN_dom, Cys_knot_C, Gremlin-1/2
SYVN1	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, HRD1_E3_ubiq-ligases
EEFSEC	Other/Unknown	no		T_Tr_GTP-bd_dom, EFTu-like_2, Transl_B-barrel_sf
CCDC59	Other/Unknown	no		Fyv7/TAP26
PKDCC	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, FAM69_kinase_dom
CCDC26	Other/Unknown	no
DNAH6	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dhc_linker
PACS1	Other/Unknown	no		PACS1/2_C, PACS1/2_N
EXOC3	Other/Unknown	no		EXOC3/Sec6, EXOC3/Sec6_C
SND1	Enzyme (other)	yes	3.1.31.1	Thermonucl_AS, Tudor, Staphylococal_nuclease_OB-fold
EBF1	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold
DGKK	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, PH_domain
EYA1	Other/Unknown	no		EYA_dom, EYA, EYA_dom_sf
AK1	Kinase	yes	2.7.4.3	Adenylat/UMP-CMP_kin, AK1/5, P-loop_NTPase
FSCN3	Other/Unknown	no		Actin-crosslinking, Fascin, Fascin-like_dom
FENDRR	Other/Unknown	no
HAAO	Enzyme (other)	yes	1.13.11.6	3hydroanth_dOase, RmlC_Cupin_sf, RmlC-like_jellyroll
HOXA4	Transcription factor	no		HD, Homeobox_Antennapedia_CS, Homeodomain-like_sf
IGFBP3	Other/Unknown	no		Thyroglobulin_1, IGFBP-like, Growth_fac_rcpt_cys_sf
KCNMA1	Ion channel	yes		RCK_N, K_chnl_BK_asu, Ion_trans_dom
ZFHX3	Transcription factor	no		HD, Matrin/U1-like-C_Znf_C2H2, Homeodomain-like_sf
PDGFC	Other/Unknown	no		PDGF/VEGF_dom, CUB_dom, Cystine-knot_cytokine
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	35
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	3
apex of heart	3
tibia	3
ventricular zone	2
left uterine tube	2
oocyte	2
secondary oocyte	2
primordial germ cell in gonad	2
skin of abdomen	2
hindlimb stylopod muscle	2
male germ line stem cell (sensu Vertebrata) in testis	2
cortical plate	2
sural nerve	2
mucosa of stomach	2
stromal cell of endometrium	2
body of pancreas	2
right lobe of liver	2
gastrocnemius	2
calcaneal tendon	2
synovial joint	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP7	243	broad	marker	pigmented layer of retina, ventricular zone, endometrium epithelium
HOXB6	170	ubiquitous	marker	corpus epididymis, seminal vesicle, metanephros cortex
SP1	264	ubiquitous	marker	nipple, trabecular bone tissue, skin of hip
DENND2B	278	ubiquitous	marker	body of uterus, left uterine tube, right uterine tube
TAX1BP1	301	ubiquitous	marker	secondary oocyte, oocyte, bronchial epithelial cell
WNT11	178	broad	marker	omental fat pad, peritoneum, adipose tissue of abdominal region
WNT8A	33	tissue_specific	marker	primordial germ cell in gonad, pancreatic ductal cell, tibialis anterior
IRX5	163	broad	marker	upper leg skin, bronchial epithelial cell, skin of abdomen
IRX6	95	tissue_specific	marker	apex of heart, skin of abdomen, hindlimb stylopod muscle
SP7	46	tissue_specific	yes	primordial germ cell in gonad, tibia, male germ line stem cell (sensu Vertebrata) in testis
