Polycystic ovary syndrome

disease
On this page

Also known as PCOSPCOS1polycystic ovarian diseasepolycystic ovariespolycystic ovary syndrome 1Stein-Leventhal syndrome

Summary

Polycystic ovary syndrome (MONDO:0008487) is a disease with 52 cohort genes (147 GWAS associations across 34 studies) and 830 clinical trials. The dominant Reactome pathway is Hormone ligand-binding receptors (3 cohort genes). Top therapeutic interventions include clomiphene, metformin, and berberine.

At a glance

  • Cohort genes: 52
  • GWAS associations: 147
  • Clinical trials: 830

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namepolycystic ovary syndrome
Mondo IDMONDO:0008487
EFOEFO:0000660
MeSHD011085
OMIM184700
Orphanet3185
DOIDDOID:11612
ICD-10-CME28.2
ICD-111213633323
NCITC26862
SNOMED CT69878008
UMLSC0032460
MedGen10836
Is cancer (heuristic)no

Also known as: PCOS · PCOS1 · polycystic ovarian disease · polycystic ovaries · polycystic ovary syndrome · polycystic ovary syndrome 1 · Stein-Leventhal syndrome

Data availability: 147 GWAS associations (34 studies) · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic diseasepolycystic ovary syndrome

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, infantile spasms, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, Usher syndrome, obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome, CREST syndrome, Sheehan syndrome, polymyalgia rheumatica, autoinflammatory syndrome, neuroleptic malignant syndrome, pituitary stalk interruption syndrome, monosomy 13q34, ring chromosome 13, 48,XXXY syndrome, 49,XXXXY syndrome, hereditary continuous muscle fiber activity, Eisenmenger syndrome, Robinow syndrome, Ehlers-Danlos syndrome, hypoplastic right heart syndrome, shone complex, 48,XYYY syndrome, subcortical band heterotopia, complex regional pain syndrome type 2, faciodigitogenital syndrome, neoplastic syndrome, paraneoplastic syndrome, post-infectious syndrome, Achard-Thiers syndrome, acral dysostosis dyserythropoiesis syndrome, agnathia-microstomia-synotia, Aksu von Stockhausen syndrome, Aloi Tomasini Isaia syndrome, temporomandibular joint dysfunction syndrome, Apert-like polydactyly syndrome, arakawa syndrome 2, arena syndrome, Arnold stickler bourne syndrome, baetz-greenwalt syndrome, bagatelle Cassidy syndrome, baker Vinters syndrome, bobble-head doll syndrome, Boerhaave syndrome, Cantu Sanchez-Corona Fragoso syndrome, Cantu Sanchez-Corona Hernandez syndrome, carbon baby syndrome, Carnevale hernandez castillo syndrome, Cartwright Nelson Fryns syndrome, Charles bonnet syndrome, Parinaud syndrome, corticobasal degeneration disorder, hair defect with photosensitivity and intellectual disability syndrome, AIDS dysmorphic syndrome, congenital acardia, acute lymphoblastic leukemia congenital sporadic aniridia, aglossia and situs inversus, agyria pachygyria polymicrogyria, agyria-pachygyria type 1, Ahumada Del Castillo syndrome, alopecia congenita keratosis palmoplantaris, alpha-mannosidosis type 1, aluminosis, Mauriac syndrome, ankle defects short stature, ankyloblepharon filiforme imperforate anus, annular constricting bands, anophthalmia cleft palate micrognathia, anophthalmia esophageal atresia cryptorchidism, anotia facial palsy cardiac defect, aortic dissection lentiginosis, childhood aortic valve stenosis, arthrogryposis IUGR thoracic dystrophy, arthrogryposis multiplex congenita CNS calcification, arthrogryposis spinal muscular atrophy, asternia, atlanto-axial fusion, atrophoderma of Pierini and Pasini, Barnicoat Baraitser syndrome, Basedow’s coma, BD syndrome, Beardwell syndrome, bhaskar jagannathan syndrome, bidirectional tachycardia, bilirubin induced brain injury in the newborn, blepharo naso facial syndrome van Maldergem type, bone dysplasia corpus callosum agenesis, brachydactyly absence of distal phalanges, brachydactyly anonychia, brachydactyly small stature face anomalies, brachydactyly tibial hypoplasia, brittle bone syndrome lethal type, bronchiectasis oligospermia, Brunsting-Perry syndrome, bruyn scheltens syndrome, burn goodship syndrome, camptodactyly joint contractures and facial skeletal dysplasia, camptodactyly vertebral fusion, Cantu Sanchez-Corona Garcia-Cruz syndrome, cardiac hydatid cysts with intracavitary expansion, cardioencephalomyopathy, cardiofacial syndrome short limbs, cardiomelic syndrome stratton Koehler type, cardiomyopathy and deafness due to tRNA lysine gene mutation, cardiomyopathy diabetes deafness, cardiomyopathy hypogonadism collagenoma syndrome, cardiomyopathy hypogonadism metabolic anomalies, cardiomyopathy spherocytosis, carpo tarsal osteolysis recessive, autosomal dominant cataract, cataract skeletal anomalies, cennamo gangemi syndrome, cerebellar agenesis, cerebello-olivary atrophy, cerebral calcification cerebellar hypoplasia, cerebral calcifications opalescent teeth phosphaturia, oculo digital syndrome, chondrodysplasia, choreoacanthocytosis amyotrophic, chorioretinopathy dominant form microcephaly, Christian Demyer Franken syndrome, Christian Johnson angenieta syndrome, chromosome 3 duplication syndrome, chronic demyelinizing neuropathy with IgM monoclonal, ciliary dyskinesia-bronchiectasis, circumscribed cutaneous aplasia of the vertex, circumscribed disseminated keratosis Jadassohn lew type, cleft lip and palate malrotation cardiopathy, cleft lip and/or palate with mucous cysts of lower, cleft lip palate dysmorphism kumar type, cleft lip palate intellectual disability corneal opacity, cleft lip palate oligodontia syndactyly pili torti, cleft lip palate pituitary deficiency, cleft lip palate-tetraphocomelia, cleft lower lip cleft lateral canthi chorioretinal, cleft palate cardiac defect ectrodactyly, cleft palate colobomata radial synostosis deafness, cleft palate heart disease polydactyly absent tibia, cleft tongue, coarse face hypotonia constipation, Cohen Lockood Wyborney syndrome, type 2 collagenopathy, Collins-Sakati syndrome, coloboma porencephaly hydronephrosis, colobomata unilobar lung heart defect, colonic malakoplakia, Colver Steer Godman syndrome, Combarros Calleja Leno syndrome, complement receptor deficiency, congenital absence of the sternocleidomastoid muscle, congenital amputation, congenital aneurysms of the great vessels, congenital articular rigidity, congenital benign spinal muscular atrophy dominant, congenital cardiovascular shunt, congenital contractures, congenital craniosynostosis maternal hyperthyroiditis, congenital cystic eye, congenital heart disease ptosis hypodontia craniostosis, congenital heart disease radio ulnar synostosis intellectual disability, congenital mumps, congenital stenosis of cervical medullary canal, Dennis-Fairhurst-Moore syndrome, congenital unilateral pulmonary hypoplasia, congenital vagal hyperreflexivity, Cormier Rustin Munnich syndrome, corneal crystals myopathy neuropathy, corneal dystrophy ichthyosis microcephaly intellectual disability, corneal dystrophy pigmentary anomaly malabsorption, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cortada Koussef Matsumoto syndrome, Cortes Lacassie syndrome, craniofacial and skeletal defects, craniofacial dysostosis arthrogryposis progeroid appearance, craniofrontonasal syndrome Teebi type, craniostenosis with congenital heart disease intellectual disability, crawfurd syndrome, cutis gyratum acanthosis nigricans craniosynostosis, cutis laxa osteoporosis, Davenport-Donlan syndrome, Davis Lafer syndrome, de Hauwere Leroy adriaenssens syndrome, deafness conductive stapedial ear malformation facial palsy, deafness goiter stippled epiphyses, deafness hypospadias metacarpal and metatarsal syndrome, deafness mesenteric diverticula of small bowel neuropathy, deafness peripheral neuropathy arterial disease, deafness progressive cataract autosomal dominant, dermatocardioskeletal syndrome boronne type, dextrocardia with situs inversus, diabetes persistent mullerian ducts, diaphragmatic agenesis radial aplasia omphalocele, diaphragmatic hernia exomphalos corpus callosum agenesis, diaphragmatic hernia upper limb defects, die Smulders droog van dijk syndrome, diomedi bernardi placidi syndrome, diphallus rachischisis imperforate anus, distichiasis heart congenital anomalies, double discordia, double uterus-hemivagina-renal agenesis, Drachtman Weinblatt Sitarz syndrome, Duker-Weiss-Siber syndrome, duodenal atresia tetralogy of fallot, duplication of leg mirror foot, duplication of the thumb unilateral biphalangeal, dupont sellier chochillon syndrome, dwarfism bluish sclerae, dwarfism deafness retinitis pigmentosa, dwarfism lethal type advanced bone age, dwarfism thin bones multiple fractures, dysmorphism cleft palate loose skin, Eagle syndrome, ectrodactyly cardiopathy dysmorphism, Elliott ludman Teebi syndrome, enamel hypoplasia cataract hydrocephaly, encephalocele anencephaly, enchondromatosis dwarfism deafness, Engelhard Yatziv syndrome, enlarged vestibular aqueduct syndrome, epidermal nevus vitamin D resistant rickets, epimetaphyseal dysplasia cataract, epiphyseal dysplasia dysmorphism camptodactyly, esophageal atresia coloboma talipes, extrasystoles short