Ectodermal dysplasia syndrome

Summary

Ectodermal dysplasia syndrome (MONDO:0019287) is a disease (an umbrella term covering 120 Mondo subtypes) caused by variants in SMARCAD1, CTSC, and RIPK4, with 13 cohort genes and 8 clinical trials. The dominant Reactome pathway is TNFs bind their physiological receptors (3 cohort genes).

At a glance

• Prevalence: 6-9 / 10 000 (Worldwide) [Orphanet-validated]
• Causal genes: SMARCAD1 (GenCC Definitive), CTSC (GenCC Strong), RIPK4 (GenCC Strong)
• Umbrella term: 120 Mondo subtypes
• Cohort genes: 13
• ClinVar variants: 20
• Clinical trials: 8

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	6-9 / 10 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	ectodermal dysplasia syndrome
Mondo ID	MONDO:0019287
MeSH	D004476
OMIM	305100
Orphanet	79373
DOID	DOID:2121
ICD-11	1156567558
NCIT	C84683
SNOMED CT	8654005
UMLS	C0013575
MedGen	8544
GARD	0006317
MedDRA	10010452
Is cancer (heuristic)	no

Also known as: ectodermal dysplasia · ectodermal dysplasia (select examples)

Data availability: 20 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 120 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia 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, 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, 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 (120): ADULT syndrome, autosomal dominant palmoplantar keratoderma and congenital alopecia, ameloonychohypohidrotic syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, anonychia with flexural pigmentation, Böök syndrome, blepharocheilodontic syndrome, Stern-Lubinsky-Durrie syndrome, dermatopathia pigmentosa reticularis, dermo-odonto dysplasia, Rapp-Hodgkin syndrome, Clouston syndrome, ectodermal dysplasia, trichoodontoonychial type, gingival fibromatosis-hypertrichosis syndrome, hypertrichosis cubiti-short stature syndrome, Johnson neuroectodermal syndrome, Marshall syndrome, Naegeli-Franceschetti-Jadassohn syndrome, oculodentodigital dysplasia, Cronkhite-Canada syndrome, scalp-ear-nipple syndrome, tooth and nail syndrome, tricho-dento-osseous syndrome, tricho-retino-dento-digital syndrome, acrofacial dysostosis, Weyers type, Ackerman syndrome, alopecia - contractures - dwarfism - intellectual disability syndrome, AREDYLD syndrome, Barber-Say syndrome, oculoosteocutaneous syndrome, cataract-hypertrichosis-intellectual disability syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, cerebellar ataxia-ectodermal dysplasia syndrome, cranioectodermal dysplasia, conductive deafness-ptosis-skeletal anomalies syndrome, dermatoosteolysis, Kirghizian type, Dubowitz syndrome, ectodermal dysplasia-sensorineural deafness syndrome, ectodermal dysplasia-intellectual disability-central nervous system malformation syndrome, hypohidrotic ectodermal dysplasia-hypothyroidism-ciliary dyskinesia syndrome, cleft lip/palate-ectodermal dysplasia syndrome, EEM syndrome, Ellis-van Creveld syndrome, amelocerebrohypohidrotic syndrome, GAPO syndrome, ichthyosis-alopecia-eclabion-ectropion-intellectual disability syndrome, Leukomelanoderma-infantilism-intellectual disability-hypodontia-hypotrichosis syndrome, Dahlberg-Borer-Newcomer syndrome, cartilage-hair hypoplasia, oculotrichodysplasia, pilodental dysplasia-refractive errors syndrome, Bartsocas-Papas syndrome 1, ectodermal dysplasia-blindness syndrome, Schinzel-Giedion syndrome, Teebi-Shaltout syndrome, taurodontia-absent teeth-sparse hair syndrome, odontotrichomelic syndrome, trichomegaly-retina pigmentary degeneration-dwarfism syndrome, trichoodontoonychial dysplasia, CHIME syndrome, anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome, Ito hypomelanosis, contractures-ectodermal dysplasia-cleft lip/palate syndrome, incontinentia pigmenti, Toriello-Lacassie-Droste syndrome, odontomicronychial dysplasia, ectodermal dysplasia with natal teeth, Turnpenny type, hidrotic ectodermal dysplasia, Christianson-Fourie type, trichodental syndrome, congenital hypotrichosis with juvenile macular dystrophy, tricho-oculo-dermo-vertebral syndrome, odonto-tricho-ungual-digito-palmar syndrome, Fried’s tooth and nail syndrome, limb-mammary syndrome, epidermolysis bullosa simplex due to plakophilin deficiency, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, Curly hair - acral keratoderma - caries syndrome, hypotrichosis-osteolysis-periodontitis-palmoplantar keratoderma syndrome, Lelis syndrome, Fontaine progeroid syndrome, ectodermal dysplasia-syndactyly syndrome, ectodermal dysplasia 5, hair/nail type, nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome, ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type, cardiofaciocutaneous syndrome, choroidal atrophy-alopecia syndrome, dyskeratosis congenita, hidrotic ectodermal dysplasia, Halal type, hypertrichosis lanuginosa congenita, hypohidrotic ectodermal dysplasia, odonto-onycho dysplasia-alopecia syndrome, pili torti-onychodysplasia syndrome, chondroectodermal dysplasia with night blindness, trichorhinophalangeal syndrome, trichothiodystrophy, trichodermodysplasia-dental alterations syndrome, autosomal dominant trichoodontoonychodysplasia-syndactyly, focal facial dermal dysplasia, KID syndrome, pure hair and nail ectodermal dysplasia, circumscribed palmoplantar hypokeratosis, trichodysplasia-amelogenesis imperfecta syndrome, dermotrichic syndrome, alves Castelo dos Santos syndrome, Brunoni syndrome, ectodermal dysplasia Bartalos type, ectodermal dysplasia margarita type, ectodermal dysplasia alopecia preaxial polydactyly, ectodermal dysplasia arthrogryposis diabetes mellitus, ectodermal dysplasia blindness, ectodermal dysplasia neurosensory deafness, ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, ectodermal dysplasia 15, hypohidrotic/hair type, linear hypopigmentation and craniofacial asymmetry with acral, ocular and brain anomalies, jones hersh yusk syndrome, ectodermal dysplasia 13, hair/tooth type, arthrogryposis-ectodermal dysplasia-other anomalies syndrome, ectodermal dysplasia WNT10A related, CTSC-related disorder, ectodermal dysplasia 17 with or without limb malformations

