Kallmann syndrome

Summary

Kallmann syndrome (MONDO:0018800) is a disease (an umbrella term covering 18 Mondo subtypes) caused by TCF12 (GenCC Strong), with 28 cohort genes and 17 clinical trials. The dominant Reactome pathway is FGFR1c ligand binding and activation (4 cohort genes). Top therapeutic interventions include gonadorelin acetate, gonadotropin, chorionic, and anastrozole.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: TCF12 (GenCC Strong)
• Umbrella term: 18 Mondo subtypes
• Cohort genes: 28
• ClinVar variants: 9
• Phenotypes (HPO): 44
• Clinical trials: 17

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	3.75	Europe	Validated
Annual incidence	1-9 / 100 000	5	France	Validated
Annual incidence	1-9 / 100 000	2.1	Finland	Validated
Annual incidence	1-9 / 1 000 000	0.6	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0000044	Hypogonadotropic hypogonadism	Very frequent (80-99%)
HP:0000054	Micropenis	Very frequent (80-99%)
HP:0000144	Decreased fertility	Very frequent (80-99%)
HP:0000458	Anosmia	Very frequent (80-99%)
HP:0000823	Delayed puberty	Very frequent (80-99%)
HP:0000830	Anterior hypopituitarism	Very frequent (80-99%)
HP:0003164	Hypothalamic gonadotropin-releasing hormone (GNRH) deficiency	Very frequent (80-99%)
HP:0004409	Hyposmia	Very frequent (80-99%)
HP:0008734	Decreased testicular size	Very frequent (80-99%)
HP:0008736	Hypoplasia of penis	Very frequent (80-99%)
HP:0100639	Erectile dysfunction	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0001608	Abnormality of the voice	Frequent (30-79%)
HP:0003187	Breast hypoplasia	Frequent (30-79%)
HP:0004349	Reduced bone mineral density	Frequent (30-79%)
HP:0000008	Abnormal morphology of female internal genitalia	Occasional (5-29%)
HP:0000104	Renal agenesis	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000551	Color vision defect	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000771	Gynecomastia	Occasional (5-29%)
HP:0000786	Primary amenorrhea	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001324	Muscle weakness	Occasional (5-29%)
HP:0001335	Bimanual synkinesia	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001513	Obesity	Occasional (5-29%)
HP:0001761	Pes cavus	Occasional (5-29%)
HP:0001763	Pes planus	Occasional (5-29%)
HP:0002652	Skeletal dysplasia	Occasional (5-29%)
HP:0002750	Delayed skeletal maturation	Occasional (5-29%)
HP:0002757	Recurrent fractures	Occasional (5-29%)
HP:0008064	Ichthyosis	Occasional (5-29%)
HP:0009804	Tooth agenesis	Occasional (5-29%)
HP:0010550	Paraplegia	Occasional (5-29%)
HP:0030016	Dyspareunia	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Kallmann syndrome
Mondo ID	MONDO:0018800
MeSH	D017436
Orphanet	478
DOID	DOID:3614
NCIT	C75479
SNOMED CT	93559003
UMLS	C0162809
MedGen	102469
GARD	0010771
MedDRA	10053142
NORD	1319
Is cancer (heuristic)	no

Also known as: congenital hypogonadotropic hypogonadism with anosmia · hypogonadotropic hypogonadism with anosmia · Olfacto-genital pathological sequence

Data availability: 9 ClinVar variants · 25 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 18 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Kallmann 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, polycystic ovary 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, 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

Subtypes (18): hypogonadotropic hypogonadism 2 with or without anosmia, hypogonadotropic hypogonadism 3 with or without anosmia, hypogonadotropic hypogonadism 1 with or without anosmia, hypogonadotropic hypogonadism 4 with or without anosmia, hypogonadotropic hypogonadism 5 with or without anosmia, hypogonadotropic hypogonadism 6 with or without anosmia, hypogonadotropic hypogonadism 8 with or without anosmia, hypogonadotropic hypogonadism 9 with or without anosmia, hypogonadotropic hypogonadism 11 with or without anosmia, hypogonadotropic hypogonadism 14 with or without anosmia, hypogonadotropic hypogonadism 15 with or without anosmia, hypogonadotropic hypogonadism 16 with or without anosmia, hypogonadotropic hypogonadism 17 with or without anosmia, hypogonadotropic hypogonadism 18 with or without anosmia, hypogonadotropic hypogonadism 19 with or without anosmia, hypogonadotropic hypogonadism 20 with or without anosmia, hypogonadotropic hypogonadism 21 with or without anosmia, hypogonadotropic hypogonadism 22 with or without anosmia

