Tourette syndrome

disease
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Also known as Gilles de la Tourette syndromeGTSmotor-verbal tic disorderTourette diseaseTourette's syndrome

Summary

Tourette syndrome (MONDO:0007661) is a disease with 57 cohort genes (223 GWAS associations across 15 studies) and 183 clinical trials. The dominant Reactome pathway is TP53 Regulates Transcription of Death Receptors and Ligands (3 cohort genes). Top therapeutic interventions include valbenazine, aripiprazole, and guanfacine.

At a glance

  • Cohort genes: 57
  • GWAS associations: 223
  • ClinVar variants: 100
  • Clinical trials: 183

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameTourette syndrome
Mondo IDMONDO:0007661
EFOEFO:0004895
MeSHD005879
OMIM137580
Orphanet856
DOIDDOID:11119
ICD-10-CMF95.2
ICD-11119340957
NCITC35078
SNOMED CT5158005
UMLSC0040517
MedGen21219
Is cancer (heuristic)no

Also known as: Gilles de la Tourette syndrome · GTS · motor-verbal tic disorder · Tourette disease · Tourette syndrome · Tourette’s syndrome

Data availability: 100 ClinVar variants · 223 GWAS associations (15 studies) · 79 GenCC gene-disease records · 145 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic diseaseTourette 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, 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, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, Usher syndrome, obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome, CREST syndrome, Sheehan syndrome, polymyalgia rheumatica, autoinflammatory syndrome, neuroleptic malignant syndrome, pituitary stalk interruption syndrome, monosomy 13q34, ring chromosome 13, 48,XXXY syndrome, 49,XXXXY syndrome, hereditary continuous muscle fiber activity, Eisenmenger syndrome, Robinow syndrome, Ehlers-Danlos syndrome, hypoplastic right heart syndrome, shone complex, 48,XYYY syndrome, subcortical band heterotopia, complex regional pain syndrome type 2, faciodigitogenital syndrome, neoplastic syndrome, paraneoplastic syndrome, post-infectious syndrome, Achard-Thiers syndrome, acral dysostosis dyserythropoiesis syndrome, agnathia-microstomia-synotia, Aksu von Stockhausen syndrome, Aloi Tomasini Isaia syndrome, temporomandibular joint dysfunction syndrome, Apert-like polydactyly syndrome, arakawa syndrome 2, arena syndrome, Arnold stickler bourne syndrome, baetz-greenwalt syndrome, bagatelle Cassidy syndrome, baker Vinters syndrome, bobble-head doll syndrome, Boerhaave syndrome, Cantu Sanchez-Corona Fragoso syndrome, Cantu Sanchez-Corona Hernandez syndrome, carbon baby syndrome, Carnevale hernandez castillo syndrome, Cartwright Nelson Fryns syndrome, Charles bonnet syndrome, Parinaud syndrome, corticobasal degeneration disorder, hair defect with photosensitivity and intellectual disability syndrome, AIDS dysmorphic syndrome, congenital acardia, acute lymphoblastic leukemia congenital sporadic aniridia, aglossia and situs inversus, agyria pachygyria polymicrogyria, agyria-pachygyria type 1, Ahumada Del Castillo syndrome, alopecia congenita keratosis palmoplantaris, alpha-mannosidosis type 1, aluminosis, Mauriac syndrome, ankle defects short stature, ankyloblepharon filiforme imperforate anus, annular constricting bands, anophthalmia cleft palate micrognathia, anophthalmia esophageal atresia cryptorchidism, anotia facial palsy cardiac defect, aortic dissection lentiginosis, childhood aortic valve stenosis, arthrogryposis IUGR thoracic dystrophy, arthrogryposis multiplex congenita CNS calcification, arthrogryposis spinal muscular atrophy, asternia, atlanto-axial fusion, atrophoderma of Pierini and Pasini, Barnicoat Baraitser syndrome, Basedow’s coma, BD syndrome, Beardwell syndrome, bhaskar jagannathan syndrome, bidirectional tachycardia, bilirubin induced brain injury in the newborn, blepharo naso facial syndrome van Maldergem type, bone dysplasia corpus callosum agenesis, brachydactyly absence of distal phalanges, brachydactyly anonychia, brachydactyly small stature face anomalies, brachydactyly tibial hypoplasia, brittle bone syndrome lethal type, bronchiectasis oligospermia, Brunsting-Perry syndrome, bruyn scheltens syndrome, burn goodship syndrome, camptodactyly joint contractures and facial skeletal dysplasia, camptodactyly vertebral fusion, Cantu Sanchez-Corona Garcia-Cruz syndrome, cardiac hydatid cysts with intracavitary expansion, cardioencephalomyopathy, cardiofacial syndrome short limbs, cardiomelic syndrome stratton Koehler type, cardiomyopathy and deafness due to tRNA lysine gene mutation, cardiomyopathy diabetes deafness, cardiomyopathy hypogonadism collagenoma syndrome, cardiomyopathy hypogonadism metabolic anomalies, cardiomyopathy spherocytosis, carpo tarsal osteolysis recessive, autosomal dominant cataract, cataract skeletal anomalies, cennamo gangemi syndrome, cerebellar agenesis, cerebello-olivary atrophy, cerebral calcification cerebellar hypoplasia, cerebral calcifications opalescent teeth phosphaturia, oculo digital syndrome, chondrodysplasia, choreoacanthocytosis amyotrophic, chorioretinopathy dominant form microcephaly, Christian Demyer Franken syndrome, Christian Johnson angenieta syndrome, chromosome 3 duplication syndrome, chronic demyelinizing neuropathy with IgM monoclonal, ciliary dyskinesia-bronchiectasis, circumscribed cutaneous aplasia of the vertex, circumscribed disseminated keratosis Jadassohn lew type, cleft lip and palate malrotation cardiopathy, cleft lip and/or palate with mucous cysts of lower, cleft lip palate dysmorphism kumar type, cleft lip palate intellectual disability corneal opacity, cleft lip palate oligodontia syndactyly pili torti, cleft lip palate pituitary deficiency, cleft lip palate-tetraphocomelia, cleft lower lip cleft lateral canthi chorioretinal, cleft palate cardiac defect ectrodactyly, cleft palate colobomata radial synostosis deafness, cleft palate heart disease polydactyly absent tibia, cleft tongue, coarse face hypotonia constipation, Cohen Lockood Wyborney syndrome, type 2 collagenopathy, Collins-Sakati syndrome, coloboma porencephaly hydronephrosis, colobomata unilobar lung heart defect, colonic malakoplakia, Colver