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

20 retrieved; paginated sample, class counts are floors:

7 pathogenic, 6 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
545741	NM_004655.4(AXIN2):c.1994dup (p.Asn666fs)	AXIN2	Pathogenic	criteria provided, multiple submitters, no conflicts
4087738	NM_177986.5(DSG4):c.1168_1172dup (p.Phe392fs)	DSG1-AS1	Pathogenic	criteria provided, single submitter
11037	NM_001399.5(EDA):c.467G>A (p.Arg156His)	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
228257	NM_001399.5(EDA):c.866G>A (p.Arg289His)	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31908	NM_001399.5(EDA):c.826C>T (p.Arg276Cys)	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
504887	NM_022336.4(EDAR):c.529+1G>A	EDAR	Pathogenic	criteria provided, single submitter
5860	NM_022336.4(EDAR):c.803+1G>A	EDAR	Pathogenic	no assertion criteria provided
2713690	NM_144991.3(TSPEAR):c.1574G>A (p.Gly525Asp)	LOC126653398	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4533369	NM_002336.3(LRP6):c.3885_3892del (p.Cys1295fs)	LRP6	Pathogenic	criteria provided, single submitter
4075221	NM_001114980.2(TP63):c.2T>G (p.Met1Arg)	TP63	Pathogenic	criteria provided, single submitter
403572	NM_144991.3(TSPEAR):c.589C>T (p.Arg197Ter)	TSPEAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2947564	NM_025216.3(WNT10A):c.844G>T (p.Glu282Ter)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4461	NM_025216.3(WNT10A):c.321C>A (p.Cys107Ter)	WNT10A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5848	NM_022336.4(EDAR):c.52-25_52-8del	EDAR	Likely pathogenic	criteria provided, single submitter
986783	NM_022336.4(EDAR):c.338G>A (p.Cys113Tyr)	EDAR	Likely pathogenic	criteria provided, single submitter
4539015	NM_022336.4(EDAR):c.1084dup (p.Ser362fs)	RANBP2	Likely pathogenic	criteria provided, single submitter
840729	NM_022336.4(EDAR):c.1130T>C (p.Leu377Pro)	EDAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227135	NM_144991.3(TSPEAR):c.1915G>A (p.Asp639Asn)	TSPEAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4462	NM_025216.3(WNT10A):c.682T>A (p.Phe228Ile)	WNT10A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
262601	NM_145861.4(EDARADD):c.308C>T (p.Ser103Phe)	EDARADD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 34 · 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
SMARCAD1	Definitive	Autosomal dominant	ectodermal dysplasia syndrome	7
CTSC	Strong	Autosomal recessive	ectodermal dysplasia syndrome	10
RIPK4	Strong	Autosomal recessive	ectodermal dysplasia syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCAD1	Orphanet:1658	Absence of fingerprints-congenital milia syndrome
SMARCAD1	Orphanet:289465	Isolated congenital adermatoglyphia
SMARCAD1	Orphanet:384	Huriez syndrome
CTSC	Orphanet:2342	Haim-Munk syndrome
CTSC	Orphanet:678	Papillon-Lefèvre syndrome
RIPK4	Orphanet:1234	Bartsocas-Papas syndrome
RIPK4	Orphanet:1401	CHAND syndrome
TSPEAR	Orphanet:685067	Hypodontia-scalp hypotrichosis-facial dysmorphism syndrome
WNT10A	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
WNT10A	Orphanet:2721	Odonto-onycho-dermal dysplasia
WNT10A	Orphanet:50944	Schöpf-Schulz-Passarge syndrome
WNT10A	Orphanet:99798	Oligodontia
EDARADD	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
EDARADD	Orphanet:99798	Oligodontia
TP63	Orphanet:1072	Ankyloblepharon filiforme adnatum-cleft palate syndrome