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 4 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
635961	NC_000008.11:g.38463238_38470748del	FGFR1	Pathogenic	criteria provided, single submitter
1172662	NM_001166114.2(PNPLA6):c.3885dup (p.Ser1296fs)	PNPLA6	Pathogenic	criteria provided, single submitter
813829	NM_006941.4(SOX10):c.125_132del (p.Leu42fs)	POLR2F	Pathogenic	criteria provided, single submitter
871833	NM_006941.4(SOX10):c.89C>A (p.Ser30Ter)	POLR2F	Pathogenic	criteria provided, multiple submitters, no conflicts
3451	NM_144773.4(PROKR2):c.254G>A (p.Arg85His)	PROKR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3773789	NM_006941.4(SOX10):c.532C>T (p.Arg178Trp)	POLR2F	Uncertain significance	criteria provided, single submitter
3780663	NM_001127496.3(SPRY4):c.524C>T (p.Thr175Met)	SPRY4	Uncertain significance	criteria provided, multiple submitters, no conflicts
638187	NM_001035235.4(SRA1):c.341G>A (p.Arg114His)	SRA1	Uncertain significance	no assertion criteria provided
1805150	NM_207037.2(TCF12):c.20dup (p.Met8fs)	TCF12	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 201 · Orphanet: 78 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
TCF12	Strong	Autosomal dominant	Kallmann syndrome	11
ANOS1	Supportive	Autosomal dominant	Kallmann syndrome	4
CCDC141	Supportive	Autosomal dominant	Kallmann syndrome	2
CHD7	Supportive	Autosomal dominant	Kallmann syndrome	8
DCC	Supportive	Autosomal dominant	Kallmann syndrome	12
DUSP6	Supportive	Autosomal dominant	Kallmann syndrome	5
FEZF1	Supportive	Autosomal dominant	Kallmann syndrome	5
FGF17	Supportive	Autosomal dominant	Kallmann syndrome	4
FGF8	Supportive	Autosomal dominant	Kallmann syndrome	9
FGFR1	Supportive	Autosomal dominant	Kallmann syndrome	36
FLRT3	Supportive	Autosomal dominant	Kallmann syndrome	4
HESX1	Supportive	Autosomal dominant	Kallmann syndrome	12
HS6ST1	Supportive	Autosomal dominant	Kallmann syndrome	5
IL17RD	Supportive	Autosomal dominant	Kallmann syndrome	3
NDNF	Supportive	Autosomal dominant	Kallmann syndrome	3
PHIP	Supportive	Autosomal dominant	Kallmann syndrome	15
PROK2	Supportive	Autosomal dominant	Kallmann syndrome	7
PROKR2	Supportive	Autosomal dominant	Kallmann syndrome	8
SEMA3A	Supportive	Autosomal dominant	Kallmann syndrome	7
SOX10	Supportive	Autosomal dominant	Kallmann syndrome	15
SPRY4	Supportive	Autosomal dominant	Kallmann syndrome	5
TACR3	Supportive	Autosomal dominant	Kallmann syndrome	5
WDR11	Supportive	Autosomal dominant	Kallmann syndrome	10
AXL	Limited	Autosomal dominant	Kallmann syndrome
SEMA3E	Limited	Autosomal dominant	Kallmann syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCF12	Orphanet:209916	Extraskeletal myxoid chondrosarcoma
TCF12	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
SPRY4	Orphanet:363494	Non-seminomatous germ cell tumor of testis
SPRY4	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
SPRY4	Orphanet:478	Kallmann syndrome
PROKR2	Orphanet:3157	Septo-optic dysplasia spectrum
PROKR2	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
PROKR2	Orphanet:478	Kallmann syndrome
PROKR2	Orphanet:95496	Pituitary stalk interruption syndrome
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
SEMA3A	Orphanet:130	Brugada syndrome
SEMA3A	Orphanet:478	Kallmann syndrome
SEMA3E	Orphanet:138	CHARGE syndrome
SOX10	Orphanet:163746	Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease
SOX10	Orphanet:478	Kallmann syndrome
SOX10	Orphanet:895	Waardenburg syndrome type 2
SOX10	Orphanet:897	Waardenburg-Shah syndrome
TACR3	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
TACR3	Orphanet:478	Kallmann syndrome
WDR11	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
WDR11	Orphanet:478	Kallmann syndrome
WDR11	Orphanet:95496	Pituitary stalk interruption syndrome
PHIP	Orphanet:589905	PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome
IL17RD	Orphanet:478	Kallmann syndrome
PROK2	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
PROK2	Orphanet:478	Kallmann syndrome
CHD7	Orphanet:138	CHARGE syndrome
CHD7	Orphanet:39041	Omenn syndrome
CHD7	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
CHD7	Orphanet:478	Kallmann syndrome
FEZF1	Orphanet:478	Kallmann syndrome
NDNF	Orphanet:478	Kallmann syndrome
CCDC141	Orphanet:478	Kallmann syndrome
DCC	Orphanet:238722	Familial congenital mirror movements