Steer Godman syndrome, Combarros Calleja Leno syndrome, complement receptor deficiency, congenital absence of the sternocleidomastoid muscle, congenital amputation, congenital aneurysms of the great vessels, congenital articular rigidity, congenital benign spinal muscular atrophy dominant, congenital cardiovascular shunt, congenital contractures, congenital craniosynostosis maternal hyperthyroiditis, congenital cystic eye, congenital heart disease ptosis hypodontia craniostosis, congenital heart disease radio ulnar synostosis intellectual disability, congenital mumps, congenital stenosis of cervical medullary canal, Dennis-Fairhurst-Moore syndrome, congenital unilateral pulmonary hypoplasia, congenital vagal hyperreflexivity, Cormier Rustin Munnich syndrome, corneal crystals myopathy neuropathy, corneal dystrophy ichthyosis microcephaly intellectual disability, corneal dystrophy pigmentary anomaly malabsorption, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cortada Koussef Matsumoto syndrome, Cortes Lacassie syndrome, craniofacial and skeletal defects, craniofacial dysostosis arthrogryposis progeroid appearance, craniofrontonasal syndrome Teebi type, craniostenosis with congenital heart disease intellectual disability, crawfurd syndrome, cutis gyratum acanthosis nigricans craniosynostosis, cutis laxa osteoporosis, Davenport-Donlan syndrome, Davis Lafer syndrome, de Hauwere Leroy adriaenssens syndrome, deafness conductive stapedial ear malformation facial palsy, deafness goiter stippled epiphyses, deafness hypospadias metacarpal and metatarsal syndrome, deafness mesenteric diverticula of small bowel neuropathy, deafness peripheral neuropathy arterial disease, deafness progressive cataract autosomal dominant, dermatocardioskeletal syndrome boronne type, dextrocardia with situs inversus, diabetes persistent mullerian ducts, diaphragmatic agenesis radial aplasia omphalocele, diaphragmatic hernia exomphalos corpus callosum agenesis, diaphragmatic hernia upper limb defects, die Smulders droog van dijk syndrome, diomedi bernardi placidi syndrome, diphallus rachischisis imperforate anus, distichiasis heart congenital anomalies, double discordia, double uterus-hemivagina-renal agenesis, Drachtman Weinblatt Sitarz syndrome, Duker-Weiss-Siber syndrome, duodenal atresia tetralogy of fallot, duplication of leg mirror foot, duplication of the thumb unilateral biphalangeal, dupont sellier chochillon syndrome, dwarfism bluish sclerae, dwarfism deafness retinitis pigmentosa, dwarfism lethal type advanced bone age, dwarfism thin bones multiple fractures, dysmorphism cleft palate loose skin, Eagle syndrome, ectrodactyly cardiopathy dysmorphism, Elliott ludman Teebi syndrome, enamel hypoplasia cataract hydrocephaly, encephalocele anencephaly, enchondromatosis dwarfism deafness, Engelhard Yatziv syndrome, enlarged vestibular aqueduct syndrome, epidermal nevus vitamin D resistant rickets, epimetaphyseal dysplasia cataract, epiphyseal dysplasia dysmorphism camptodactyly, esophageal atresia coloboma talipes, extrasystoles short stature hyperpigmentation microcephaly, facial clefting corpus callosum agenesis, facio digito genital syndrome recessive form, facio skeletal genital syndrome rippberger type, familial capillaro-venous leptomeningeal angiomatosis, Dursun syndrome, Faye-Petersen-Ward-Carey syndrome, feigenbaum Bergeron syndrome, Feingold trainer syndrome, fetal brain disruption sequence, fetal enterovirus syndrome, fetal parainfluenza virus type 3 syndrome, fetal phenothiazine syndrome, fibromatosis multiple non ossifying, fibula aplasia complex brachydactyly, fibular hypoplasia scapulo pelvic dysplasia absent, Fitz-Hugh-Curtis syndrome, focal alopecia congenital megalencephaly, focal or multifocal malformations in neuronal migration, foix chavany Marie syndrome, Fontaine farriaux blanckaert syndrome, Fraser Jequier Chen syndrome, Freiberg disease, Friedman Goodman syndrome, frontonasal malformation cloacal exstrophy, frontonasal dysplasia Klippel feil syndrome, frontonasal dysplasia phocomelic upper limbs, Fryns Fabry Remans syndrome, Fryns Smeets Thiry syndrome, Fuchs atrophia gyrata chorioideae et retinae, Fukuda-Miyanomae-Nakata syndrome, Fuqua Berkovitz syndrome, Garret-Tripp syndrome, gas bloat syndrome, Gaucher ichthyosis restrictive dermopathy, gershinibaruch Leibo syndrome, Ghose-Sachdev-Kumar syndrome, gigantism advanced bone age hoarse cry, glossopalatine ankylosis micrognathia ear anomalies, goldstein hutt syndrome, goniodysgenesis intellectual disability short stature, green sandford davison syndrome, grix Blankenship Peterson syndrome, Ho-Kaufman-McAlister syndrome, Jaffer-Beighton syndrome, Judge Misch wright syndrome, Kashani-Strom-Utley syndrome, Kasznica-Carlson-Coppedge syndrome, Katsantoni-Papadakou-Lagoyanni syndrome, Kocher-debre-Semelaigne syndrome, Koone-Rizzo-Elias syndrome, Kozlowski Brown Hardwick syndrome, Kozlowski Ouvrier syndrome, Kozlowski Rafinski Klicharska syndrome, Kozlowski Warren Fisher syndrome, Krauss Herman Holmes syndrome, Krieble Bixler syndrome, Kuster Majewski Hammerstein syndrome, Kuster syndrome, Laugier-Hunziker syndrome, Laurence-Prosser-Rocker syndrome, le Marec-Bracq-Picaud syndrome, levator syndrome, Marinesco-Sjogren-like syndrome, Milner-Khallouf-Gibson syndrome, radio-digito-facial dysplasia, Seckel like syndrome majoor-krakauer type, neonatal aspiration syndrome, muscular fibrosis multifocal obstructed vessels, short stature contractures hypotonia, Alice in Wonderland syndrome, megacystis-microcolon-intestinal hypoperistalsis syndrome, Basilicata-Akhtar syndrome, Liberfarb syndrome, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardiac, facial, and digital anomalies with developmental delay, fibrosis, neurodegeneration, and cerebral angiomatosis, Duane anomaly-myopathy-scoliosis syndrome, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, acute radiation syndrome, monoclonal mast cell activation syndrome, oculocerebrodental syndrome, syndromic congenital sodium diarrhea, congenital brachyesophagus-intrathoracic stomach-vertebral anomalies syndrome, intellectual disability-cardiac