KAT6B	140	ubiquitous	yes	cortical plate, ventricular zone, sural nerve
DAAM2	276	ubiquitous	marker	corpus callosum, middle frontal gyrus, inferior vagus X ganglion
GREM1	126	ubiquitous	marker	stromal cell of endometrium, gall bladder, mucosa of stomach
SYVN1	255	ubiquitous	marker	ileal mucosa, body of pancreas, right lobe of liver
EEFSEC	135	ubiquitous	yes	apex of heart, heart left ventricle, gastrocnemius
CCDC59	289	ubiquitous	marker	secondary oocyte, oocyte, tendon of biceps brachii
PKDCC	238	ubiquitous	marker	right ovary, left ovary, left uterine tube
CCDC26	160	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium, bone marrow cell
DNAH6	171	broad	marker	epithelium of bronchus, bronchial epithelial cell, bronchus
PACS1	262	ubiquitous	marker	cortical plate, minor salivary gland, granulocyte
EXOC3	288	ubiquitous	marker	mucosa of transverse colon, adenohypophysis, sural nerve
SND1	292	ubiquitous	marker	body of pancreas, stromal cell of endometrium, islet of Langerhans
EBF1	251	ubiquitous	marker	synovial joint, layer of synovial tissue, calcaneal tendon
DGKK	45	tissue_specific	marker	cardiac muscle of right atrium, left ventricle myocardium, kidney epithelium
EYA1	205	broad	marker	choroid plexus epithelium, urethra, mucosa of paranasal sinus
AK1	144	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
FSCN3	162	tissue_specific	marker	sperm, male germ cell, left testis
FENDRR	188	broad	marker	right lung, muscle layer of sigmoid colon, lower esophagus muscularis layer
HAAO	178	broad	marker	right lobe of liver, liver, descending thoracic aorta
HOXA4	111	broad	yes	esophagogastric junction muscularis propria, mucosa of stomach, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIK3CA	5,157
SP1	4,275
AK1	3,526
IGFBP3	3,213
BMP7	3,134
TAX1BP1	3,089
SND1	2,910
KCNMA1	2,606
SP7	2,310
EEFSEC	2,279

Intra-cohort edges

A	B	Sources
BMP7	GREM1	string_interaction
DGKK	HOXA4	string_interaction
IRX5	IRX6	string_interaction

Structural data

PDB: 18 · AlphaFold-only: 15 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3CA	P42336	135
KCNMA1	Q12791	36
SP1	P08047	11
SND1	Q7KZF4	11
TAX1BP1	Q86VP1	10
SYVN1	Q86TM6	7
AK1	P00568	5
BMP7	P18075	4
EEFSEC	P57772	4
KAT6B	Q8WYB5	3
HAAO	P46952	3
ZFHX3	Q15911	3
GREM1	O60565	2
EBF1	Q9UH73	2
WNT8A	Q9H1J5	1
DNAH6	Q9C0G6	1
PACS1	Q6VY07	1
IGFBP3	P17936	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FSCN3	Q9NQT6	92.19
WNT11	O96014	90.35
EXOC3	O60645	88.79
PKDCC	Q504Y2	82.96
DAAM2	Q86T65	80.02
PDGFC	Q9NRA1	76.30
CCDC59	Q9P031	74.09
DGKK	Q5KSL6	66.68
EYA1	Q99502	66.68
HOXB6	P17509	66.67
HOXA4	Q00056	63.88
DENND2B	P78524	58.86
IRX6	P78412	55.29
IRX5	P78411	55.14
SP7	Q8TDD2	52.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 182. Enrichment computed across 35 evidence-associated genes (26 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 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the ureteric bud	3	57.3×	0.003	WNT11, GREM1, EYA1