Cohort genes → proteins

28 cohort genes, 28 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	28

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCF12	HGNC:11623	ENSG00000140262	Q99081	Transcription factor 12	gencc,clinvar
SPRY4	HGNC:15533	ENSG00000187678	Q9C004	Protein sprouty homolog 4	gencc,clinvar
PROKR2	HGNC:15836	ENSG00000101292	Q8NFJ6	Prokineticin receptor 2	gencc,clinvar
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	gencc,clinvar
SEMA3A	HGNC:10723	ENSG00000075213	Q14563	Semaphorin-3A	gencc
SEMA3E	HGNC:10727	ENSG00000170381	O15041	Semaphorin-3E	gencc
SOX10	HGNC:11190	ENSG00000100146	P56693	Transcription factor SOX-10	gencc
TACR3	HGNC:11528	ENSG00000169836	P29371	Neuromedin-K receptor	gencc
WDR11	HGNC:13831	ENSG00000120008	Q9BZH6	WD repeat-containing protein 11	gencc
PHIP	HGNC:15673	ENSG00000146247	Q8WWQ0	PH-interacting protein	gencc
IL17RD	HGNC:17616	ENSG00000144730	Q8NFM7	Interleukin-17 receptor D	gencc
PROK2	HGNC:18455	ENSG00000163421	Q9HC23	Prokineticin-2	gencc
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	gencc
FEZF1	HGNC:22788	ENSG00000128610	A0PJY2	Fez family zinc finger protein 1	gencc
NDNF	HGNC:26256	ENSG00000173376	Q8TB73	Protein NDNF	gencc
CCDC141	HGNC:26821	ENSG00000163492	Q6ZP82	Coiled-coil domain-containing protein 141	gencc
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	gencc
DUSP6	HGNC:3072	ENSG00000139318	Q16828	Dual specificity protein phosphatase 6	gencc
FGF17	HGNC:3673	ENSG00000158815	O60258	Fibroblast growth factor 17	gencc
FGF8	HGNC:3686	ENSG00000107831	P55075	Fibroblast growth factor 8	gencc
FLRT3	HGNC:3762	ENSG00000125848	Q9NZU0	Leucine-rich repeat transmembrane protein FLRT3	gencc
HESX1	HGNC:4877	ENSG00000163666	Q9UBX0	Homeobox expressed in ES cells 1	gencc
HS6ST1	HGNC:5201	ENSG00000136720	O60243	Heparan-sulfate 6-O-sulfotransferase 1	gencc
ANOS1	HGNC:6211	ENSG00000011201	P23352	Anosmin-1	gencc
AXL	HGNC:905	ENSG00000167601	P30530	Tyrosine-protein kinase receptor UFO	gencc
SRA1	HGNC:11281	ENSG00000213523	Q9HD15	Steroid receptor RNA activator 1	clinvar
PNPLA6	HGNC:16268	ENSG00000032444	Q8IY17	Patatin-like phospholipase domain-containing protein 6	clinvar
POLR2F	HGNC:9193	ENSG00000100142	P61218	DNA-directed RNA polymerases I, II, and III subunit RPABC2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCF12	Transcription factor 12	Transcriptional regulator.
SPRY4	Protein sprouty homolog 4	Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras.
PROKR2	Prokineticin receptor 2	Receptor for prokineticin 2.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
SEMA3A	Semaphorin-3A	Involved in the development of the olfactory system and in neuronal control of puberty.
SEMA3E	Semaphorin-3E	Plays an important role in signaling via the cell surface receptor PLXND1.
SOX10	Transcription factor SOX-10	Transcription factor that plays a central role in developing and mature glia.
TACR3	Neuromedin-K receptor	Receptor for the tachykinin neuromedin-K (neurokinin B), also able to bind and respond to tachynins substance K/neurokinin A and substance P.
WDR11	WD repeat-containing protein 11	Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis.
PHIP	PH-interacting protein	Probable regulator of the insulin and insulin-like growth factor signaling pathways.
IL17RD	Interleukin-17 receptor D	Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation.
PROK2	Prokineticin-2	May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm.
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
FEZF1	Fez family zinc finger protein 1	Transcription repressor.
NDNF	Protein NDNF	Secretory protein that plays a role in various cellular processes.
CCDC141	Coiled-coil domain-containing protein 141	Plays a critical role in cortical radial and GnRH neurons migration during brain development.
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
DUSP6	Dual specificity protein phosphatase 6	Dual specificity protein phosphatase, which mediates dephosphorylation and inactivation of MAP kinases.
FGF17	Fibroblast growth factor 17	Plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain.
FGF8	Fibroblast growth factor 8	Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration.
FLRT3	Leucine-rich repeat transmembrane protein FLRT3	Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners.
HESX1	Homeobox expressed in ES cells 1	Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland.
HS6ST1	Heparan-sulfate 6-O-sulfotransferase 1	6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.
ANOS1	Anosmin-1	Has a dual branch-promoting and guidance activity, which may play an important role in the patterning of mitral and tufted cell collaterals to the olfactory cortex.
AXL	Tyrosine-protein kinase receptor UFO	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migratio…
SRA1	Steroid receptor RNA activator 1	Functional RNA which acts as a transcriptional coactivator that selectively enhances steroid receptor-mediated transactivation ligand-independently through a mechanism involving the modulating N-terminal domain (AF-1) of steroid receptors.
PNPLA6	Patatin-like phospholipase domain-containing protein 6	Phospholipase B that deacylates intracellular phosphatidylcholine (PtdCho), generating glycerophosphocholine (GroPtdCho).
POLR2F	DNA-directed RNA polymerases I, II, and III subunit RPABC2	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.