anomalies-short stature-joint laxity syndrome, intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome, frontonasal dysplasia-bifid nose-upper limb anomalies syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, diaphragmatic hernia-short bowel-asplenia syndrome, warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome, Cramp-fasciculation syndrome, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, blepharophimosis-intellectual disability syndrome/genitopatellar overlap syndrome, CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome, cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome, KLHL7-related Bohring-Opitz-like syndrome, KLHL7-related cold-induced sweating-like syndrome, KAT6B-related multiple congenital anomalies syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, Ruzicka-Goerz-Anton syndrome, Sammartino-Decreccio syndrome, Samson-Gardner syndrome, Samson-Viljoen syndrome, Sanderson-Fraser syndrome, Sandhaus-Ben-Ami syndrome, prostatic malacoplakia associated with prostatic abscess, Saul-Wilkes-Stevenson syndrome, macrogyria, pseudobulbar palsy and intellectual disability, Schwartz-Cohen-addad-Lambert syndrome, Schlegelberger-Grote syndrome, Schrander-stumpel-Theunissen-Hulsmans syndrome, Saal-Bulas syndrome, Sackey-Sakati-Aur syndrome, Slti-Salem syndrome, Zerres Rietschel Majewski syndrome, Zazam Sheriff Phillips syndrome, Zadik-Barak-Levin syndrome, weinstein kliman scully syndrome, thickened earlobes with conductive deafness from incus-stapes abnormalities, ichthyosis linearis circumflexa, infantile striato thalamic degeneration, Landy-Donnai syndrome, merlob grunebaum reisner syndrome, Pavone Fiumara Rizzo syndrome, pfeiffer rockelein syndrome, Pfeiffer Tietze Welte syndrome, phosphoribosylpyrophosphate synthetase deficiency, piepkorn karp hickok syndrome, podder-tolmie syndrome, pointer syndrome, richieri-costa guion-almeida cohen syndrome, Rubinstein Taybi like syndrome, ruvalcaba churesigaew myhre syndrome, short limb dwarf lethal colavita kozlowski type, Mallory-Weiss syndrome, superior vena cava syndrome, piriformis syndrome, engraftment syndrome, Adams-Stokes syndrome, Leriche syndrome, multiple organ dysfunction syndrome, posterior leukoencephalopathy syndrome, cardio-renal syndrome, Rahman syndrome, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, Lopes-Maciel-Rodan syndrome, Stankiewicz-Isidor syndrome, Skraban-Deardorff syndrome, joint laxity, short stature, and myopia, Sweeney-Cox syndrome, Alkuraya-Kucinskas syndrome, Jaberi-Elahi syndrome, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, hearing impairment and infertile male syndrome, cardiocutaneous syndrome, neonatal diabetes, congenital sensorineural hearing loss and congenital cataracts, cardioectodermal syndrome, cannabinoid hyperemesis syndrome, retrograde cricopharyngeus dysfunction, Zinner syndrome, retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome, IFAP syndrome, DICER1-related tumor predisposition, Roberts-SC phocomelia syndrome, carcinoid syndrome, Bonnevie-Ullrich syndrome, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, RNU4ATAC spectrum disorder, syndromic congenital heart disease, hand-foot syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, gastrointestinal defects and immunodeficiency syndrome 1, achalasia-alacrima syndrome, black locks with albinism and deafness syndrome, Birt-Hogg-Dube syndrome, trigeminal trophic syndrome, developmental and/or epileptic encephalopathy with spike-wave activation in sleep, syndromic microspherophakia, painful legs and moving toes syndrome, congenital aphakia-iris hypoplasia-microphthalmia-microcornea syndrome, hereditary persistence of fetal hemoglobin-intellectual disability syndrome, developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome, primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome, post-cardiac arrest syndrome, early-onset obesity-hyperphagia-severe developmental delay syndrome, hereditary alpha tryptasemia syndrome, KINSSHIP syndrome, developmental delay, hypotrophy, and dysmorphic features without moebius syndrome, breast implant illness, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, craniosynostosis-facial dysmorphism-chiari-1 malformation-developmental and language delay syndrome, MYT1L-related developmental delay-intellectual disability-obesity syndrome, Houge-Janssens syndrome, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, pyoderma gangrenosum-acne-hidradenitis suppurativa-ankylosing spondylitis syndrome, psoriatic arthritis-pyoderma gangrenosum-acne-hidradenitis suppurativa syndrome, megalencephaly-polydactyly syndrome, Leigh syndrome, mitochondrial, auroneurodental syndrome, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, Grisel syndrome, arterial tortuosity-bone fragility syndrome, dialysis disequilibrium syndrome, brain abnormalities-severe developmental delay-facial dysmorphism-intellectual disability syndrome due to MEF2C mutation, Kariminejad neurodevelopmental syndrome, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, Morimoto-Ryu-Malicdan neuromuscular syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, Pan-Chung-Bellen syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, Tayoun-Maawali syndrome, ragopathy, cardiovascular-kidney-metabolic syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Li-Takada-Miyake syndrome, Guillouet-Gordon syndrome, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, RAC2-related combined immunodeficiency-bronchiectasis-cancer-predisposing syndrome, oculovertebral syndrome, Alsahan-Harris syndrome, Ververi-Brady syndrome, Dursun-Ozgul neurodevelopmental syndrome, immune dysregulation, neurodevelopmental defects, and colitis, Harel-Tora neurodevelopmental syndrome, Valence-Farazi cerebellar ataxia syndrome, dyschromatosis, ichthyosis, deafness, and atopic disease, Ramond-Elliott neurodevelopmental syndrome, STAD syndrome, craniosynostosis-scoliosis syndrome, loin pain hematuria syndrome, IRF6-related condition, linkeropathy, NDUFB11-related disorders, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy, antiphospholipid syndrome