stature hyperpigmentation microcephaly, facial clefting corpus callosum agenesis, facio digito genital syndrome recessive form, facio skeletal genital syndrome rippberger type, familial capillaro-venous leptomeningeal angiomatosis, Dursun syndrome, Faye-Petersen-Ward-Carey syndrome, feigenbaum Bergeron syndrome, Feingold trainer syndrome, fetal brain disruption sequence, fetal enterovirus syndrome, fetal parainfluenza virus type 3 syndrome, fetal phenothiazine syndrome, fibromatosis multiple non ossifying, fibula aplasia complex brachydactyly, fibular hypoplasia scapulo pelvic dysplasia absent, Fitz-Hugh-Curtis syndrome, focal alopecia congenital megalencephaly, focal or multifocal malformations in neuronal migration, foix chavany Marie syndrome, Fontaine farriaux blanckaert syndrome, Fraser Jequier Chen syndrome, Freiberg disease, Friedman Goodman syndrome, frontonasal malformation cloacal exstrophy, frontonasal dysplasia Klippel feil syndrome, frontonasal dysplasia phocomelic upper limbs, Fryns Fabry Remans syndrome, Fryns Smeets Thiry syndrome, Fuchs atrophia gyrata chorioideae et retinae, Fukuda-Miyanomae-Nakata syndrome, Fuqua Berkovitz syndrome, Garret-Tripp syndrome, gas bloat syndrome, Gaucher ichthyosis restrictive dermopathy, gershinibaruch Leibo syndrome, Ghose-Sachdev-Kumar syndrome, gigantism advanced bone age hoarse cry, glossopalatine ankylosis micrognathia ear anomalies, goldstein hutt syndrome, goniodysgenesis intellectual disability short stature, green sandford davison syndrome, grix Blankenship Peterson syndrome, Ho-Kaufman-McAlister syndrome, Jaffer-Beighton syndrome, Judge Misch wright syndrome, Kashani-Strom-Utley syndrome, Kasznica-Carlson-Coppedge syndrome, Katsantoni-Papadakou-Lagoyanni syndrome, Kocher-debre-Semelaigne syndrome, Koone-Rizzo-Elias syndrome, Kozlowski Brown Hardwick syndrome, Kozlowski Ouvrier syndrome, Kozlowski Rafinski Klicharska syndrome, Kozlowski Warren Fisher syndrome, Krauss Herman Holmes syndrome, Krieble Bixler syndrome, Kuster Majewski Hammerstein syndrome, Kuster syndrome, Laugier-Hunziker syndrome, Laurence-Prosser-Rocker syndrome, le Marec-Bracq-Picaud syndrome, levator syndrome, Marinesco-Sjogren-like syndrome, Milner-Khallouf-Gibson syndrome, radio-digito-facial dysplasia, Seckel like syndrome majoor-krakauer type, neonatal aspiration syndrome, muscular fibrosis multifocal obstructed vessels, short stature contractures hypotonia, Alice in Wonderland syndrome, megacystis-microcolon-intestinal hypoperistalsis syndrome, Basilicata-Akhtar syndrome, Liberfarb syndrome, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardiac, facial, and digital anomalies with developmental delay, fibrosis, neurodegeneration, and cerebral angiomatosis, Duane anomaly-myopathy-scoliosis syndrome, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, acute radiation syndrome, monoclonal mast cell activation syndrome, oculocerebrodental syndrome, syndromic congenital sodium diarrhea, congenital brachyesophagus-intrathoracic stomach-vertebral anomalies syndrome, intellectual disability-cardiac anomalies-short stature-joint laxity syndrome, intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome, frontonasal dysplasia-bifid nose-upper limb anomalies syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, diaphragmatic hernia-short bowel-asplenia syndrome, warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome, Cramp-fasciculation syndrome, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, blepharophimosis-intellectual disability syndrome/genitopatellar overlap 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, KLHL7-related cold-induced sweating-like syndrome, KAT6B-related multiple congenital anomalies syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, Ruzicka-Goerz-Anton syndrome, Sammartino-Decreccio syndrome, Samson-Gardner syndrome, Samson-Viljoen syndrome, Sanderson-Fraser syndrome, Sandhaus-Ben-Ami syndrome, prostatic malacoplakia associated with prostatic abscess, Saul-Wilkes-Stevenson syndrome, macrogyria, pseudobulbar palsy and intellectual disability, Schwartz-Cohen-addad-Lambert syndrome, Schlegelberger-Grote syndrome, Schrander-stumpel-Theunissen-Hulsmans syndrome, Saal-Bulas syndrome, Sackey-Sakati-Aur syndrome, Slti-Salem syndrome, Zerres Rietschel Majewski syndrome, Zazam Sheriff Phillips syndrome, Zadik-Barak-Levin syndrome, weinstein kliman scully syndrome, thickened earlobes with conductive deafness from incus-stapes abnormalities, ichthyosis linearis circumflexa, infantile striato thalamic degeneration, Landy-Donnai syndrome, merlob grunebaum reisner syndrome, Pavone Fiumara Rizzo syndrome, pfeiffer rockelein syndrome, Pfeiffer Tietze Welte syndrome, phosphoribosylpyrophosphate synthetase deficiency, piepkorn karp hickok syndrome, podder-tolmie syndrome, pointer syndrome, richieri-costa guion-almeida cohen syndrome, Rubinstein Taybi like syndrome, ruvalcaba churesigaew myhre syndrome, short limb dwarf lethal colavita kozlowski type, Mallory-Weiss syndrome, superior vena cava syndrome, piriformis syndrome, engraftment syndrome, Adams-Stokes syndrome, Leriche syndrome, multiple organ dysfunction syndrome, posterior leukoencephalopathy syndrome, cardio-renal syndrome, Rahman syndrome, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, Lopes-Maciel-Rodan syndrome, Stankiewicz-Isidor syndrome, Skraban-Deardorff syndrome, joint laxity, short stature, and myopia, Sweeney-Cox syndrome, Alkuraya-Kucinskas syndrome, Jaberi-Elahi syndrome, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, hearing impairment and infertile male syndrome, cardiocutaneous syndrome, neonatal diabetes, congenital sensorineural hearing loss and congenital cataracts, cardioectodermal syndrome, cannabinoid hyperemesis syndrome, retrograde cricopharyngeus dysfunction, Zinner syndrome, retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome, IFAP syndrome, DICER1-related tumor predisposition, Roberts-SC phocomelia syndrome, carcinoid syndrome, Bonnevie-Ullrich syndrome, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, RNU4ATAC spectrum disorder, syndromic congenital heart disease, hand-foot syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, gastrointestinal defects and immunodeficiency syndrome 1, achalasia-alacrima syndrome, black locks with albinism and deafness syndrome, Birt-Hogg-Dube syndrome, trigeminal trophic syndrome, developmental and/or epileptic encephalopathy with spike-wave activation in sleep, syndromic microspherophakia, painful legs and moving toes syndrome, congenital aphakia-iris hypoplasia-microphthalmia-microcornea syndrome, hereditary persistence of fetal hemoglobin-intellectual disability syndrome, developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome, primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome, post-cardiac arrest syndrome, early-onset obesity-hyperphagia-severe developmental delay syndrome, hereditary alpha tryptasemia syndrome, KINSSHIP syndrome, developmental delay, hypotrophy, and dysmorphic features without moebius syndrome, breast implant illness, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, craniosynostosis-facial dysmorphism-chiari-1 malformation-developmental and language delay syndrome, MYT1L-related developmental delay-intellectual disability-obesity syndrome, Houge-Janssens syndrome, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, pyoderma gangrenosum-acne-hidradenitis suppurativa-ankylosing spondylitis syndrome, psoriatic arthritis-pyoderma gangrenosum-acne-hidradenitis suppurativa syndrome, megalencephaly-polydactyly syndrome, Leigh syndrome, mitochondrial, auroneurodental syndrome, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, Grisel syndrome, arterial tortuosity-bone fragility syndrome, dialysis disequilibrium syndrome, brain abnormalities-severe developmental delay-facial dysmorphism-intellectual disability syndrome due to MEF2C mutation, Kariminejad neurodevelopmental syndrome, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, Morimoto-Ryu-Malicdan neuromuscular syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, Pan-Chung-Bellen syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, Tayoun-Maawali syndrome, ragopathy, cardiovascular-kidney-metabolic syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Li-Takada-Miyake syndrome, Guillouet-Gordon syndrome, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, RAC2-related combined immunodeficiency-bronchiectasis-cancer-predisposing syndrome, oculovertebral syndrome, Alsahan-Harris syndrome, Ververi-Brady syndrome, Dursun-Ozgul neurodevelopmental syndrome, immune dysregulation, neurodevelopmental defects, and colitis, Harel-Tora neurodevelopmental syndrome, Valence-Farazi cerebellar ataxia syndrome, dyschromatosis, ichthyosis, deafness, and atopic disease, Ramond-Elliott neurodevelopmental syndrome, STAD syndrome, craniosynostosis-scoliosis syndrome, loin pain hematuria syndrome, IRF6-related condition, linkeropathy, NDUFB11-related disorders, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy, antiphospholipid syndrome