TP63	Orphanet:141291	Cleft lip and alveolus
TP63	Orphanet:1896	EEC syndrome
TP63	Orphanet:199302	Isolated cleft lip
TP63	Orphanet:199306	Cleft lip/palate
TP63	Orphanet:2440	Isolated split hand-split foot malformation
TP63	Orphanet:69085	Limb-mammary syndrome
TP63	Orphanet:93930	Classic bladder exstrophy
TP63	Orphanet:978	ADULT syndrome
EDAR	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDAR	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
EDA	Orphanet:181	X-linked hypohidrotic ectodermal dysplasia
EDA	Orphanet:99798	Oligodontia
LRP6	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
LRP6	Orphanet:99798	Oligodontia
AXIN2	Orphanet:401911	AXIN2-related polyposis
RANBP2	Orphanet:178342	Inflammatory myofibroblastic tumor
RANBP2	Orphanet:263524	Acute necrotizing encephalopathy of childhood
RANBP2	Orphanet:88619	Familial acute necrotizing encephalopathy

Cohort genes → proteins

13 cohort genes, 12 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCAD1	HGNC:18398	ENSG00000163104	Q9H4L7	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1	gencc
CTSC	HGNC:2528	ENSG00000109861	P53634	Dipeptidyl peptidase 1	gencc
RIPK4	HGNC:496	ENSG00000183421	P57078	Receptor-interacting serine/threonine-protein kinase 4	gencc
TSPEAR	HGNC:1268	ENSG00000175894	Q8WU66	Thrombospondin-type laminin G domain and EAR repeat-containing protein	clinvar
WNT10A	HGNC:13829	ENSG00000135925	Q9GZT5	Protein Wnt-10a	clinvar
EDARADD	HGNC:14341	ENSG00000186197	Q8WWZ3	Ectodysplasin-A receptor-associated adapter protein	clinvar
TP63	HGNC:15979	ENSG00000073282	Q9H3D4	Tumor protein 63	clinvar
EDAR	HGNC:2895	ENSG00000135960	Q9UNE0	Tumor necrosis factor receptor superfamily member EDAR	clinvar
EDA	HGNC:3157	ENSG00000158813	Q92838	Ectodysplasin-A	clinvar
DSG1-AS1	HGNC:51115	ENSG00000266729		DSG1 antisense RNA 1	clinvar
LRP6	HGNC:6698	ENSG00000070018	O75581	Low-density lipoprotein receptor-related protein 6	clinvar
AXIN2	HGNC:904	ENSG00000168646	Q9Y2T1	Axin-2	clinvar
RANBP2	HGNC:9848	ENSG00000153201	P49792	E3 SUMO-protein ligase RanBP2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCAD1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1	Protein that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization.
CTSC	Dipeptidyl peptidase 1	Thiol protease.
RIPK4	Receptor-interacting serine/threonine-protein kinase 4	Serine/threonine protein kinase.
TSPEAR	Thrombospondin-type laminin G domain and EAR repeat-containing protein	Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.
WNT10A	Protein Wnt-10a	Ligand for members of the frizzled family of seven transmembrane receptors.
EDARADD	Ectodysplasin-A receptor-associated adapter protein	Adapter protein that interacts with EDAR DEATH domain and couples the receptor to EDA signaling pathway during morphogenesis of ectodermal organs.
TP63	Tumor protein 63	Acts as a sequence specific DNA binding transcriptional activator or repressor.
EDAR	Tumor necrosis factor receptor superfamily member EDAR	Receptor for EDA isoform A1, but not for EDA isoform A2.
EDA	Ectodysplasin-A	Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs.
LRP6	Low-density lipoprotein receptor-related protein 6	Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes.
AXIN2	Axin-2	Inhibitor of the Wnt signaling pathway.
RANBP2	E3 SUMO-protein ligase RanBP2	E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 9 · Druggable fraction: 0.15