Genetics & variants

GWAS landscape

223 GWAS associations across 15 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs94015934e-35MIR2113 - EIF4EBP2P3A
rs132176191e-27ZSCAN31?
rs42989678e-20CACNA1C, CACNA1C-IT3?
rs121541934e-18MMS22L - MIR2113C
rs98349702e-17HSPD1P6 - LINC02033?
rs121295735e-17RN7SKP19 - LINC01360?
rs44811505e-17ITIH3?
rs126584512e-16NIHCOLE - RNU6-334P?
rs17022943e-16MIR137HG?
rs70851043e-16BORCS7-ASMT?
rs17273023e-16PITPNM2?0.03
rs75311181e-15LINC02796?
rs41295852e-15TSNARE1?
rs7783713e-15SNORC?0.03
rs16195616e-15PITPNM2C
rs618672938e-15SORCS3?
rs116887672e-14EIF2S2P7 - ACTG1P22?
rs108838323e-14NT5C2?
rs713954555e-14ZSCAN2-AS1, ZSCAN2?
rs57582655e-14L3MBTL2-AS1, L3MBTL2?
rs30017237e-14PTPRF?
rs126688481e-13MAD1L1?
rs101494705e-13RNU7-160P - BAG5?
rs116935281e-12FTCDNL1 - RN7SL717P?
rs129580481e-12TCF4?
rs74054041e-12TMF1P1 - ERCC4?
rs23883341e-12MIR2113 - EIF4EBP2P3?0.03
rs1405059382e-12RPL6P31 - VPS45?
rs49063643e-12PPP1R13B?
rs803184424e-12RPL10AP3 - LINC01288?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90016616Peyrot WJ2021170,7564,819Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST90016624Peyrot WJ202140,6754,819Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST90016609Peyrot WJ202120,3524,819Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST90016598Peyrot WJ202119,0994,819Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST009600Cross-Disorder Group of the Psychiatric Genomics Consortium201919,009494,162Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders.
GCST90016603Peyrot WJ202118,3814,819Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST90016601Peyrot WJ202116,9924,819Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST90295972Tsetsos F20236,13313,565Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome.
GCST90455650Chen D20244,8199,488Unraveling shared susceptibility loci and Mendelian genetic associations linking educational attainment with multiple neuropsychiatric disorders.
GCST008907Mufford M20194,6448,695Concordance of genetic variation that increases risk for tourette syndrome and that influences its underlying neurocircuitry.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR2
Tier 3: regulatory2
Tier 4: intronic/intergenic46