Genetics & variants

GWAS landscape

147 GWAS associations across 34 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs80501362e-85FTOA
rs7057029e-26RAB5B - SUOXG1.27
rs22386891e-23GIPRT
rs134294582e-23THADAA1.49
rs124786013e-23THADAC1.39
rs18941161e-22YAP1G1.27
rs70301933e-22DENND1AA0.68
rs22720462e-21HMGA2A1.43
rs134057288e-21LHCGR, STON1-GTF2A1LA1.41
rs178799613e-20CHEK2A0.62
rs24791068e-19DENND1AG1.34
rs108188549e-18DENND1AA1.51
rs1820759392e-16CHEK2G1.69
rs99305016e-15FTOA
rs21785753e-14ERBB4A0.17
rs38024575e-14AOPEPG1.3
rs727535996e-14PROX1T
rs37298531e-13GATA4T1.18
rs12655643e-13CUX2A
rs98442124e-13ADCY5C
rs109933975e-13AOPEPC1.37
rs110310059e-13ARL14EP-DTT0.16
rs22683611e-12MIR548BAHG, FSHRC1.15
rs13515921e-12ERBB4G1.18
rs109383981e-12PRDX4P1 - THAP12P9A
rs120007072e-12DENND1AT0.4
rs39456283e-12DENND1AC1.4
rs8042794e-12GATA4 - NEIL2A0.13
rs108356385e-12ARL14EP-DTT1.81
rs47841654e-11CASC22 - TOX3G1.15

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90134404Liu Q202274,124824,006A genome-wide cross-trait analysis identifies shared loci and causal relationships of type 2 diabetes and glycaemic traits with polycystic ovary syndrome.
GCST90134405Liu Q202274,124824,006A genome-wide cross-trait analysis identifies shared loci and causal relationships of type 2 diabetes and glycaemic traits with polycystic ovary syndrome.
GCST90483500Venkatesh SS202514,467430,267Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.
GCST90134406Liu Q202210,074103,164A genome-wide cross-trait analysis identifies shared loci and causal relationships of type 2 diabetes and glycaemic traits with polycystic ovary syndrome.
GCST90134407Liu Q202210,074103,164A genome-wide cross-trait analysis identifies shared loci and causal relationships of type 2 diabetes and glycaemic traits with polycystic ovary syndrome.
GCST90134408Liu Q202210,074103,164A genome-wide cross-trait analysis identifies shared loci and causal relationships of type 2 diabetes and glycaemic traits with polycystic ovary syndrome.
GCST007089Day F201810,074103,164Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.
GCST003144Day FR20155,18482,759Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome.
GCST90454205Pujol Gualdo N20255,171283,185Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST90558302Burns K20243,018131,986Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic48

MAF distribution

BucketVariants
common (>=0.05)47
low_freq (0.01-0.05)2
rare (<0.01)0
unknown1

Functional consequences

ConsequenceCount
intron_variant42
intergenic_variant6
regulatory_region_variant1
missense_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs80501361653782363C>A0.41intron_variantFTO2e-85Tier 4: intronic/intergenic
rs7057021255996852A>C,G,T0.245regulatory_region_variantRAB5B - SUOX9e-26Tier 3: regulatory
rs22386891945675403T>A,C,G0.43intron_variantGIPR1e-23Tier 4: intronic/intergenic
rs13429458243411699A>C0.09intron_variantTHADA2e-23Tier 4: intronic/intergenic
rs12478601243494369C>T0.29intron_variantTHADA3e-23Tier 4: intronic/intergenic
rs189411611102199908A>C,G,T0.194intron_variantYAP11e-22Tier 4: intronic/intergenic
rs70301939123879973A>C,G0.05intron_variantDENND1A3e-22Tier 4: intronic/intergenic
rs22720461265830681A>C,G,T0.093intron_variantHMGA22e-21Tier 4: intronic/intergenic
rs13405728248751020A>C,G0.24intron_variantLHCGR, STON1-GTF2A1L8e-21Tier 4: intronic/intergenic
rs178799612228725099A>C,G,Tmissense_variantCHEK23e-20Tier 1: coding
rs24791069123762933A>G,T0.22intron_variantDENND1A8e-19Tier 4: intronic/intergenic
rs108188549123684499G>A0.09intron_variantDENND1A9e-18Tier 4: intronic/intergenic
rs1820759392228702388A>G,T0.044intron_variantCHEK22e-16Tier 4: intronic/intergenic
rs99305011653796540A>G0.45intron_variantFTO6e-15Tier 4: intronic/intergenic
rs21785752212527042G>A,T0.15intron_variantERBB43e-14Tier 4: intronic/intergenic
rs3802457994979054G>A,C,T0.096intron_variantAOPEP5e-14Tier 4: intronic/intergenic
rs727535991214007176C>T0.2intron_variantPROX16e-14Tier 4: intronic/intergenic
rs3729853811756807T>C,G0.05intron_variantGATA41e-13Tier 4: intronic/intergenic
rs126556412111270654A>C0.42intron_variantCUX23e-13Tier 4: intronic/intergenic
rs98442123123303023G>C0.41intron_variantADCY54e-13Tier 4: intronic/intergenic
rs10993397994917489C>T0.44intron_variantAOPEP5e-13Tier 4: intronic/intergenic
rs110310051130204809T>C0.15intron_variantARL14EP-DT9e-13Tier 4: intronic/intergenic
rs2268361248974473C>A,G,T0.496intron_variantMIR548BAHG, FSHR1e-12Tier 4: intronic/intergenic
rs13515922212529988C>G0.17intron_variantERBB41e-12Tier 4: intronic/intergenic
rs10938398445184122G>A0.42intergenic_variantPRDX4P1 - THAP12P91e-12Tier 4: intronic/intergenic
rs120007079123820299T>C0.05intron_variantDENND1A2e-12Tier 4: intronic/intergenic
rs39456289123773274T>C0.07intron_variantDENND1A3e-12Tier 4: intronic/intergenic
rs804279811766380A>C,G,T0.26intergenic_variantGATA4 - NEIL24e-12Tier 4: intronic/intergenic
rs108356381130230805G>A,T0.16intron_variantARL14EP-DT5e-12Tier 4: intronic/intergenic
rs47841651652313907T>A,G0.325intron_variantCASC22 - TOX34e-11Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 53 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BMPR1BOrphanet:2098Acromesomelic dysplasia, Grebe type
BMPR1BOrphanet:2639Fibular aplasia-complex brachydactyly syndrome
BMPR1BOrphanet:93384Brachydactyly type C
BMPR1BOrphanet:93388Brachydactyly type A1
BMPR1BOrphanet:93396Brachydactyly type A2
ZFP36L2Orphanet:488191Female infertility due to oocyte meiotic arrest
ZFP36L2Orphanet:675396Epithelioid hemangioma
SUOXOrphanet:99731Isolated sulfite oxidase deficiency
ZBTB16Orphanet:520Acute promyelocytic leukemia
ZBTB16Orphanet:99861Precursor T-cell acute lymphoblastic leukemia
IKZF3Orphanet:67038B-cell chronic lymphocytic leukemia
IKZF3Orphanet:699590Immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency
IKZF3Orphanet:699593Combined immunodeficiency-lymphopenia-cancer predisposing syndrome due to AIOLOS deficiency
LMF1Orphanet:535453Familial lipase maturation factor 1 deficiency
YAP1Orphanet:1473Uveal coloboma-cleft lip and palate-intellectual disability
YAP1Orphanet:157791Epithelioid hemangioendothelioma
WWTR1Orphanet:157791Epithelioid hemangioendothelioma
WWTR1Orphanet:673556Pseudomyogenic hemangioendothelioma
ERBB2Orphanet:213726Serous carcinoma of the corpus uteri
ERBB2Orphanet:2800Extramammary Paget disease
ERBB2Orphanet:388Hirschsprung disease
ERBB2Orphanet:99976Adenocarcinoma of the oesophagus and oesophagogastric junction
ERBB3Orphanet:137776Lethal congenital contracture syndrome type 2
ERBB3Orphanet:388Hirschsprung disease
ERBB4Orphanet:178469Autosomal dominant non-syndromic intellectual disability
ERBB4Orphanet:803Amyotrophic lateral sclerosis
FANCCOrphanet:84Fanconi anemia
FSHBOrphanet:52901Isolated follicle stimulating hormone deficiency
FSHROrphanet:24346,XX gonadal dysgenesis
FSHROrphanet:64739Ovarian hyperstimulation syndrome
GATA4Orphanet:2510718p23.1 microdeletion syndrome
GATA4Orphanet:25151046,XY partial gonadal dysgenesis
GATA4Orphanet:3303Tetralogy of Fallot
GATA4Orphanet:334Hereditary atrial fibrillation
GATA4Orphanet:576232Partial atrioventricular septal defect with ventricular hypoplasia
GATA4Orphanet:99067Complete atrioventricular septal defect with ventricular hypoplasia
GATA4Orphanet:99068Complete atrioventricular septal defect-tetralogy of Fallot
GATA4Orphanet:99103Atrial septal defect, ostium secundum type
HMGA2Orphanet:276148Benign epithelial tumor of salivary glands
HMGA2Orphanet:397590Silver-Russell syndrome due to a point mutation
HMGA2Orphanet:9406312q14 microdeletion syndrome
HMGA2Orphanet:99970Dedifferentiated liposarcoma
HMGA2Orphanet:99971Well-differentiated liposarcoma
INSROrphanet:2297Insulin-resistance syndrome type A
INSROrphanet:263458Hyperinsulinism due to INSR deficiency
INSROrphanet:508Donohue syndrome
INSROrphanet:769Rabson-Mendenhall syndrome
IRF1Orphanet:699615Severe mendelian susceptibility to mycobacterial diseases due to complete IRF1 deficiency
LHCGROrphanet:3000Familial peripheral male-limited precocious puberty
LHCGROrphanet:96265Leydig cell hypoplasia due to complete LH resistance