Protein-family classification

Druggable: 12 · Difficult: 6 · Unknown: 10 · Druggable fraction: 0.43

Family distribution

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

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	7	7.3×	2e-04
Phosphatase	1	3.0×	0.569
Kinase	2	2.0×	0.569
GPCR	2	1.7×	0.569
Scaffold/PPI	2	1.2×	0.569
Transcription factor	4	1.2×	0.569
Other/Unknown	10	0.6×	0.990

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCF12	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
SPRY4	Other/Unknown	no		Sprouty, Sprouty_domain
PROKR2	GPCR	yes		GPCR_Rhodpsn, NPY_rcpt, GPCR_Rhodpsn_7TM
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
SEMA3A	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
SEMA3E	Antibody/Immunoglobulin	yes		Semap_dom, Ig-like_dom, Immunoglobulin_dom
SOX10	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf
TACR3	GPCR	yes		GPCR_Rhodpsn, NK3_rcpt, Neurokn_rcpt
WDR11	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
PHIP	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
IL17RD	Other/Unknown	no		SEFIR_dom, IL17R_D_N, Toll_tir_struct_dom_sf
PROK2	Other/Unknown	no		Prokineticin, Prokineticin_domain
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
FEZF1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
NDNF	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, NDNF
CCDC141	Antibody/Immunoglobulin	yes		Spectrin_repeat, Ig_sub2, Ig_sub
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
DUSP6	Phosphatase	yes	3.1.3.16	Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Rhodanese-like_dom
FGF17	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
FGF8	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
FLRT3	Antibody/Immunoglobulin	yes		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
HESX1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
HS6ST1	Other/Unknown	no		Sulfotransferase, Heparan_SO4-6-sulfoTrfase, P-loop_NTPase
ANOS1	Antibody/Immunoglobulin	yes		FN3_dom, WAP_dom, Ig-like_fold
AXL	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub
SRA1	Other/Unknown	no		SRA1/Sec31, Steroid_recept_RNA_1
PNPLA6	Other/Unknown	no		cNMP-bd_dom, LysoPLipase_patatin_CS, PNPLA_dom
POLR2F	Other/Unknown	no		Pol_omega/Rpo6/RPB6, Rpo6/Rpb6, DNA-dir_RNA_polK_14-18kDa_CS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	28
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	5
ganglionic eminence	3
ventricular zone	3
calcaneal tendon	3
stromal cell of endometrium	3
secondary oocyte	3
buccal mucosa cell	2
sural nerve	2
hypothalamus	2
male germ line stem cell (sensu Vertebrata) in testis	2
metanephric glomerulus	2
visceral pleura	2
pericardium	2
primordial germ cell in gonad	2
pancreatic ductal cell	2
periodontal ligament	1
ascending aorta	1
left coronary artery	1
right lung	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCF12	295	ubiquitous	marker	periodontal ligament, ventricular zone, ganglionic eminence
SPRY4	219	ubiquitous	marker	left coronary artery, right lung, ascending aorta
PROKR2	32	tissue_specific	yes	cortical plate, ganglionic eminence, ventricular zone
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
SEMA3A	194	ubiquitous	marker	stromal cell of endometrium, cortical plate, colonic epithelium
SEMA3E	197	broad	marker	cortical plate, calcaneal tendon, blood vessel layer
SOX10	218	broad	marker	inferior olivary complex, sural nerve, dorsal motor nucleus of vagus nerve
TACR3	43	tissue_specific	marker	cortical plate, secondary oocyte, hypothalamus
WDR11	287	ubiquitous	marker	epithelium of nasopharynx, nasopharynx, calcaneal tendon
PHIP	302	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, ventricular zone
IL17RD	236	broad	yes	secondary oocyte, oocyte, mammary duct
PROK2	159	broad	marker	blood, bone marrow, trabecular bone tissue
CHD7	269	ubiquitous	marker	secondary oocyte, cerebellar vermis, sural nerve
FEZF1	52	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, hypothalamus, caudate nucleus
NDNF	230	broad	marker	renal glomerulus, metanephric glomerulus, visceral pleura
CCDC141	149	broad	marker	heart left ventricle, adrenal tissue, right atrium auricular region
DCC	154	broad	marker	cortical plate, right testis, left testis
DUSP6	296	ubiquitous	marker	parotid gland, pericardium, monocyte
FGF17	154	tissue_specific	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
FGF8	109	tissue_specific	yes	primordial germ cell in gonad, metanephric glomerulus, endometrium epithelium
FLRT3	248	ubiquitous	marker	endothelial cell, lower lobe of lung, pericardium
HESX1	167	broad	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
HS6ST1	258	ubiquitous	marker	kidney epithelium, pancreatic ductal cell, ganglionic eminence
ANOS1	268	broad	marker	visceral pleura, hair follicle, skeletal muscle tissue of rectus abdominis
AXL	290	ubiquitous	marker	synovial joint, saphenous vein, stromal cell of endometrium
SRA1	254	ubiquitous	marker	pancreatic ductal cell, left adrenal gland, left adrenal gland cortex
PNPLA6	276	ubiquitous	marker	granulocyte, metanephros cortex, upper lobe of left lung
POLR2F	293	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 55.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
CHD7	4,819
FGF8	4,536
AXL	4,443
FGF17	3,908
SOX10	3,696
PHIP	3,057
PNPLA6	2,676
DUSP6	2,421
SEMA3A	2,069