MAF distribution

BucketVariants
common (>=0.05)50
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant42
intergenic_variant4
regulatory_region_variant2
3_prime_UTR_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs9401593698101925A>C,G,T0.05intron_variantMIR2113 - EIF4EBP2P34e-35Tier 4: intronic/intergenic
rs13217619628338894T>C0.05intron_variantZSCAN311e-27Tier 4: intronic/intergenic
rs4298967122299028A>C,G,T0.05intron_variantCACNA1C, CACNA1C-IT38e-20Tier 4: intronic/intergenic
rs12154193697939400G>A,C,T0.05intron_variantMMS22L - MIR21134e-18Tier 4: intronic/intergenic
rs9834970336814539T>C0.05regulatory_region_variantHSPD1P6 - LINC020332e-17Tier 3: regulatory
rs12129573173302683C>A0.05intron_variantRN7SKP19 - LINC013605e-17Tier 4: intronic/intergenic
rs4481150352803777T>C,G0.05intron_variantITIH35e-17Tier 4: intronic/intergenic
rs126584515104568336T>C0.05intron_variantNIHCOLE - RNU6-334P2e-16Tier 4: intronic/intergenic
rs1702294198036428T>A,C,G0.05intron_variantMIR137HG3e-16Tier 4: intronic/intergenic
rs708510410102869116A>G0.05intron_variantBORCS7-ASMT3e-16Tier 4: intronic/intergenic
rs172730212123148383G>A,C0.05intron_variantPITPNM23e-16Tier 4: intronic/intergenic
rs7531118172371556T>C0.05intron_variantLINC027961e-15Tier 4: intronic/intergenic
rs41295858142231572A>C,G,T0.05intron_variantTSNARE12e-15Tier 4: intronic/intergenic
rs7783712232878399A>C,G,T0.053_prime_UTR_variantSNORC3e-15Tier 2: splice/UTR
rs161956112123135721G>A,C,T0.05intron_variantPITPNM26e-15Tier 4: intronic/intergenic
rs6186729310104804166C>T0.05intron_variantSORCS38e-15Tier 4: intronic/intergenic
rs11688767257761059A>G,T0.05intron_variantEIF2S2P7 - ACTG1P222e-14Tier 4: intronic/intergenic
rs1088383210103111522T>A,G0.05intron_variantNT5C23e-14Tier 4: intronic/intergenic
rs713954551584610573A>C,G,T0.05intron_variantZSCAN2-AS1, ZSCAN25e-14Tier 4: intronic/intergenic
rs57582652241221893G>A,C,T0.05intron_variantL3MBTL2-AS1, L3MBTL25e-14Tier 4: intronic/intergenic
rs3001723143572014G>A0.05intron_variantPTPRF7e-14Tier 4: intronic/intergenic
rs1266884871981360G>A,T0.05intron_variantMAD1L11e-13Tier 4: intronic/intergenic
rs1014947014103551616A>G,T0.05regulatory_region_variantRNU7-160P - BAG55e-13Tier 3: regulatory
rs116935282199871784C>G,T0.05intron_variantFTCDNL1 - RN7SL717P1e-12Tier 4: intronic/intergenic
rs129580481855434367A>G,T0.05intron_variantTCF41e-12Tier 4: intronic/intergenic
rs74054041613656002T>A,C,G0.05intron_variantTMF1P1 - ERCC41e-12Tier 4: intronic/intergenic
rs2388334698143746A>G,T0.05intron_variantMIR2113 - EIF4EBP2P31e-12Tier 4: intronic/intergenic
rs1405059381150059494C>T0.05intron_variantRPL6P31 - VPS452e-12Tier 4: intronic/intergenic
rs490636414103748005C>G,T0.05intron_variantPPP1R13B3e-12Tier 4: intronic/intergenic
rs80318442834428027T>G0.05intergenic_variantRPL10AP3 - LINC012884e-12Tier 4: intronic/intergenic

ClinVar germline variants

100 retrieved; paginated sample, class counts are floors:

86 uncertain significance, 4 pathogenic, 3 likely benign, 2 likely risk allele, 2 conflicting classifications of pathogenicity, 1 benign, 1 likely pathogenic, 1 benign/likely benign