Cohort genes → proteins

52 cohort genes, 51 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only52

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BMPR1BHGNC:1077ENSG00000138696O00238Bone morphogenetic protein receptor type-1Bgwas
ZFP36L2HGNC:1108ENSG00000152518P47974mRNA decay activator protein ZFP36L2gwas
SOD2HGNC:11180ENSG00000291237P04179Superoxide dismutase [Mn], mitochondrialgwas
SOX8HGNC:11203ENSG00000005513P57073Transcription factor SOX-8gwas
SSTR5HGNC:11334ENSG00000162009P35346Somatostatin receptor type 5gwas
SUOXHGNC:11460ENSG00000139531P51687Sulfite oxidase, mitochondrialgwas
TOX3HGNC:11972ENSG00000103460O15405TOX high mobility group box family member 3gwas
UNC5CHGNC:12569ENSG00000182168O95185Netrin receptor UNC5Cgwas
ZBTB16HGNC:12930ENSG00000109906Q05516Zinc finger and BTB domain-containing protein 16gwas
IKZF3HGNC:13178ENSG00000161405Q9UKT9Zinc finger protein Aiolosgwas
FIGNHGNC:13285ENSG00000182263Q5HY92Fidgetingwas
AOPEPHGNC:1361ENSG00000148120Q8N6M6Aminopeptidase Ogwas
LMF1HGNC:14154ENSG00000103227Q96S06Lipase maturation factor 1gwas
YAP1HGNC:16262ENSG00000137693P46937Transcriptional coactivator YAP1gwas
CDH10HGNC:1749ENSG00000040731Q9Y6N8Cadherin-10gwas
KHDRBS3HGNC:18117ENSG00000131773O75525KH domain-containing, RNA-binding, signal transduction-associated protein 3gwas
KCNH7HGNC:18863ENSG00000184611Q9NS40Voltage-gated inwardly rectifying potassium channel KCNH7gwas
NEIL2HGNC:18956ENSG00000154328Q969S2Endonuclease 8-like 2gwas
THADAHGNC:19217ENSG00000115970Q6YHU6tRNA (32-2’-O)-methyltransferase regulator THADAgwas
PLGRKTHGNC:23633ENSG00000107020Q9HBL7Plasminogen receptor (KT)gwas
WWTR1HGNC:24042ENSG00000018408Q9GZV5WW domain-containing transcription regulator protein 1gwas
FAR2HGNC:25531ENSG00000064763Q96K12Fatty acyl-CoA reductase 2gwas
TRIML2HGNC:26378ENSG00000179046Q8N7C3Probable E3 ubiquitin-protein ligase TRIML2gwas
TRIML1HGNC:26698ENSG00000184108Q8N9V2Probable E3 ubiquitin-protein ligase TRIML1gwas
ARL14EPHGNC:26798ENSG00000152219Q8N8R7ARL14 effector proteingwas
KAZNHGNC:29173ENSG00000189337Q674X7Kazringwas
TTC28HGNC:29179ENSG00000100154Q96AY4Tetratricopeptide repeat protein 28gwas
DENND1AHGNC:29324ENSG00000119522Q8TEH3DENN domain-containing protein 1Agwas
GTF2A1LHGNC:30727ENSG00000242441Q9UNN4TFIIA-alpha and beta-like factorgwas
LINC02905HGNC:32200long intergenic non-protein coding RNA 2905gwas
SUMO1P1HGNC:33148ENSG00000241721G2XKQ0Small ubiquitin-related modifier 5gwas
ERBB2HGNC:3430ENSG00000141736P04626Receptor tyrosine-protein kinase erbB-2gwas
ERBB3HGNC:3431ENSG00000065361P21860Receptor tyrosine-protein kinase erbB-3gwas
ERBB4HGNC:3432ENSG00000178568Q15303Receptor tyrosine-protein kinase erbB-4gwas
FANCCHGNC:3584ENSG00000158169Q00597Fanconi anemia group C proteingwas
FDFT1HGNC:3629ENSG00000079459P37268Squalene synthasegwas
FSHBHGNC:3964ENSG00000131808P01225Follitropin subunit betagwas
FSHRHGNC:3969ENSG00000170820P23945Follicle-stimulating hormone receptorgwas
GABRA4HGNC:4078ENSG00000109158P48169Gamma-aminobutyric acid receptor subunit alpha-4gwas
GATA4HGNC:4173ENSG00000136574P43694Transcription factor GATA-4gwas
HMGA2HGNC:5009ENSG00000149948P52926High mobility group protein HMGI-Cgwas
KRR1HGNC:5176ENSG00000111615Q13601KRR1 small subunit processome component homologgwas
INSRHGNC:6091ENSG00000171105P06213Insulin receptorgwas
IRF1HGNC:6116ENSG00000125347P10914Interferon regulatory factor 1gwas
KCNA4HGNC:6222ENSG00000182255P22459Potassium voltage-gated channel subfamily A member 4gwas
LHCGRHGNC:6585ENSG00000138039P22888Lutropin-choriogonadotropic hormone receptorgwas
MAPRE1HGNC:6890ENSG00000101367Q15691Microtubule-associated protein RP/EB family member 1gwas
MYO10HGNC:7593ENSG00000145555Q9HD67Unconventional myosin-Xgwas
PRDM2HGNC:9347ENSG00000116731Q13029PR domain zinc finger protein 2gwas
RAB5BHGNC:9784ENSG00000111540P61020Ras-related protein Rab-5Bgwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
BMPR1BBone morphogenetic protein receptor type-1BOn ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
ZFP36L2mRNA decay activator protein ZFP36L2Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthes…
SOD2Superoxide dismutase [Mn], mitochondrialDestroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
SOX8Transcription factor SOX-8Transcription factor that may play a role in central nervous system, limb and facial development.
SSTR5Somatostatin receptor type 5Receptor for somatostatin 28 and to a lesser extent for somatostatin-14.
SUOXSulfite oxidase, mitochondrialCatalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
TOX3TOX high mobility group box family member 3Transcriptional coactivator of the p300/CBP-mediated transcription complex.
UNC5CNetrin receptor UNC5CReceptor for netrin required for axon guidance.
ZBTB16Zinc finger and BTB domain-containing protein 16Acts as a transcriptional repressor.
IKZF3Zinc finger protein AiolosTranscription factor that plays an important role in the regulation of lymphocyte differentiation.
FIGNFidgetinATP-dependent microtubule severing protein.
AOPEPAminopeptidase OAminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
LMF1Lipase maturation factor 1Involved in the maturation of specific proteins in the endoplasmic reticulum.
YAP1Transcriptional coactivator YAP1Transcriptional regulator with dual roles as a coactivator and corepressor.
CDH10Cadherin-10Cadherins are calcium-dependent cell adhesion proteins.
KHDRBS3KH domain-containing, RNA-binding, signal transduction-associated protein 3RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion.
KCNH7Voltage-gated inwardly rectifying potassium channel KCNH7Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.
NEIL2Endonuclease 8-like 2Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents.
THADAtRNA (32-2’-O)-methyltransferase regulator THADATogether with methyltransferase FTSJ1, methylates the 2’-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs.
PLGRKTPlasminogen receptor (KT)Receptor for plasminogen.
WWTR1WW domain-containing transcription regulator protein 1Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
FAR2Fatty acyl-CoA reductase 2Catalyzes the reduction of saturated but not unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols (FAls).
TRIML1Probable E3 ubiquitin-protein ligase TRIML1Probable E3 ubiquitin-protein ligase which plays an important role in blastocyst development.
ARL14EPARL14 effector proteinThrough its interaction with ARL14 and MYO1E, may connect MHC class II-containing cytoplasmic vesicles to the actin network and hence controls the movement of these vesicles along the actin cytoskeleton in dendritic cells.
KAZNKazrinComponent of the cornified envelope of keratinocytes.
TTC28Tetratricopeptide repeat protein 28During mitosis, may be involved in the condensation of spindle midzone microtubules, leading to the formation of midbody.
DENND1ADENN domain-containing protein 1AGuanine nucleotide exchange factor (GEF) regulating clathrin-mediated endocytosis through RAB35 activation.
GTF2A1LTFIIA-alpha and beta-like factorMay function as a testis specific transcription factor.
SUMO1P1Small ubiquitin-related modifier 5Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer.
ERBB2Receptor tyrosine-protein kinase erbB-2Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
ERBB3Receptor tyrosine-protein kinase erbB-3Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
ERBB4Receptor tyrosine-protein kinase erbB-4Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell prolife…
FANCCFanconi anemia group C proteinDNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
FDFT1Squalene synthaseCatalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene.
FSHBFollitropin subunit betaTogether with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer.
FSHRFollicle-stimulating hormone receptorG protein-coupled receptor for follitropin, the follicle-stimulating hormone.
GABRA4Gamma-aminobutyric acid receptor subunit alpha-4Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
GATA4Transcription factor GATA-4Transcriptional activator that binds to the consensus sequence 5’-AGATAG-3’ and plays a key role in cardiac development and function.
HMGA2High mobility group protein HMGI-CFunctions as a transcriptional regulator.
KRR1KRR1 small subunit processome component homologPart of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
INSRInsulin receptorReceptor tyrosine kinase which mediates the pleiotropic actions of insulin.
IRF1Interferon regulatory factor 1Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses.
KCNA4Potassium voltage-gated channel subfamily A member 4Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
LHCGRLutropin-choriogonadotropic hormone receptorReceptor for lutropin-choriogonadotropic hormone.
MAPRE1Microtubule-associated protein RP/EB family member 1Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton.
MYO10Unconventional myosin-XMyosins are actin-based motor molecules with ATPase activity.
PRDM2PR domain zinc finger protein 2S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates ‘Lys-9’ of histone H3.
RAB5BRas-related protein Rab-5BThe small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.
RAD50DNA repair protein RAD50Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
ASIC2Acid-sensing ion channel 2Forms pH-gated trimeric sodium channels that act as postsynaptic excitatory sensors in the nervous system.