WNT ligand biogenesis and trafficking	2	32.5×	0.154	WNT11, WNT8A
Acetylcholine inhibits contraction of outer hair cells	1	87.8×	0.162	KCNMA1
MET activates PI3K/AKT signaling	1	73.2×	0.162	PIK3CA
Activated NTRK3 signals through PI3K	1	73.2×	0.162	PIK3CA
RUNX3 regulates CDKN1A transcription	1	62.8×	0.162	ZFHX3
Activated NTRK2 signals through PI3K	1	62.8×	0.162	PIK3CA
Signaling by LTK in cancer	1	62.8×	0.162	PIK3CA
Hh mutants abrogate ligand secretion	1	54.9×	0.162	SYVN1
PI3K/AKT activation	1	48.8×	0.162	PIK3CA
Ca2+ activated K+ channels	1	43.9×	0.162	KCNMA1
Nef mediated downregulation of MHC class I complex cell surface expression	1	43.9×	0.162	PACS1
Transcriptional regulation of brown and beige adipocyte differentiation	1	43.9×	0.162	BMP7
IRS-mediated signalling	1	39.9×	0.162	PIK3CA
PI3K events in ERBB4 signaling	1	39.9×	0.162	PIK3CA
Regulation of CDH11 gene transcription	1	39.9×	0.162	SP1
Co-stimulation by ICOS	1	39.9×	0.162	PIK3CA
Signaling by FGFR4 in disease	1	36.6×	0.162	PIK3CA
TP53 Regulates Transcription of Death Receptors and Ligands	1	36.6×	0.162	IGFBP3
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	36.6×	0.162	PIK3CA
Positive Regulation of CDH1 Gene Transcription	1	36.6×	0.162	SP1
NFE2L2 regulating tumorigenic genes	1	36.6×	0.162	SP1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	33.8×	0.162	PIK3CA
Signaling by PDGFRA extracellular domain mutants	1	33.8×	0.162	PIK3CA
Signaling by LTK	1	33.8×	0.162	PIK3CA
Nitric oxide stimulates guanylate cyclase	1	31.4×	0.162	KCNMA1
RUNX2 regulates bone development	1	31.4×	0.162	SP7
Regulation of CDH11 Expression and Function	1	31.4×	0.162	SP1
Tryptophan catabolism	1	29.3×	0.162	HAAO
Signaling by FLT3 ITD and TKD mutants	1	29.3×	0.162	PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 32 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
osteoblast differentiation	5	18.9×	0.002	BMP7, WNT11, SP7, SND1, IGFBP3
cellular response to zinc ion starvation	2	150.5×	0.009	SP1, SP7
embryonic skeletal system morphogenesis	3	36.7×	0.009	EYA1, HOXA4, HOXB6
positive regulation of transcription by RNA polymerase II	9	4.2×	0.017	BMP7, SP1, WNT8A, SP7, KAT6B, GREM1, EYA1, HOXA4 (+1 more)
secondary palate development	2	75.2×	0.020	WNT11, WNT8A
neuron differentiation	4	12.5×	0.020	WNT11, WNT8A, IRX5, IRX6
cell development	2	55.4×	0.031	IRX5, IRX6
pharyngeal system development	2	50.1×	0.032	BMP7, EYA1
regulation of neuron differentiation	2	45.8×	0.032	EYA1, ZFHX3
positive regulation of DNA-templated transcription	6	5.2×	0.032	BMP7, SP1, WNT11, IRX6, KAT6B, ZFHX3
response to muscle inactivity	1	526.6×	0.036	PIK3CA
quinolinate metabolic process	1	526.6×	0.036	HAAO
otic vesicle morphogenesis	1	526.6×	0.036	EYA1
negative regulation of mesenchymal cell apoptotic process involved in nephron morphogenesis	1	526.6×	0.036	BMP7