ClinVarVariant (HGVS)GeneClassificationReview
14912NM_002112.4(HDC):c.951G>A (p.Trp317Ter)HDCPathogenicno assertion criteria provided
4277990NM_002112.4(HDC):c.1140+1G>CHDCPathogeniccriteria provided, single submitter
1578NM_001281503.2(SLITRK1):c.1264del (p.Leu422fs)SLITRK1Pathogenicno assertion criteria provided
1579NM_001281503.2(SLITRK1):c.*689G>ASLITRK1Pathogenicno assertion criteria provided
3067887NM_002112.4(HDC):c.32-2A>GHDCLikely pathogeniccriteria provided, single submitter
1344622NM_001407.3(CELSR3):c.7853C>T (p.Ala2618Val)CELSR3Likely risk alleleno assertion criteria provided
1344624NM_001407.3(CELSR3):c.8765G>A (p.Arg2922His)CELSR3Likely risk alleleno assertion criteria provided
739922NM_001281503.2(SLITRK1):c.438C>A (p.Asp146Glu)SLITRK1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
786242NM_001281503.2(SLITRK1):c.1971C>G (p.Ser657=)SLITRK1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
2499585NM_001407.3(CELSR3):c.5634+1G>TCELSR3Uncertain significancecriteria provided, single submitter
1033484NM_002112.4(HDC):c.1511C>A (p.Thr504Lys)HDCUncertain significancecriteria provided, single submitter
1333882NM_002112.4(HDC):c.1568T>A (p.Ile523Asn)HDCUncertain significancecriteria provided, single submitter
3064496NM_002112.4(HDC):c.1133T>G (p.Val378Gly)HDCUncertain significancecriteria provided, single submitter
1334050NM_001281503.2(SLITRK1):c.341A>G (p.Asn114Ser)SLITRK1Uncertain significancecriteria provided, single submitter
312473NM_001281503.2(SLITRK1):c.*2203T>CSLITRK1Uncertain significancecriteria provided, single submitter
312474NM_001281503.2(SLITRK1):c.*2186T>ASLITRK1Uncertain significancecriteria provided, single submitter
312475NM_001281503.2(SLITRK1):c.*2087T>CSLITRK1Uncertain significancecriteria provided, single submitter
312478NM_001281503.2(SLITRK1):c.*1944A>GSLITRK1Uncertain significancecriteria provided, single submitter
312479NM_001281503.2(SLITRK1):c.*1882A>TSLITRK1Uncertain significancecriteria provided, single submitter
312480NM_001281503.2(SLITRK1):c.*1572C>GSLITRK1Uncertain significancecriteria provided, single submitter
312481NM_001281503.2(SLITRK1):c.*1313C>GSLITRK1Uncertain significancecriteria provided, single submitter
312485NM_001281503.2(SLITRK1):c.*1030G>ASLITRK1Uncertain significancecriteria provided, single submitter
312489NM_001281503.2(SLITRK1):c.*761G>ASLITRK1Uncertain significancecriteria provided, single submitter
312491NM_001281503.2(SLITRK1):c.*575C>TSLITRK1Uncertain significancecriteria provided, single submitter
312492NM_001281503.2(SLITRK1):c.*544C>ASLITRK1Uncertain significancecriteria provided, single submitter
312493NM_001281503.2(SLITRK1):c.*230T>GSLITRK1Uncertain significancecriteria provided, single submitter
312494NM_001281503.2(SLITRK1):c.*167C>GSLITRK1Uncertain significancecriteria provided, single submitter
312495NM_001281503.2(SLITRK1):c.*67G>ASLITRK1Uncertain significancecriteria provided, single submitter
312496NM_001281503.2(SLITRK1):c.*23G>ASLITRK1Uncertain significancecriteria provided, single submitter
312497NM_001281503.2(SLITRK1):c.2035A>C (p.Asn679His)SLITRK1Uncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 97 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

GeneHGNCEvidence routes
SOX5SOX5GWAS, Orphanet
FPR1FPR1GWAS, GenCC, Orphanet

GenCC gene–disease validity (cohort genes)

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

GeneClassificationInheritanceDiseaseRecords
ADAMTS6LimitedUnknownTourette syndrome
AGPAT5LimitedUnknownTourette syndrome
CNTN6LimitedUnknownTourette syndrome
CSNK1G3LimitedUnknownTourette syndrome
FAM120ALimitedUnknownTourette syndrome
FSCBLimitedUnknownTourette syndrome
GLIS3LimitedUnknownTourette syndrome7
HDCLimitedAutosomal dominantTourette syndrome2
HMGXB3LimitedUnknownTourette syndrome
PABPC5LimitedUnknownTourette syndrome
SLITRK1LimitedAutosomal dominantTourette syndrome4
SPRY2LimitedUnknownTourette syndrome3
TLN2LimitedUnknownTourette syndrome2
AADACNo Known Disease RelationshipUnknownTourette syndrome
ARL8ANo Known Disease RelationshipUnknownTourette syndrome
ATL2No Known Disease RelationshipUnknownTourette syndrome
CCDC7No Known Disease RelationshipUnknownTourette syndrome
CDK12No Known Disease RelationshipUnknownTourette syndrome
COL24A1No Known Disease RelationshipUnknownTourette syndrome
COLGALT2No Known Disease RelationshipUnknownTourette syndrome
CPEB3No Known Disease RelationshipUnknownTourette syndrome
DENND5ANo Known Disease RelationshipUnknownTourette syndrome6
FBXO15No Known Disease RelationshipUnknownTourette syndrome
FPR1No Known Disease RelationshipUnknownTourette syndrome2
GARIN4No Known Disease RelationshipUnknownTourette syndrome
GOPCNo Known Disease RelationshipUnknownTourette syndrome
HDAC5No Known Disease RelationshipUnknownTourette syndrome
HEPACAM2No Known Disease RelationshipUnknownTourette syndrome
KDM5BNo Known Disease RelationshipUnknownTourette syndrome5
KLHL9No Known Disease RelationshipUnknownTourette syndrome2