Protein-family classification

Druggable: 15 · Difficult: 12 · Unknown: 25 · Druggable fraction: 0.29

Family distribution

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

FamilyGenesFoldFDR
Kinase52.7×0.350
Ion channel24.3×0.356
Transcription factor91.4×0.516
GPCR31.4×0.834
Scaffold/PPI31.0×0.897
Other/Unknown250.9×0.897
Protease10.7×0.897
Enzyme (other)30.7×0.897
Antibody/Immunoglobulin10.6×0.897

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BMPR1BKinaseyes2.7.10.2TGFB_receptor, Activin_recp, Prot_kinase_dom
ZFP36L2Transcription factornoZnf_CCCH, Tis11B_N, Znf_CCCH_sf
SOD2Enzyme (other)yes1.15.1.1Mn/Fe_SOD, Mn/Fe_SOD_N, Mn/Fe_SOD_C
SOX8Transcription factornoHMG_box_dom, Sox_N, HMG_box_dom_sf
SSTR5GPCRyesGPCR_Rhodpsn, Somatstn_rcpt, Somatstn_rcpt_5
SUOXEnzyme (other)yes1.8.3.1OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer
TOX3Other/UnknownnoHMG_box_dom, HMG_box_dom_sf, TOX_HMG-box_domain
UNC5CAntibody/ImmunoglobulinyesDeath_dom, TSP1_rpt, ZU5_dom
ZBTB16Transcription factornoBTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
IKZF3Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
FIGNOther/UnknownnoAAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
AOPEPProteaseyesPeptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
LMF1Other/UnknownnoLMF, LMF1/2_C, LMF1/2_N
YAP1Scaffold/PPInoWW_dom, WW_dom_sf, YAP1
CDH10Other/UnknownnoCadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
KHDRBS3Other/UnknownnoKH_dom, Sam68-YY, Qua1_dom
KCNH7Ion channelyesPAS, cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG
NEIL2Transcription factorno3.2.2.23Znf_DNA_glyclase/AP_lyase, Ribosomal_uS13-like_H2TH, FPG_cat
THADAOther/UnknownnoARM-type_fold, THADA/TRM732_DUF2428, tRNA_methyltransferase_THADA
PLGRKTOther/UnknownnoPlg-R(KT)
WWTR1Scaffold/PPInoWW_dom, WW_dom_sf, YAP1
FAR2Other/UnknownnoFAR_NAD-bd, FAR, FAR_C
TRIML2Transcription factornoZnf_B-box, B30.2/SPRY, SPRY_dom
TRIML1Transcription factornoZnf_RING, B30.2/SPRY, SPRY_dom
ARL14EPOther/UnknownnoARF7EP_C
KAZNOther/UnknownnoSAM, SAM/pointed_sf, Kazrin_SAM_rpt_1
TTC28Other/UnknownnoTPR-like_helical_dom_sf, TPR_rpt, CHAT_dom
DENND1AOther/UnknownnocDENN_dom, dDENN_dom, uDENN_dom
GTF2A1LOther/UnknownnoTFIIA_asu/bsu, TFIIA_b-brl
LINC02905Other/Unknownno
SUMO1P1Other/UnknownnoUbiquitin-like_dom, Rad60/SUMO-like_dom, Ubiquitin-like_domsf
ERBB2Kinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB3Kinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB4Kinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FANCCOther/UnknownnoFANCC
FDFT1Enzyme (other)yes2.5.1.21Squ/phyt_synthse, Squal_synth-like, Isoprenoid_synthase_dom_sf
FSHBOther/UnknownnoGonadotropin_bsu, Glyco_hormone_CN, Gonadotropin_bsu_CS
FSHRGPCRyesGPCR_Rhodpsn, LRRNT, Gphrmn_rcpt_fam
GABRA4Other/UnknownnoGABAAa_rcpt, GABBAa4_rcpt, GABAA/Glycine_rcpt
GATA4Transcription factornoZnf_GATA, GATA_N, Znf_NHR/GATA
HMGA2Other/UnknownnoHMGA, HMGI/Y_DNA-bd_CS, AT_hook_DNA-bd_motif
KRR1Other/UnknownnoKH_dom, rRNA_assembly_KRR1, KH_dom_type_1_sf
INSRKinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
IRF1Other/UnknownnoInterferon_reg_fact_DNA-bd_dom, IRF1/IRF2, Interferon_reg_fac_CS
KCNA4Ion channelyesBTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
LHCGRGPCRyesGPCR_Rhodpsn, Gphrmn_rcpt_fam, LSH_rcpt
MAPRE1Other/UnknownnoCH_dom, EB1_C, MAPRE
MYO10Scaffold/PPInoIQ_motif_EF-hand-BS, RA_dom, FERM_domain
PRDM2Transcription factornoSET_dom, PRDM2, Znf_C2H2_type
RAB5BOther/UnknownnoSmall_GTPase, Small_GTP-bd, P-loop_NTPase