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
Protease	1	2.8×	0.479
Kinase	1	2.1×	0.479
Transcription factor	2	1.3×	0.479
Other/Unknown	9	1.2×	0.479

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCAD1	Other/Unknown	no		SNF2_N, Helicase_C-like, CUE
CTSC	Protease	yes	3.4.14.1	Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A
RIPK4	Kinase	yes		Prot_kinase_dom, Ankyrin_rpt, Ser/Thr_kinase_AS
TSPEAR	Other/Unknown	no		EPTP, EAR, ConA-like_dom_sf
WNT10A	Other/Unknown	no		Wnt, Wnt10, Wnt_CS
EDARADD	Other/Unknown	no		Death_dom, DEATH-like_dom_sf, EDARADD
TP63	Transcription factor	no		SAM, p53_tumour_suppressor, p53-like_TF_DNA-bd_sf
EDAR	Other/Unknown	no		DEATH-like_dom_sf, EDAR_N, TNR19/27/EDAR
EDA	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_Ligand_Superfamily
DSG1-AS1	Other/Unknown	no
LRP6	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
AXIN2	Other/Unknown	no		DIX, Axin_b-cat-bd, RGS
RANBP2	Transcription factor	no		Ran_bind_dom, Znf_RanBP2, Cyclophilin-type_PPIase_dom

Expression context

Cohort genes with no expression data: 0.

11 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
tongue squamous epithelium	2
primordial germ cell in gonad	2
lower esophagus mucosa	2
upper arm skin	2
oocyte	2
adrenal tissue	1
ganglionic eminence	1
tibia	1
epithelium of nasopharynx	1
nasopharynx	1
palpebral conjunctiva	1
epithelium of esophagus	1
esophagus squamous epithelium	1
adenohypophysis	1
pituitary gland	1
bone marrow cell	1
islet of Langerhans	1
sural nerve	1
skin of hip	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCAD1	245	ubiquitous	marker	adrenal tissue, ganglionic eminence, tibia
CTSC	285	ubiquitous	marker	palpebral conjunctiva, epithelium of nasopharynx, nasopharynx
RIPK4	182	broad	marker	esophagus squamous epithelium, tongue squamous epithelium, epithelium of esophagus
TSPEAR	88	tissue_specific	yes	primordial germ cell in gonad, adenohypophysis, pituitary gland
WNT10A	151	broad	marker	primordial germ cell in gonad, lower esophagus mucosa, bone marrow cell
EDARADD	147	broad	marker	islet of Langerhans, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
TP63	207	broad	marker	upper leg skin, skin of hip, upper arm skin
EDAR	100	tissue_specific	yes	secondary oocyte, oocyte, pancreatic ductal cell
EDA	175	broad	marker	tongue squamous epithelium, male germ line stem cell (sensu Vertebrata) in testis, oocyte
DSG1-AS1	96	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, esophagus mucosa, lower esophagus mucosa
LRP6	139	ubiquitous	marker	calcaneal tendon, corpus callosum, ventricular zone
AXIN2	221	ubiquitous	marker	oviduct epithelium, upper arm skin, body of uterus
RANBP2	294	ubiquitous	marker	endothelial cell, sperm, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RANBP2	7,348
RIPK4	5,738
AXIN2	3,049
TP63	2,893
SMARCAD1	2,862
CTSC	2,733
LRP6	2,525
EDAR	1,307
WNT10A	1,092
TSPEAR	839