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SOX5Orphanet:31388412p12.1 microdeletion syndrome
SOX5Orphanet:313892Developmental and speech delay due to SOX5 deficiency
SOX5Orphanet:626Large/giant congenital melanocytic nevus
FPR1Orphanet:447740Aggressive periodontitis
UBAP1Orphanet:100993Autosomal dominant spastic paraplegia type 12
UBAP1Orphanet:631068Autosomal dominant spastic paraplegia type 80
WNT7BOrphanet:2470Matthew-Wood syndrome
GOPCOrphanet:171709Male infertility due to globozoospermia
KDM5BOrphanet:178469Autosomal dominant non-syndromic intellectual disability
KDM5BOrphanet:88616Autosomal recessive non-syndromic intellectual disability
KLHL9Orphanet:399081KLHL9-related early-onset distal myopathy
RFWD3Orphanet:84Fanconi anemia
GLIS3Orphanet:79118Neonatal diabetes-congenital hypothyroidism-congenital glaucoma-hepatic fibrosis-polycystic kidneys syndrome

Cohort genes → proteins

57 cohort genes, 57 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_and_gencc1
gwas_and_clinvar1
multi_evidence55

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SOX5HGNC:11201ENSG00000134532P35711Transcription factor SOX-5gwas,clinvar
SLITRK1HGNC:20297ENSG00000178235Q96PX8SLIT and NTRK-like protein 1gencc,clinvar
FPR1HGNC:3826ENSG00000171051P21462N-formyl peptide receptor 1gwas,gencc
HDCHGNC:4855ENSG00000140287P19113Histidine decarboxylasegencc,clinvar
SPRY2HGNC:11270ENSG00000136158O43597Protein sprouty homolog 2gencc
THBS3HGNC:11787ENSG00000169231P49746Thrombospondin-3gencc
TP53BP2HGNC:12000ENSG00000143514Q13625Apoptosis-stimulating of p53 protein 2gencc
UBAP1HGNC:12461ENSG00000165006Q9NZ09Ubiquitin-associated protein 1gencc
TPX2HGNC:1249ENSG00000088325Q9ULW0Targeting protein for Xklp2gencc
USP1HGNC:12607ENSG00000162607O94782Ubiquitin carboxyl-terminal hydrolase 1gencc
WNT7BHGNC:12787ENSG00000188064P56706Protein Wnt-7bgencc
ZNF112HGNC:12892ENSG00000062370Q9UJU3Zinc finger protein 112gencc
ZNF23HGNC:13023ENSG00000167377P17027Zinc finger protein 23gencc
ZNF37AHGNC:13102ENSG00000075407P17032Zinc finger protein 37Agencc
FAM120AHGNC:13247ENSG00000048828Q9NZB2Constitutive coactivator of PPAR-gamma-like protein 1gencc
FBXO15HGNC:13617ENSG00000141665Q8NCQ5F-box only protein 15gencc
PABPC5HGNC:13629ENSG00000174740Q96DU9Polyadenylate-binding protein 5gencc
HDAC5HGNC:14068ENSG00000108840Q9UQL6Histone deacetylase 5gencc
UNKLHGNC:14184ENSG00000059145Q9H9P5Putative E3 ubiquitin-protein ligase UNKLgencc
OR9I1HGNC:14718ENSG00000172377Q8NGQ6Olfactory receptor 9I1gencc
OR4M1HGNC:14735ENSG00000176299Q8NGD0Olfactory receptor 4M1gencc
TLN2HGNC:15447ENSG00000171914Q9Y4G6Talin-2gencc
SYNDIG1HGNC:15885ENSG00000101463Q9H7V2Synapse differentiation-inducing gene protein 1gencc
COLGALT2HGNC:16790ENSG00000198756Q8IYK4Procollagen galactosyltransferase 2gencc
AADACHGNC:17ENSG00000114771P22760Arylacetamide deacetylasegencc
ZNF385AHGNC:17521ENSG00000161642Q96PM9Zinc finger protein 385Agencc
GOPCHGNC:17643ENSG00000047932Q9HD26Golgi-associated PDZ and coiled-coil motif-containing proteingencc
KDM5BHGNC:18039ENSG00000117139Q9UGL1Lysine-specific demethylase 5Bgencc
TIGD2HGNC:18333ENSG00000180346Q4W5G0Tigger transposable element-derived protein 2gencc
KLHL9HGNC:18732ENSG00000198642Q9P2J3Kelch-like protein 9gencc
DENND5AHGNC:19344ENSG00000184014Q6IQ26DENN domain-containing protein 5Agencc
FSCBHGNC:20494ENSG00000189139Q5H9T9Fibrous sheath CABYR-binding proteingencc
COL24A1HGNC:20821ENSG00000171502Q17RW2Collagen alpha-1(XXIV) chaingencc
AGPAT5HGNC:20886ENSG00000155189Q9NUQ21-acyl-sn-glycerol-3-phosphate acyltransferase epsilongencc
CPEB3HGNC:21746ENSG00000107864Q8NE35Cytoplasmic polyadenylation element-binding protein 3gencc
CNTN6HGNC:2176ENSG00000134115Q9UQ52Contactin-6gencc
ADAMTS6HGNC:222ENSG00000049192Q9UKP5A disintegrin and metalloproteinase with thrombospondin motifs 6gencc
STRIP2HGNC:22209ENSG00000128578Q9ULQ0Striatin-interacting protein 2gencc
NLRP11HGNC:22945ENSG00000179873P59045NACHT, LRR and PYD domains-containing protein 11gencc
PLPP6HGNC:23682ENSG00000205808Q8IY26Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6gencc
ATL2HGNC:24047ENSG00000119787Q8NHH9Atlastin-2gencc
CDK12HGNC:24224ENSG00000167258Q9NYV4Cyclin-dependent kinase 12gencc