Expression context

Cohort genes with no expression data: 1.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)50
unknown2

Top tissues across cohort

TissueCohort genes
male germ line stem cell (sensu Vertebrata) in testis9
buccal mucosa cell6
calcaneal tendon5
sural nerve5
right testis5
secondary oocyte5
cauda epididymis3
pancreatic ductal cell3
right uterine tube3
left testis3
primordial germ cell in gonad3
ganglionic eminence3
lower esophagus mucosa3
skin of hip2
upper leg skin2
inferior vagus X ganglion2
right atrium auricular region2
right lobe of liver2
colonic mucosa2
corpus callosum2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
BMPR1B239broadmarkercalcaneal tendon, bronchial epithelial cell, cauda epididymis
ZFP36L2303ubiquitousmarkerupper leg skin, skin of hip, mammary duct
SOD2ubiquitous
SOX8194broadmarkerinferior vagus X ganglion, lateral globus pallidus, subthalamic nucleus
SSTR575tissue_specificyestendon of biceps brachii, right atrium auricular region, cardiac atrium
SUOX267ubiquitousmarkerright lobe of liver, right adrenal gland, right adrenal gland cortex
TOX3220broadmarkermucosa of sigmoid colon, pancreatic ductal cell, colonic mucosa
UNC5C202broadmarkercorpus callosum, tibia, medial globus pallidus
ZBTB16281broadmarkerskin of hip, Brodmann (1909) area 23, tibialis anterior
IKZF3155broadmarkergranulocyte, lymph node, epithelium of nasopharynx
FIGN225ubiquitousmarkerbuccal mucosa cell, dorsal root ganglion, endothelial cell
AOPEP224ubiquitousmarkerapex of heart, right coronary artery, ascending aorta
LMF1276ubiquitousmarkerright uterine tube, C1 segment of cervical spinal cord, sural nerve
YAP1279ubiquitousmarkersaphenous vein, germinal epithelium of ovary, cauda epididymis
CDH10172broadmarkerBrodmann (1909) area 23, middle temporal gyrus, Brodmann (1909) area 46
KHDRBS3267ubiquitousmarkercortical plate, left testis, right testis
KCNH790tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, ventricular zone
NEIL2224ubiquitousmarkeroviduct epithelium, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis
THADA276ubiquitousmarkercalcaneal tendon, right uterine tube, right lobe of thyroid gland
PLGRKT242ubiquitousmarkerrectum, mucosa of transverse colon, colonic mucosa
WWTR1292ubiquitousmarkertibia, blood vessel layer, cauda epididymis
FAR2228ubiquitousmarkerupper leg skin, mucosa of transverse colon, bone marrow cell
TRIML2111tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right testis
TRIML122tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, left testis, right testis
ARL14EP248ubiquitousmarkersecondary oocyte, oocyte, calcaneal tendon
KAZN277ubiquitousmarkercerebellar vermis, inferior vagus X ganglion, esophagus squamous epithelium
TTC28278tissue_specificmarkerganglionic eminence, corpus epididymis, cortical plate
DENND1A213ubiquitousmarkermonocyte, leukocyte, bone marrow cell
GTF2A1L156tissue_specificyesleft testis, primordial germ cell in gonad, right testis
LINC02905

Protein interactions among cohort

Intra-cohort edges: 34.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ERBB29,659
YAP16,742
SOD26,580
GATA44,994
ERBB34,511
INSR4,446
MAPRE14,327
ERBB44,325
IRF14,076
KRR13,566

Intra-cohort edges

ABSources
AOPEPDENND1Astring_interaction
AOPEPFSHRstring_interaction
AOPEPINSRstring_interaction
AOPEPKRR1string_interaction
AOPEPLHCGRstring_interaction
AOPEPNEIL2string_interaction
AOPEPSUOXstring_interaction
AOPEPTHADAstring_interaction
AOPEPTOX3string_interaction
ARL14EPFSHBstring_interaction
ARL14EPPLGRKTstring_interaction
ARL14EPSUOXstring_interaction
ASIC2FAR2biogrid_interaction
CDH10GABRA4string_interaction
DENND1AFSHRstring_interaction
DENND1AGTF2A1Lstring_interaction
DENND1AKRR1string_interaction
DENND1ALHCGRstring_interaction
DENND1ASUOXstring_interaction
DENND1ATHADAstring_interaction
DENND1ATOX3string_interaction
ERBB2ERBB3biogrid_interaction, intact, string_interaction
ERBB2ERBB4intact, string_interaction
ERBB3ERBB4intact, string_interaction
ERBB4YAP1biogrid_interaction, string_interaction
FIGNKCNH7string_interaction
FSHBFSHRintact, string_interaction
FSHBLHCGRstring_interaction
GTF2A1LLHCGRstring_interaction
KRR1SUOXstring_interaction
KRR1TOX3string_interaction
LHCGRTHADAstring_interaction
PRDM2SOD2intact
SUOXTOX3string_interaction

Structural data

PDB: 32 · AlphaFold-only: 19 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
INSRP0621388
ERBB2P0462663
SOD2P0417948
YAP1P4693741
FDFT1P3726832
MAPRE1Q1569132
ERBB3P2186023
ERBB4Q1530314
WWTR1Q9GZV511
SSTR5P353467
MYO10Q9HD677
FANCCQ005976
FSHBP012256
RAD50Q928786
KHDRBS3O755255
FSHRP239455
GABRA4P481695
LHCGRP228884
ZFP36L2P479743
ZBTB16Q055163
GATA4P436943
THADAQ6YHU62
KRR1Q136012
PRDM2Q130292
BMPR1BO002381
SUOXP516871
KCNH7Q9NS401
ARL14EPQ8N8R71
DENND1AQ8TEH31
SUMO1P1G2XKQ01