mesenchymal cell apoptotic process involved in nephron morphogenesis	1	526.6×	0.036	BMP7
response to butyrate	1	526.6×	0.036	PIK3CA
cellular response to wortmannin	1	526.6×	0.036	SP1
positive regulation of hydrogen sulfide biosynthetic process	1	526.6×	0.036	SP1
protein localization to phagocytic vesicle	1	526.6×	0.036	TAX1BP1
metanephros development	2	31.9×	0.036	BMP7, EYA1
negative regulation of bone remodeling	1	263.3×	0.041	GREM1
cloacal septation	1	263.3×	0.041	WNT11
negative regulation of glomerular mesangial cell proliferation	1	263.3×	0.041	BMP7
nephrogenic mesenchyme morphogenesis	1	263.3×	0.041	BMP7
negative regulation of bone trabecula formation	1	263.3×	0.041	GREM1
regulation of locomotor rhythm	1	263.3×	0.041	ZFHX3
regulation of non-canonical Wnt signaling pathway	1	263.3×	0.041	DAAM2
primary heart field specification	1	175.5×	0.041	WNT11
negative regulation of striated muscle cell apoptotic process	1	175.5×	0.041	BMP7
neural fold elevation formation	1	175.5×	0.041	BMP7

Therapeutics

Drugs indicated for this disease

0 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetaminophen	Phase 3 (in late-stage trials)
Ibuprofen	Phase 3 (in late-stage trials)
Oxycodone	Phase 3 (in late-stage trials)
Promestriene	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Atropine, Bupivacaine, Dextrose, Epinephrine, Fentanyl, Neostigmine, Sodium Chloride.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 32

Druggability breadth: 11 of 35 evidence-associated genes (31%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

Symbol	Example approved molecule
KCNMA1	CANNABIDIOL
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3CA	67	4
KCNMA1	2	4
SP1	1	2
BMP7	0	0
HOXB6	0	0
DENND2B	0	0
TAX1BP1	0	0
WNT11	0	0
WNT8A	0	0
IRX5	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANNABIDIOL	4	KCNMA1
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA
MIDOSTAURIN	4	PIK3CA
FLINDOKALNER	3	KCNMA1
DACTOLISIB	3	PIK3CA
BUPARLISIB	3	PIK3CA
RESVERATROL	3	PIK3CA
IPATASERTIB	3	PIK3CA
TASELISIB	3	PIK3CA
EPIGALOCATECHIN GALLATE	3	PIK3CA
GEDATOLISIB	3	PIK3CA
LESTAURTINIB	3	PIK3CA
SEPANTRONIUM BROMIDE	2	SP1
OMIPALISIB	2	PIK3CA
VISTUSERTIB	2	PIK3CA
FIMEPINOSTAT	2	PIK3CA
EGANELISIB	2	PIK3CA
BERZOSERTIB	2	PIK3CA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
KCNMA1	94	Binding:91, Functional:2, Toxicity:1
KAT6B	22	Binding:20, Functional:2
SP1	10	Binding:8, ADMET:2
SND1	7	Binding:7
HAAO	4	Binding:4
AK1	3	Binding:3
IGFBP3	3	Binding:3
DGKK	2	Binding:2
SYVN1	1	Binding:1
EXOC3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT6B	2.3.1.48	histone acetyltransferase
SND1	3.1.31.1	micrococcal nuclease
DGKK	2.7.1.107	diacylglycerol kinase (ATP)
AK1	2.7.4.3	adenylate kinase
HAAO	1.13.11.6	3-hydroxyanthranilate 3,4-dioxygenase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 33; 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.