Intra-cohort edges

A	B	Sources
ANOS1	CCDC141	string_interaction
ANOS1	CHD7	string_interaction
ANOS1	FEZF1	string_interaction
ANOS1	FGF8	string_interaction
ANOS1	FGFR1	biogrid_interaction, intact, string_interaction
ANOS1	FLRT3	string_interaction
ANOS1	HESX1	string_interaction
ANOS1	HS6ST1	string_interaction
ANOS1	NDNF	intact
ANOS1	PROK2	string_interaction
ANOS1	PROKR2	string_interaction
ANOS1	TACR3	string_interaction
CCDC141	FEZF1	string_interaction
CCDC141	HS6ST1	string_interaction
CCDC141	PROKR2	string_interaction
CCDC141	TACR3	string_interaction
CHD7	FEZF1	string_interaction
CHD7	PROK2	string_interaction
CHD7	PROKR2	string_interaction
CHD7	SEMA3E	string_interaction
CHD7	SOX10	biogrid_interaction
CHD7	TACR3	string_interaction
DUSP6	SPRY4	string_interaction
FEZF1	FLRT3	string_interaction
FEZF1	HS6ST1	string_interaction
FEZF1	IL17RD	string_interaction
FEZF1	PROK2	string_interaction
FEZF1	PROKR2	string_interaction
FEZF1	TACR3	string_interaction
FGF17	FGF8	intact
FGF17	FGFR1	string_interaction
FGF17	NDNF	string_interaction
FGF8	FGFR1	biogrid_interaction, intact, string_interaction
FGF8	IL17RD	string_interaction
FGF8	PROK2	string_interaction
FGF8	SPRY4	string_interaction
FGF8	WDR11	biogrid_interaction
FGFR1	PROK2	string_interaction
FGFR1	PROKR2	string_interaction
FGFR1	SPRY4	string_interaction
FGFR1	TACR3	string_interaction
FLRT3	IL17RD	string_interaction
FLRT3	PROKR2	string_interaction
FLRT3	SPRY4	string_interaction
HESX1	PROKR2	string_interaction
HS6ST1	IL17RD	string_interaction
HS6ST1	NDNF	string_interaction
HS6ST1	PROKR2	string_interaction
HS6ST1	TACR3	string_interaction
IL17RD	NDNF	string_interaction