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
FAR2Q96K1294.15
LMF1Q96S0690.49
PLGRKTQ9HBL789.60
TRIML2Q8N7C386.66
TRIML1Q8N9V286.29
AOPEPQ8N6M683.36
NEIL2Q969S281.95
UNC5CO9518578.72
CDH10Q9Y6N878.29
KAZNQ674X771.09
KCNA4P2245970.48
TTC28Q96AY469.05
IRF1P1091466.65
HMGA2P5292665.46
FIGNQ5HY9262.06
TOX3O1540560.22
SOX8P5707359.57
GTF2A1LQ9UNN453.77
IKZF3Q9UKT948.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 235. Enrichment computed across 52 evidence-associated genes (39 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 39 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Hormone ligand-binding receptors373.2×0.001FSHB, FSHR, LHCGR
ERBB2 Activates PTK6 Signaling362.8×0.001ERBB2, ERBB3, ERBB4
YAP1- and WWTR1 (TAZ)-stimulated gene expression358.6×0.001YAP1, WWTR1, GATA4
ERBB2 Regulates Cell Motility354.9×0.001ERBB2, ERBB3, ERBB4
PI3K events in ERBB2 signaling351.7×0.001ERBB2, ERBB3, ERBB4
SHC1 events in ERBB2 signaling336.6×0.002ERBB2, ERBB3, ERBB4
Signaling by ERBB2 TMD/JMD mutants336.6×0.002ERBB2, ERBB3, ERBB4
Signaling by ERBB2 KD Mutants332.5×0.003ERBB2, ERBB3, ERBB4
Downregulation of ERBB2 signaling329.3×0.004ERBB2, ERBB3, ERBB4
GRB7 events in ERBB2 signaling297.6×0.004ERBB2, ERBB3
Signaling by ERBB2326.6×0.004ERBB2, ERBB3, ERBB4
RUNX3 regulates YAP1-mediated transcription273.2×0.006YAP1, WWTR1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling49.9×0.012ERBB2, ERBB3, ERBB4, INSR
Downregulation of ERBB2:ERBB3 signaling241.8×0.017ERBB2, ERBB3
Physiological factors234.5×0.023WWTR1, GATA4
GRB2 events in ERBB2 signaling232.5×0.025ERBB2, ERBB4
Signaling by Hippo227.9×0.032YAP1, WWTR1
PIP3 activates AKT signaling46.8×0.035ERBB2, ERBB3, ERBB4, INSR
RUNX2 regulates osteoblast differentiation223.4×0.040YAP1, WWTR1
Constitutive Signaling by Aberrant PI3K in Cancer39.8×0.041ERBB2, ERBB3, ERBB4
EGR2 and SOX10-mediated initiation of Schwann cell myelination218.9×0.056YAP1, WWTR1
Nuclear signaling by ERBB4217.8×0.057YAP1, ERBB4
Regulation of PD-L1(CD274) transcription38.4×0.057YAP1, WWTR1, IRF1
PLCG1 events in ERBB2 signaling173.2×0.084ERBB2
Wax biosynthesis173.2×0.084FAR2
Drug-mediated inhibition of ERBB2 signaling173.2×0.084ERBB2
Resistance of ERBB2 KD mutants to trastuzumab173.2×0.084ERBB2
Resistance of ERBB2 KD mutants to sapitinib173.2×0.084ERBB2
Resistance of ERBB2 KD mutants to tesevatinib173.2×0.084ERBB2
Resistance of ERBB2 KD mutants to neratinib173.2×0.084ERBB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 50 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
cardiac muscle tissue regeneration3252.8×6e-05YAP1, ERBB4, GATA4
male gonad development618.7×2e-04SOX8, FSHR, GATA4, HMGA2, INSR, LHCGR
follicle-stimulating hormone signaling pathway2224.7×0.004FSHB, FSHR
negative regulation of fat cell differentiation425.0×0.004ZFP36L2, SOD2, YAP1, WWTR1
positive regulation of epithelial cell proliferation419.5×0.006YAP1, ERBB2, ERBB3, ERBB4
wound healing418.2×0.006YAP1, ERBB2, ERBB3, GATA4
regulation of metanephric nephron tubule epithelial cell differentiation2134.8×0.007YAP1, WWTR1
ERBB2-ERBB4 signaling pathway2112.3×0.008ERBB2, ERBB4
Sertoli cell proliferation2112.3×0.008FSHB, FSHR
heart process284.3×0.012YAP1, WWTR1
mesenchymal cell differentiation284.3×0.012WWTR1, HMGA2
ERBB2-ERBB3 signaling pathway267.4×0.017ERBB2, ERBB3
positive regulation of DNA-templated transcription84.5×0.017SOX8, ZBTB16, YAP1, ERBB4, GATA4, HMGA2, INSR, IRF1
regulation of osteoclast differentiation261.3×0.019FSHB, FSHR
cellular response to growth factor stimulus319.1×0.019BMPR1B, ERBB2, INSR
cellular response to epidermal growth factor stimulus319.1×0.019ZFP36L2, ERBB2, ERBB4
endocardial cushion development256.2×0.019ERBB3, GATA4
regulation of B cell differentiation251.9×0.020ZFP36L2, IKZF3
cell fate commitment317.7×0.020SOX8, ERBB4, GATA4
Sertoli cell development244.9×0.024SOX8, FSHR
hemopoiesis316.1×0.024ZFP36L2, SOD2, ZBTB16
Schwann cell development242.1×0.026ERBB2, ERBB3
epidermal growth factor receptor signaling pathway314.9×0.026ERBB2, ERBB3, ERBB4
somatic stem cell population maintenance314.9×0.026ZFP36L2, YAP1, HMGA2
positive regulation of cartilage development237.5×0.028BMPR1B, ZBTB16
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway237.5×0.028SOD2, GATA4
negative regulation of stem cell differentiation233.7×0.029ZFP36L2, YAP1
female gamete generation232.1×0.029FSHB, FSHR
positive regulation of chondrocyte differentiation232.1×0.029BMPR1B, ZBTB16
uterus development232.1×0.029FSHR, LHCGR

Therapeutics

Drugs indicated for this disease

0 approved, 17 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
ArgininePhase 3 (in late-stage trials)
CalciumPhase 3 (in late-stage trials)
CholecalciferolPhase 3 (in late-stage trials)
ChromiumPhase 3 (in late-stage trials)
CinnamonPhase 3 (in late-stage trials)
DapagliflozinPhase 3 (in late-stage trials)
DesogestrelPhase 3 (in late-stage trials)
DextrosePhase 3 (in late-stage trials)
DrospirenonePhase 3 (in late-stage trials)
Ethinyl EstradiolPhase 3 (in late-stage trials)
Gonadotropin, ChorionicPhase 3 (in late-stage trials)
LetrozolePhase 3 (in late-stage trials)
LiraglutidePhase 3 (in late-stage trials)
MenotropinsPhase 3 (in late-stage trials)
MetforminPhase 3 (in late-stage trials)
RaloxifenePhase 3 (in late-stage trials)
SimvastatinPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcarnitine, Acetylcysteine, Anakinra, Artenimol, Cabergoline, Chiglitazar, Choriogonadotropin Alfa, Cyproterone Acetate, Elagolix, Empagliflozin, Ergocalciferol, Exenatide, Flutamide, Follitropin, Levocarnitine, Orlistat, Pioglitazone, Progesterone, Resveratrol, Semaglutide, Sitagliptin, Spironolactone, Ubidecarenone, Vitamin E.

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 9 · Phased (≥1): 10 · Undrugged: 42

Druggability breadth: 24 of 52 evidence-associated genes (46%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

SymbolExample approved molecule
BMPR1BMOMELOTINIB
SSTR5LANREOTIDE
IKZF3POMALIDOMIDE
ERBB2CLOTRIMAZOLE
ERBB3MOBOCERTINIB
ERBB4MOBOCERTINIB
FDFT1AMIODARONE
GABRA4ENZALUTAMIDE
INSRFEDRATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
ERBB2834
ERBB4474
INSR364
BMPR1B284
ERBB3234
GABRA4184
SSTR5114
IKZF354
FDFT134
RAD5012

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
MOMELOTINIB4BMPR1B
FEDRATINIB4BMPR1B, ERBB4, INSR
AXITINIB4BMPR1B
RUXOLITINIB4BMPR1B
VANDETANIB4BMPR1B, ERBB2, ERBB3, ERBB4
GILTERITINIB4BMPR1B
PAZOPANIB4BMPR1B
SUNITINIB4BMPR1B, INSR
DASATINIB4BMPR1B, ERBB2, ERBB3, ERBB4
QUIZARTINIB4BMPR1B
CRIZOTINIB4BMPR1B, INSR
LANREOTIDE4SSTR5
OCTREOTIDE4SSTR5
GALLIUM OXODOTREOTIDE4SSTR5
ASTEMIZOLE4ERBB2, SSTR5
PASIREOTIDE4SSTR5
LOPERAMIDE4SSTR5
POMALIDOMIDE4IKZF3
LENALIDOMIDE4IKZF3
THALIDOMIDE4IKZF3
CLOTRIMAZOLE4ERBB2
ERLOTINIB HYDROCHLORIDE4ERBB2
PONATINIB4ERBB2
AFATINIB4ERBB2, ERBB3, ERBB4
LAPATINIB DITOSYLATE4ERBB2
SORAFENIB4ERBB2, INSR
NERATINIB4ERBB2, ERBB3, ERBB4, INSR
IBRUTINIB4ERBB2, ERBB4
AFATINIB DIMALEATE4ERBB2, ERBB4
CABOZANTINIB4ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

SymbolAssaysType breakdown
ERBB21,221Binding:1136, Functional:79, ADMET:6
INSR954Binding:900, Functional:49, ADMET:4, Toxicity:1
ERBB4591Binding:579, ADMET:8, Functional:4
GABRA4273Binding:233, Functional:36, Toxicity:3, ADMET:1
ERBB3169Binding:169
BMPR1B166Binding:164, ADMET:2
SSTR5151Binding:123, Functional:24, ADMET:4
YAP1135Binding:135
IKZF3101Binding:100, Functional:1
LHCGR54Binding:35, Functional:18, ADMET:1
FSHR43Functional:26, Binding:17
FDFT140Binding:40
KCNA430Binding:26, ADMET:2, Toxicity:1, Functional:1
KCNH721Binding:20, Toxicity:1
RAD507Binding:7
GATA45Binding:5
ZBTB163Binding:3
SOD22Binding:2
WWTR12Binding:2
AOPEP1ADMET:1
NEIL21Functional:1
MAPRE11Binding:1
PRDM21Binding:1
RAB5B1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BMPR1B2.7.10.2non-specific protein-tyrosine kinase
SOD21.15.1.1superoxide dismutase
SUOX1.8.3.1sulfite oxidase
NEIL23.2.2.23DNA-formamidopyrimidine glycosylase
ERBB22.7.10.1receptor protein-tyrosine kinase
ERBB32.7.10.1receptor protein-tyrosine kinase
ERBB42.7.10.1receptor protein-tyrosine kinase
FDFT12.5.1.21squalene synthase
INSR2.7.10.1receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BMPR1B166
SSTR5151
IKZF3101
YAP1135
ERBB21,221
ERBB3169
ERBB4591
GABRA4273
INSR954

Pharmacogenomics

Cohort genes with a PharmGKB record: 52; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