Compound	Max phase	Cohort target (bioactivity)
CANNABIDIOL	4	KCNMA1
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA
MIDOSTAURIN	4	PIK3CA
FLINDOKALNER	3	KCNMA1
DACTOLISIB	3	PIK3CA
BUPARLISIB	3	PIK3CA
RESVERATROL	3	PIK3CA
IPATASERTIB	3	PIK3CA
TASELISIB	3	PIK3CA
EPIGALOCATECHIN GALLATE	3	PIK3CA
GEDATOLISIB	3	PIK3CA
LESTAURTINIB	3	PIK3CA
SEPANTRONIUM BROMIDE	2	SP1
OMIPALISIB	2	PIK3CA
VISTUSERTIB	2	PIK3CA
FIMEPINOSTAT	2	PIK3CA
EGANELISIB	2	PIK3CA
BERZOSERTIB	2	PIK3CA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	KCNMA1, PIK3CA
B	Phased (≥1) drug, not yet approved	1	SP1
C	Druggable family + PDB, no drug	3	SND1, AK1, HAAO
D	Druggable family + AlphaFold only, no drug	2	PKDCC, DGKK
E	Difficult family or no structure, no drug	27	BMP7, HOXB6, DENND2B, TAX1BP1, WNT11, WNT8A, IRX5, IRX6, SP7, KAT6B (+17 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BMP7	0	—
HOXB6	0	—
DENND2B	0	—
TAX1BP1	0	—
WNT11	0	—
WNT8A	0	—
IRX5	0	—
IRX6	0	—
SP7	0	—
KAT6B	22	—
DAAM2	0	—
GREM1	0	—
SYVN1	1	—
EEFSEC	0	—
CCDC59	0	—
PKDCC	0	—
CCDC26	0	—
DNAH6	0	—
PACS1	0	—
EXOC3	1	—
SND1	7	—
EBF1	0	—
DGKK	2	—
EYA1	0	—
AK1	3	—
FSCN3	0	—
FENDRR	0	—
HAAO	4	—
HOXA4	0	—
IGFBP3	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 88.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	70
PHASE4	8
PHASE3	4
PHASE2/PHASE3	2
PHASE1/PHASE2	1
PHASE2	1
EARLY_PHASE1	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07240649	PHASE4	NOT_YET_RECRUITING	Outcomes From Hyperbaric Oxygen (HBO2) Treatment for Emerging Indications
NCT02848157	PHASE4	COMPLETED	Effects of Dexmedetomidine as Adjunct to Pudendal Block for Pediatric Penile Surgery
NCT02861950	PHASE4	COMPLETED	Does Caudal Block Increase the Incidence of Urethrocutaneous Fistula Formation Following Hypospadias Repair in Infants?
NCT03902249	PHASE4	COMPLETED	Effect of Intravenous Dexamethasone With Pudendal Nerve Block on Postoperative Pain in Pediatric Hypospadias Repair
NCT05708989	PHASE4	WITHDRAWN	Caudal vs. Pudendal Block in Peds GU
NCT05837000	PHASE4	UNKNOWN	Dexmedetomidine, Ketamine and Magnesium Sulphate in Caudal Block for Hypospadias Repair
NCT05922605	PHASE4	UNKNOWN	Analgesic Effects of Caudal S-ketamine for Supplementation of Ropivacaine Caudal Analgesia in Children With Hypospadias
NCT07121764	PHASE4	COMPLETED	Postoperative Pain Relief in Children: Comparing Caudal Bupivacaine Alone Versus Bupivacaine With Dexmedetomidine for Infra-Umbilical Surgeries Under General Anesthesia
NCT07197203	PHASE3	NOT_YET_RECRUITING	Comparison of Caudal Block and Sacral Erector Spinae Plane Block With Dexmedetomidine in Pediatric Penile Hypospadias Repair
NCT01370798	PHASE3	COMPLETED	Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications
NCT02752308	PHASE2/PHASE3	COMPLETED	Effectiveness of Caudal Epidural Block on Intraoperative Blood Loss During Hypospadias Repair
NCT04423107	PHASE3	UNKNOWN	Assessment of Postop Hypospadias Pain
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT04876976	PHASE2/PHASE3	COMPLETED	Isoamyl 2-Cyanoacrylate in the Urethro-cutaneous Fistula Repair
NCT05093166	PHASE1/PHASE2	TERMINATED	Clinical Trial to Assess the Safety and Efficacy of Investigational Product in Patients Due to Hypospadias Treatment Failure
NCT05253456	PHASE2	COMPLETED	Modified Second Layer Repair for Distal Penile Hypospadias
NCT04479371	PHASE1	WITHDRAWN	Liposomal Bupivacaine vs Standard Penile Block for Hypospadias Repair
NCT04196400	EARLY_PHASE1	UNKNOWN	The Role of Local Long Acting Corticosteroid Injection in Hypospadias Surgery.