Structural data

PDB: 16 · AlphaFold-only: 12 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHIP	Q8WWQ0	146
FGFR1	P11362	83
POLR2F	P61218	60
DCC	P43146	9
AXL	P30530	4
TACR3	P29371	3
CHD7	Q9P2D1	3
FLRT3	Q9NZU0	3
TCF12	Q99081	2
WDR11	Q9BZH6	2
DUSP6	Q16828	2
SRA1	Q9HD15	2
SPRY4	Q9C004	1
FGF8	P55075	1
HESX1	Q9UBX0	1
ANOS1	P23352	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HS6ST1	O60243	87.28
FGF17	O60258	86.39
SEMA3E	O15041	84.62
SEMA3A	Q14563	84.50
NDNF	Q8TB73	78.58
PROKR2	Q8NFJ6	78.50
CCDC141	Q6ZP82	72.36
PNPLA6	Q8IY17	69.75
IL17RD	Q8NFM7	69.68
PROK2	Q9HC23	69.22
SOX10	P56693	57.32
FEZF1	A0PJY2	56.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 194. Enrichment computed across 28 evidence-associated genes (22 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 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FGFR1c ligand binding and activation	4	138.4×	3e-06	FGFR1, FGF17, FGF8, ANOS1
Downstream signaling of activated FGFR1	4	98.9×	6e-06	FGFR1, FGF17, FGF8, FLRT3
Negative regulation of FGFR1 signaling	4	67.0×	2e-05	FGFR1, FGF17, FGF8, ANOS1
Signaling by activated point mutants of FGFR1	3	129.8×	7e-05	FGFR1, FGF17, FGF8
Phospholipase C-mediated cascade: FGFR1	3	91.6×	2e-04	FGFR1, FGF17, FGF8
PI-3K cascade:FGFR1	3	70.8×	3e-04	FGFR1, FGF17, FGF8
SHC-mediated cascade:FGFR1	3	67.7×	3e-04	FGFR1, FGF17, FGF8
FRS-mediated FGFR1 signaling	3	62.3×	3e-04	FGFR1, FGF17, FGF8
Signaling by FGFR1 in disease	3	39.9×	0.001	FGFR1, FGF17, FGF8
FGFR3b ligand binding and activation	2	148.3×	0.001	FGF17, FGF8
PI3K Cascade	3	37.1×	0.001	FGFR1, FGF17, FGF8
Signaling by FGFR2 in disease	3	36.2×	0.001	FGF17, FGF8, POLR2F
Signaling by activated point mutants of FGFR3	2	86.5×	0.003	FGF17, FGF8
FGFR3c ligand binding and activation	2	79.9×	0.003	FGF17, FGF8
FGFR2c ligand binding and activation	2	79.9×	0.003	FGF17, FGF8
Phospholipase C-mediated cascade; FGFR3	2	79.9×	0.003	FGF17, FGF8
FGFRL1 modulation of FGFR1 signaling	2	79.9×	0.003	FGF17, FGF8
FGFR4 ligand binding and activation	2	74.2×	0.003	FGF17, FGF8
Phospholipase C-mediated cascade; FGFR4	2	69.2×	0.004	FGF17, FGF8
Activated point mutants of FGFR2	2	61.1×	0.005	FGF17, FGF8
Phospholipase C-mediated cascade; FGFR2	2	57.7×	0.005	FGF17, FGF8
PI-3K cascade:FGFR3	2	57.7×	0.005	FGF17, FGF8
SHC-mediated cascade:FGFR3	2	54.6×	0.005	FGF17, FGF8
PI-3K cascade:FGFR4	2	51.9×	0.005	FGF17, FGF8
Constitutive Signaling by Aberrant PI3K in Cancer	3	17.3×	0.005	FGFR1, FGF17, FGF8