CompoundMax phaseCohort target (bioactivity)
MOMELOTINIB4BMPR1B
FEDRATINIB4BMPR1B, ERBB4, INSR
AXITINIB4BMPR1B
RUXOLITINIB4BMPR1B
VANDETANIB4BMPR1B, ERBB2, ERBB3, ERBB4
GILTERITINIB4BMPR1B
PAZOPANIB4BMPR1B
SUNITINIB4BMPR1B, INSR
DASATINIB4BMPR1B, ERBB2, ERBB3, ERBB4
QUIZARTINIB4BMPR1B
CRIZOTINIB4BMPR1B, INSR
LANREOTIDE4SSTR5
OCTREOTIDE4SSTR5
GALLIUM OXODOTREOTIDE4SSTR5
ASTEMIZOLE4ERBB2, SSTR5
PASIREOTIDE4SSTR5
LOPERAMIDE4SSTR5
POMALIDOMIDE4IKZF3
LENALIDOMIDE4IKZF3
THALIDOMIDE4IKZF3
CLOTRIMAZOLE4ERBB2
ERLOTINIB HYDROCHLORIDE4ERBB2
PONATINIB4ERBB2
AFATINIB4ERBB2, ERBB3, ERBB4
LAPATINIB DITOSYLATE4ERBB2
SORAFENIB4ERBB2, INSR
NERATINIB4ERBB2, ERBB3, ERBB4, INSR
IBRUTINIB4ERBB2, ERBB4
AFATINIB DIMALEATE4ERBB2, ERBB4
CABOZANTINIB4ERBB2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)9BMPR1B, SSTR5, IKZF3, ERBB2, ERBB3, ERBB4, FDFT1, GABRA4, INSR
BPhased (≥1) drug, not yet approved1RAD50
CDruggable family + PDB, no drug5SOD2, SUOX, KCNH7, FSHR, LHCGR
DDruggable family + AlphaFold only, no drug3UNC5C, AOPEP, KCNA4
EDifficult family or no structure, no drug34ZFP36L2, SOX8, TOX3, ZBTB16, FIGN, LMF1, YAP1, CDH10, KHDRBS3, NEIL2 (+24 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
YAP1135
ZFP36L20
SOD22
SOX80
SUOX0
TOX30
UNC5C0
ZBTB163
FIGN0
AOPEP1
LMF10
CDH100
KHDRBS30
KCNH721
NEIL21
THADA0
PLGRKT0
WWTR12
FAR20
TRIML20
TRIML10
ARL14EP0
KAZN0
TTC280
DENND1A0
GTF2A1L0
LINC029050
SUMO1P10
FANCC0
FSHB0

Clinical trials & evidence

Clinical trials

Clinical trials: 830.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified546
PHASE4116
PHASE352
PHASE239
EARLY_PHASE128
PHASE121
PHASE2/PHASE315
PHASE1/PHASE213

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05206448PHASE4ACTIVE_NOT_RECRUITINGRandomized Controlled Trial of Combined Letrozole and Clomid (CLC II) Versus Letrozole Alone for Women With Anovulation
NCT05680805PHASE4ACTIVE_NOT_RECRUITINGMetabolic Responses of Metformin and Genetic Polymorphisms of SLC22A1 Gene in PCOS
NCT06742710PHASE4RECRUITINGLiraglutide Treatment in Obese Infertile PCOS Women
NCT06823830PHASE4ACTIVE_NOT_RECRUITINGClinical、metabolomics and the Study of Intestinal Flora of Jinfeng Pills in the Treatment of Polycystic Ovary Syndrome
NCT07326111PHASE4RECRUITINGA Clincial Study Testing Tirzepatide on Reproductive Function and Metabolic Health in Women With PCOS Who Are Overweight or Obese
NCT00145340PHASE4COMPLETEDPioglitazone Treatment in Polycystic Ovary Syndrome
NCT00159575PHASE4TERMINATEDMetformin in Assisted Reproduction-MET-AR-study
NCT00203996PHASE4TERMINATEDPolycystic Ovary Syndrome (PCOS) and Sleep Apnea
NCT00378729PHASE4UNKNOWNSurgical Ovarian Drilling Versus Hormonal Treatment for Infertility Associated to PolyCystic Ovaries Syndrome (PCOS)
NCT00417144PHASE4UNKNOWNComparison Between GnRH Agonist and GnRH Antagonist Protocols of Ovarian Stimulation in PCOS Patients
NCT00428311PHASE4COMPLETEDEffects of Metformin vs Oral Contraceptives on CV Risk Markers in PCOS
NCT00437333PHASE4COMPLETEDMetformin Suspension and Insulin Sensitivity
NCT00451568PHASE4COMPLETEDMetformin and Oral Contraceptives in PCOS
NCT00463112PHASE4COMPLETEDEffect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00471523PHASE4COMPLETEDTreatment of Anovulatory Infertility in PCOS Patients
NCT00473538PHASE4COMPLETEDStructured Exercise Training Program Versus Hypocaloric Hyperproteic Diet in Obese Anovulatory Infertile Patients With PCOS
NCT00501787PHASE4WITHDRAWNMetformin Administration in Infertile Anovulatory PCOS Patients
NCT00501839PHASE4WITHDRAWNClomiphene Citrate in Infertile PCOS Patients
NCT00501904PHASE4UNKNOWNMetformin in Infertile PCOS Patients
NCT00502229PHASE4WITHDRAWNTherapy for Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin
NCT00502281PHASE4SUSPENDEDControlled Ovarian Stimulation Followed by Timed Intercourse or Intrauterine Insemination in Infertile PCOS Patients
NCT00558077PHASE4COMPLETEDSecond-Line Treatments for Anovulatory Infertility in PCOS Patients
NCT00593294PHASE4COMPLETEDOral Contraceptive and Cardiovascular Risk in PCOS
NCT00620529PHASE4COMPLETEDThe Effects of Fish Oils on Blood Pressure, Heart Rate Variability and Liver Fat in the Polycystic Ovary Syndrome
NCT00640224PHASE4COMPLETEDInsulin Resistance, Polycystic Ovary Syndrome, and Bone Research Study
NCT00679679PHASE4COMPLETEDMetformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome
NCT00682890PHASE4TERMINATEDCombination Metformin and Oral Contraception for Polycystic Ovary Syndrome (PCOS)
NCT00703092PHASE4TERMINATEDPilot Study:Role of Dietary Fiber in PCOS Anovulation
NCT00795808PHASE4COMPLETEDPCOSMIC Trial - PolyCystic Ovary Syndrome, Metformin for Infertility With Clomiphene
NCT00883259PHASE4UNKNOWNMetformin and Gestational Diabetes in High-risk Patients: a RCTs
NCT00953355PHASE4COMPLETEDMetformin and Folate Supplementation in Polycystic Ovary Syndrome (PCOS) Patients
NCT01004068PHASE4COMPLETEDShort-term Structured Exercise Training Program Plus Diet Intervention in Patients With Polycystic Ovary Syndrome (PCOS)
NCT01021579PHASE4COMPLETEDEffects of Metformin Plus Simvastatin on Polycystic Ovarian Syndrome (PCOS): A Prospective, Randomized, Double-Blind, Placebo-Controlled Study
NCT01115140PHASE4COMPLETEDMetformin and Folate in Pregnant Polycystic Ovary Syndrome(PCOS) Women
NCT01118598PHASE4COMPLETEDEffect of Nicotinic Acid on Cardiovascular Risks Indices in Polycystic Ovary Syndrome
NCT01208740PHASE4TERMINATEDMetformin in Patients With PCOS and Predictors of Poor Ovarian Response Ongoing In-vitro Fertilization
NCT01233206PHASE4COMPLETEDMetformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles
NCT01360996PHASE4COMPLETEDLow Dose OC Therapy in Women With Polycystic Ovary Syndrome (PCOS): Impact of BMI on Hyperandrogenism
NCT01365936PHASE4COMPLETEDhMG or Recombinant FSH on OHSS Prevention in PCOS Patients Undergoing IVF
NCT01366391PHASE4UNKNOWNTherapeutic Monitoring of Metformin in Women With Polycystic Ovary Syndrome

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
CLOMIPHENE462
METFORMIN418
BERBERINE412
CETRORELIX410
PIOGLITAZONE49
LIRAGLUTIDE47
FLUTAMIDE46
LEVOCARNITINE46
FOLIC ACID45
LETROZOLE45
DROSPIRENONE44
ESTRADIOL VALERATE44
EXENATIDE44
GONADORELIN ACETATE44
ACARBOSE43
ARTENIMOL43
ERGOCALCIFEROL43
SITAGLIPTIN43
TRIPTORELIN43
CABERGOLINE42
CORTICOTROPIN42
COSYNTROPIN42
ETHINYL ESTRADIOL42
FISH OIL42
HYDROCORTISONE42
LEUPROLIDE42
LEUPROLIDE ACETATE42
ORLISTAT42
ROFLUMILAST42
SEMAGLUTIDE42