Intra-cohort edges

A	B	Sources
AXIN2	EDARADD	string_interaction
AXIN2	WNT10A	string_interaction
EDA	EDAR	intact, string_interaction
EDA	EDARADD	string_interaction
EDA	WNT10A	string_interaction
EDAR	EDARADD	biogrid_interaction, intact, string_interaction
EDAR	WNT10A	string_interaction
EDARADD	WNT10A	string_interaction
LRP6	RIPK4	intact
LRP6	WNT10A	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 4 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RANBP2	P49792	33
LRP6	O75581	30
TP63	Q9H3D4	26
CTSC	P53634	18
SMARCAD1	Q9H4L7	4
EDA	Q92838	3
EDAR	Q9UNE0	1
AXIN2	Q9Y2T1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPEAR	Q8WU66	87.47
WNT10A	Q9GZT5	82.36
RIPK4	P57078	75.41
EDARADD	Q8WWZ3	73.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 84. Enrichment computed across 13 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TNFs bind their physiological receptors	3	131.3×	1e-04	EDARADD, EDAR, EDA
Signaling by RNF43 mutants	1	141.0×	0.067	LRP6
Activation of PUMA and translocation to mitochondria	1	126.9×	0.067	TP63
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	126.9×	0.067	AXIN2
TP53 Regulates Transcription of Caspase Activators and Caspases	1	105.7×	0.067	TP63
TP53 Regulates Transcription of Death Receptors and Ligands	1	105.7×	0.067	TP63
Regulation of TP53 Activity through Association with Co-factors	1	90.6×	0.067	TP63
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	84.6×	0.067	TP63
Developmental Lineage of Mammary Stem Cells	1	84.6×	0.067	TP63
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	79.3×	0.067	LRP6
Repression of WNT target genes	1	79.3×	0.067	AXIN2
Signaling by WNT in cancer	1	66.8×	0.067	LRP6
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	60.4×	0.067	TP63
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	60.4×	0.067	TP63
Regulation of FZD by ubiquitination	1	57.7×	0.067	LRP6
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	50.8×	0.067	TP63
WNT ligand biogenesis and trafficking	1	47.0×	0.067	WNT10A
Pyroptosis	1	47.0×	0.067	TP63
IPs transport between nucleus and cytosol	1	42.3×	0.067	RANBP2
IP3 and IP4 transport between cytosol and nucleus	1	42.3×	0.067	RANBP2
IP6 and IP7 transport between cytosol and nucleus	1	42.3×	0.067	RANBP2
Transport of Ribonucleoproteins into the Host Nucleus	1	39.6×	0.067	RANBP2
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	39.6×	0.067	RANBP2
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	39.6×	0.067	LRP6
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	39.6×	0.067	RANBP2
NEP/NS2 Interacts with the Cellular Export Machinery	1	38.5×	0.067	RANBP2
Nuclear import of Rev protein	1	37.3×	0.067	RANBP2
Vpr-mediated nuclear import of PICs	1	37.3×	0.067	RANBP2
Cargo concentration in the ER	1	37.3×	0.067	CTSC
Transport of the SLBP independent Mature mRNA	1	36.2×	0.067	RANBP2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
odontogenesis	3	131.7×	1e-04	WNT10A, EDA, AXIN2
canonical Wnt signaling pathway	4	51.1×	1e-04	WNT10A, EDA, LRP6, AXIN2
salivary gland cavitation	2	561.7×	2e-04	EDAR, EDA
odontogenesis of dentin-containing tooth	3	75.2×	3e-04	TP63, EDAR, EDA
neural crest cell differentiation	2	255.3×	7e-04	WNT10A, LRP6
pigmentation	2	117.0×	0.003	EDAR, EDA
positive regulation of apoptotic signaling pathway	2	96.8×	0.004	TP63, CTSC
hair follicle morphogenesis	2	82.6×	0.005	WNT10A, TP63
skin development	2	73.9×	0.005	WNT10A, RIPK4
hair follicle development	2	63.8×	0.006	WNT10A, EDAR
ectoderm and mesoderm interaction	1	1404.3×	0.007	TP63
epidermal cell division	1	1404.3×	0.007	TP63
regulation of mismatch repair	1	1404.3×	0.007	AXIN2
regulation of chondrocyte development	1	1404.3×	0.007	AXIN2
stem cell proliferation	2	52.0×	0.007	TP63, AXIN2
positive regulation of non-canonical NF-kappaB signal transduction	2	42.6×	0.009	EDAR, EDA
cloacal septation	1	702.2×	0.010	TP63
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	702.2×	0.010	TP63
trachea gland development	1	702.2×	0.010	EDA
positive regulation of somatic stem cell population maintenance	1	702.2×	0.010	TP63
regulation of epidermal cell division	1	468.1×	0.013	TP63
tooth mineralization	1	468.1×	0.013	TSPEAR
female genitalia morphogenesis	1	468.1×	0.013	TP63
regulation of centromeric sister chromatid cohesion	1	468.1×	0.013	AXIN2
negative regulation of mesoderm development	1	468.1×	0.013	TP63
regulation of DNA recombination	1	351.1×	0.014	SMARCAD1
chromosome separation	1	351.1×	0.014	SMARCAD1
prostatic bud formation	1	351.1×	0.014	TP63
obsolete positive regulation of proteolysis involved in protein catabolic process	1	351.1×	0.014	CTSC
Notch signaling pathway	2	23.6×	0.015	TSPEAR, TP63