FRS-mediated FGFR3 signaling	2	49.4×	0.005	FGF17, FGF8
SHC-mediated cascade:FGFR4	2	49.4×	0.005	FGF17, FGF8
PI-3K cascade:FGFR2	2	45.1×	0.006	FGF17, FGF8
FRS-mediated FGFR4 signaling	2	45.1×	0.006	FGF17, FGF8
Signaling by FGFR3 in disease	2	45.1×	0.006	FGF17, FGF8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 28 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
axon guidance	6	19.4×	2e-04	SEMA3A, SEMA3E, FEZF1, DCC, FLRT3, ANOS1
fibroblast growth factor receptor signaling pathway	4	40.8×	3e-04	FGFR1, FGF17, FGF8, FLRT3
neuron migration	5	23.9×	3e-04	FGFR1, SEMA3A, NDNF, DCC, AXL
olfactory bulb development	3	82.1×	5e-04	SEMA3A, CHD7, FEZF1
dorsal/ventral axon guidance	2	300.9×	0.001	DCC, FGF8
gonadotrophin-releasing hormone neuronal migration to the hypothalamus	2	200.6×	0.002	SEMA3E, NDNF
chordate embryonic development	2	200.6×	0.002	FGFR1, CHD7
cell maturation	3	47.5×	0.002	FGFR1, SOX10, AXL
nose development	2	172.0×	0.002	CHD7, HESX1
blood vessel remodeling	3	41.0×	0.002	CHD7, FGF8, AXL
otic vesicle formation	2	150.5×	0.002	FGF8, HESX1
neural crest cell migration	3	36.1×	0.002	SEMA3A, SEMA3E, SOX10
negative regulation of neuron apoptotic process	4	15.8×	0.003	SEMA3E, NDNF, FGF8, AXL
vagina development	2	109.4×	0.004	TACR3, AXL
forebrain morphogenesis	2	100.3×	0.004	FGF8, HESX1
branching involved in salivary gland morphogenesis	2	100.3×	0.004	FGFR1, FGF8
organ induction	2	86.0×	0.005	FGFR1, FGF8
head development	2	86.0×	0.005	WDR11, FLRT3
gonad development	2	80.2×	0.005	FGF8, HESX1
positive regulation of neuron differentiation	3	21.2×	0.006	TCF12, FGFR1, FEZF1
aorta morphogenesis	2	63.4×	0.007	CHD7, FGF8
motor neuron axon guidance	2	50.1×	0.011	SEMA3A, FGF8
MAPK cascade	3	16.4×	0.012	FGFR1, DUSP6, FGF8
negative chemotaxis	2	46.3×	0.012	SEMA3A, SEMA3E
angiogenesis	4	8.9×	0.014	FGFR1, PROK2, NDNF, HS6ST1
embryonic hindlimb morphogenesis	2	41.5×	0.014	CHD7, FGF8
thyroid gland development	2	38.8×	0.014	FGF8, HESX1
cellular response to fibroblast growth factor stimulus	2	38.8×	0.014	FGFR1, NDNF
positive regulation of mitotic nuclear division	2	38.8×	0.014	PHIP, FGF8
branching involved in blood vessel morphogenesis	2	37.6×	0.014	SEMA3E, FGF8

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Menotropins.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 25

Druggability breadth: 8 of 28 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