NCT02096159	Not specified	ACTIVE_NOT_RECRUITING	Prophylactic Antibiotics or Placebo After Hypospadias Repair
NCT03102554	Not specified	ENROLLING_BY_INVITATION	Genetics of Differences of Sex Development and Hypospadias
NCT03698721	Not specified	NOT_YET_RECRUITING	Urothelium Tissue Engineering Using Biopsies From Transurethral Resection of Prostate
NCT05936853	Not specified	ACTIVE_NOT_RECRUITING	The EPigenetic Consequences in Children of Intravenous vs Volatile Anaesthesia for Surgery (EPIVA)
NCT06405763	Not specified	RECRUITING	Snodgrass Versus Grafted Snodgrass Repair in Narrow Urethral Plate in Distal Penile Hypospadias
NCT06410482	Not specified	NOT_YET_RECRUITING	Analgesia in Pediatric Hypospadias Surgeries
NCT06417060	Not specified	RECRUITING	Caudal Anesthesia Versus Local Anesthesia in Hypospadias
NCT06520423	Not specified	ACTIVE_NOT_RECRUITING	Effectiveness of Urethral Stent Irrigation in Preventing Surgical Site Infections in Adolescents With Hypospadias
NCT06628375	Not specified	RECRUITING	A Multimodal Study of the Relationship Between Exposure to Endocrine Disruptors and Occurrence of Hypospadias - HYPOLLUT
NCT06832280	Not specified	RECRUITING	Improving Parental Support in Hypospadias Care
NCT06966375	Not specified	RECRUITING	Worldwide Yearly Screening for Hypospadias
NCT06989593	Not specified	RECRUITING	Breaking Silence Through Story: A Narrative Medicine Intervention for Parents of Children With Urogenital Conditions
NCT07017842	Not specified	RECRUITING	PREDICT-H Study: Prospective Research on Essential Determinants Influencing Complication Trends in Hypospadias - a Landmark Prospective Multicenter Cohort Study Aimed at Improving Outcome Prediction in Hypospadias Surgery
NCT07045545	Not specified	ENROLLING_BY_INVITATION	A Multicenter Randomized Controlled Trial Comparing Platelet-Rich Fibrin and Ventral Dartos Flap as Intermediate Layers in Tabularized Incised Plate (TIP) Urethroplasty for Distal Hypospadias With Mild Penile Curvature
NCT07086963	Not specified	RECRUITING	Is Dorsal Inlay Graft (DIG) With TIP Repair Superior to TIP Alone for Primary Hypospadias?
NCT07099560	Not specified	RECRUITING	Ultrasound Guided Sacral Erector Spinae Plane Block Versus Ultrasound Guided Caudal Block in Pediatric Undergoing Hypospadias Surgery
NCT07319780	Not specified	RECRUITING	Fibrin-Enhanced TIP Versus Grafted TIP Urethroplasty in Distal Hypospadias
NCT07404722	Not specified	NOT_YET_RECRUITING	Urethral Plate Flap vs. Tunica Vaginalis Flap for Residual Severe Ventral Curvature in Hypospadias
NCT07426731	Not specified	RECRUITING	Comparison of Sacral ESP Block and Dorsal Penile Nerve Block in Pediatric Hypospadias Surgery
NCT01762007	Not specified	WITHDRAWN	The Change of the Detrusor Thickness After Hypospadias Repair - Comparison With the Normal Control Group
NCT01875640	Not specified	COMPLETED	Decision Support for Parents Receiving Information About Child’s Rare Disease
NCT02040389	Not specified	COMPLETED	Visual Guidelines and Tutoring in Pediatric Urological Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NEOSTIGMINE	4	4
ROPIVACAINE	4	2
ATROPINE	4	1
BUPIVACAINE	4	1
ESKETAMINE	4	1
MAGNESIUM SULFATE	4	1
OXYGEN	4	1
MECRYLATE	3	1
PROMESTRIENE	3	1
CHEMBL4557433	0	1