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 11

Druggability breadth: 6 of 13 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.

Symbol	Example approved molecule
CTSC	OSIMERTINIB
RIPK4	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RIPK4	15	4
CTSC	3	4
SMARCAD1	0	0
TSPEAR	0	0
WNT10A	0	0
EDARADD	0	0
TP63	0	0
EDAR	0	0
EDA	0	0
DSG1-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OSIMERTINIB	4	CTSC
FEDRATINIB	4	RIPK4
AXITINIB	4	RIPK4
RUXOLITINIB	4	RIPK4
VANDETANIB	4	RIPK4
NINTEDANIB	4	RIPK4
SUNITINIB	4	RIPK4
ERLOTINIB	4	RIPK4
CRIZOTINIB	4	RIPK4
CANERTINIB	3	CTSC
BRENSOCATIB	3	CTSC
LESTAURTINIB	3	RIPK4
FORETINIB	2	RIPK4
TG100-115	2	RIPK4
R-406	2	RIPK4
TOZASERTIB	2	RIPK4
KW-2449	1	RIPK4
AST-487	1	RIPK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CTSC	107	Binding:106, ADMET:1
RIPK4	91	Binding:91
AXIN2	14	Binding:14
LRP6	9	Binding:9
EDAR	1	Binding:1
RANBP2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CTSC	3.4.14.1	dipeptidyl-peptidase I

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CTSC	107

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

18 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)
OSIMERTINIB	4	CTSC
FEDRATINIB	4	RIPK4
AXITINIB	4	RIPK4
RUXOLITINIB	4	RIPK4
VANDETANIB	4	RIPK4
NINTEDANIB	4	RIPK4
SUNITINIB	4	RIPK4
ERLOTINIB	4	RIPK4
CRIZOTINIB	4	RIPK4
CANERTINIB	3	CTSC
BRENSOCATIB	3	CTSC
LESTAURTINIB	3	RIPK4
FORETINIB	2	RIPK4
TG100-115	2	RIPK4
R-406	2	RIPK4
TOZASERTIB	2	RIPK4
KW-2449	1	RIPK4
AST-487	1	RIPK4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CTSC, RIPK4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	11	SMARCAD1, TSPEAR, WNT10A, EDARADD, TP63, EDAR, EDA, DSG1-AS1, LRP6, AXIN2 (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SMARCAD1	0	—
TSPEAR	0	—
WNT10A	0	—
EDARADD	0	—
TP63	0	—
EDAR	1	—
EDA	0	—
DSG1-AS1	0	—
LRP6	9	—
AXIN2	14	—
RANBP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT07468019	Not specified	RECRUITING	Organization’s Unique Protocol ID
NCT00001211	Not specified	COMPLETED	Clinical Study of Oral Endosseous Titanium Implants in Edentulous Subjects
NCT00266513	Not specified	TERMINATED	Studies of Disorders in Antibody Production and Related Primary Immunodeficiency States
NCT01108770	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia
NCT02896387	Not specified	TERMINATED	Ability of a Molecule (Prima) to Restore Physiological Differentiation in Epithelium Expressing Gene p63