Symbol	Example approved molecule
FGFR1	PONATINIB
TACR3	APREPITANT
AXL	GILTERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
AXL	59	4
TACR3	9	4
TCF12	0	0
SPRY4	0	0
PROKR2	0	0
SEMA3A	0	0
SEMA3E	0	0
SOX10	0	0
WDR11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	AXL, FGFR1
FEDRATINIB	4	AXL, FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	AXL, FGFR1
SORAFENIB	4	AXL, FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	AXL, FGFR1
CABOZANTINIB	4	AXL, FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	AXL, FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	AXL, FGFR1
DASATINIB	4	AXL, FGFR1
MIDOSTAURIN	4	AXL, FGFR1
APREPITANT	4	TACR3
FEZOLINETANT	4	TACR3
GILTERITINIB	4	AXL
AFATINIB	4	AXL
NERATINIB	4	AXL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
AXL	701	Binding:698, Functional:3
TACR3	266	Binding:217, Functional:48, ADMET:1
DUSP6	38	Binding:37, ADMET:1
PHIP	17	Binding:17
PROKR2	9	Functional:5, Binding:4
TCF12	1	Binding:1
PNPLA6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
DUSP6	3.1.3.16, 3.1.3.48	protein-serine/threonine phosphatase, protein-tyrosine-phosphatase
AXL	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FGFR1	1,465
TACR3	266
AXL	701

Pharmacogenomics

Cohort genes with a PharmGKB record: 28; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	AXL, FGFR1
FEDRATINIB	4	AXL, FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	AXL, FGFR1
SORAFENIB	4	AXL, FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	AXL, FGFR1
CABOZANTINIB	4	AXL, FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	AXL, FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	AXL, FGFR1
DASATINIB	4	AXL, FGFR1
MIDOSTAURIN	4	AXL, FGFR1
APREPITANT	4	TACR3
FEZOLINETANT	4	TACR3
GILTERITINIB	4	AXL
AFATINIB	4	AXL
NERATINIB	4	AXL

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	FGFR1, TACR3, AXL
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	4	DCC, DUSP6, FLRT3, ANOS1
D	Druggable family + AlphaFold only, no drug	5	PROKR2, SEMA3A, SEMA3E, NDNF, CCDC141
E	Difficult family or no structure, no drug	16	TCF12, SPRY4, SOX10, WDR11, PHIP, IL17RD, PROK2, CHD7, FEZF1, FGF17 (+6 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FGF17	0	FGFR1
FGF8	0	FGFR1
ANOS1	0	FGFR1
TCF12	1	—
SPRY4	0	—
PROKR2	9	—
SEMA3A	0	—
SEMA3E	0	—
SOX10	0	—
WDR11	0	—
PHIP	17	—
IL17RD	0	—
PROK2	0	—
CHD7	0	—
FEZF1	0	—
NDNF	0	—
CCDC141	0	—
DCC	0	—
DUSP6	38	—
FLRT3	0	—
HESX1	0	—
HS6ST1	0	—
SRA1	0	—
PNPLA6	1	—
POLR2F	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 17.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE1	5
PHASE4	3
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT00064987	PHASE2	TERMINATED	Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
NCT00392756	PHASE1	COMPLETED	Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
NCT00493961	PHASE1	COMPLETED	Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism
NCT00914823	PHASE1	COMPLETED	Kisspeptin Administration in the Adult
NCT01438034	PHASE1	COMPLETED	Kisspeptin in the Evaluation of Delayed Puberty
NCT03118479	PHASE1	TERMINATED	Effect of Varying Testosterone Levels on Insulin Sensitivity in Men With Idiopathic Hypogonadotropic Hypogonadism (IHH)
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04733274	Not specified	ACTIVE_NOT_RECRUITING	Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing
NCT05971836	Not specified	ACTIVE_NOT_RECRUITING	The Molecular Basis of Inherited Reproductive Disorders
NCT00392457	Not specified	COMPLETED	Investigating the Regulation of Reproductive Hormones in Adult Men
NCT00494169	Not specified	COMPLETED	Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders
NCT00623116	Not specified	UNKNOWN	A Study to Characterize Epidemiology, Clinical and Genetic Features of Kallmann Syndrome in Finland
NCT01914172	Not specified	COMPLETED	Health Needs of Patients With Kallmann Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GONADORELIN ACETATE	4	2
GONADOTROPIN, CHORIONIC	4	2
ANASTROZOLE	4	1
MENOTROPINS	4	1
KISSPEPTIN	2	2
CHEMBL2370644	0	2