CSNK1G3HGNC:2456ENSG00000151292Q9Y6M4Casein kinase I isoform gamma-3gencc
ARL8AHGNC:25192ENSG00000143862Q96BM9ADP-ribosylation factor-like protein 8Agencc
POM121L12HGNC:25369ENSG00000221900Q8N7R1POM121-like protein 12gencc
RFWD3HGNC:25539ENSG00000168411Q6PCD5E3 ubiquitin-protein ligase RFWD3gencc
NMRK1HGNC:26057ENSG00000106733Q9NWW6Nicotinamide riboside kinase 1gencc
CCDC7HGNC:26533ENSG00000216937Q96M83Coiled-coil domain-containing protein 7gencc
GARIN4HGNC:26541ENSG00000162771Q8IYT1Golgi-associated RAB2 interactor protein 4gencc
HEPACAM2HGNC:27364ENSG00000188175A8MVW5HEPACAM family member 2gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SOX5Transcription factor SOX-5Transcription factor involved in chondrocytes differentiation and cartilage formation.
SLITRK1SLIT and NTRK-like protein 1It is involved in synaptogenesis and promotes excitatory synapse differentiation.
FPR1N-formyl peptide receptor 1Pattern recognition G-protein coupled receptor (PRR/GPCR) involved in innate recognition of N-formyl-methionyl peptides derived from invading microbes and host mitochondria as pathogen- and damage-associated molecular patterns (PAMPs and D…
HDCHistidine decarboxylaseCatalyzes the biosynthesis of histamine from histidine.
SPRY2Protein sprouty homolog 2Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2.
THBS3Thrombospondin-3Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions.
TP53BP2Apoptosis-stimulating of p53 protein 2Regulator that plays a central role in regulation of apoptosis and cell growth via its interactions with proteins such as TP53.
UBAP1Ubiquitin-associated protein 1Component of the ESCRT-I complex, a regulator of vesicular trafficking process.
TPX2Targeting protein for Xklp2Spindle assembly factor required for normal assembly of mitotic spindles.
USP1Ubiquitin carboxyl-terminal hydrolase 1Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2.
WNT7BProtein Wnt-7bLigand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.
ZNF112Zinc finger protein 112May be involved in transcriptional regulation.
ZNF23Zinc finger protein 23May be involved in transcriptional regulation.
ZNF37AZinc finger protein 37AMay be involved in transcriptional regulation.
FAM120AConstitutive coactivator of PPAR-gamma-like protein 1Component of the oxidative stress-induced survival signaling.
FBXO15F-box only protein 15Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
PABPC5Polyadenylate-binding protein 5Binds the poly(A) tail of mRNA.
HDAC5Histone deacetylase 5Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
UNKLPutative E3 ubiquitin-protein ligase UNKLMay participate in a protein complex showing an E3 ligase activity regulated by RAC1.
OR9I1Olfactory receptor 9I1Odorant receptor.
OR4M1Olfactory receptor 4M1Olfactory receptor that acts as a receptor of Asprosin hormone, potentially at the surface of hepatocytes and may help to promote hepatocyte glucose release.
TLN2Talin-2As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion.
SYNDIG1Synapse differentiation-inducing gene protein 1May regulate AMPA receptor content at nascent synapses, and have a role in postsynaptic development and maturation.
COLGALT2Procollagen galactosyltransferase 2Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of collagen.
AADACArylacetamide deacetylaseDisplays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly.
ZNF385AZinc finger protein 385ARNA-binding protein that affects the localization and the translation of a subset of mRNA.
GOPCGolgi-associated PDZ and coiled-coil motif-containing proteinPlays a role in intracellular protein trafficking and degradation.
KDM5BLysine-specific demethylase 5BHistone demethylase that demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code.
KLHL9Kelch-like protein 9Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis.
DENND5ADENN domain-containing protein 5AGuanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B.
FSCBFibrous sheath CABYR-binding proteinMay be involved in the later stages of fibrous sheath biogenesis and spermatozoa capacitation.
COL24A1Collagen alpha-1(XXIV) chainMay participate in regulating type I collagen fibrillogenesis at specific anatomical locations during fetal development.
AGPAT51-acyl-sn-glycerol-3-phosphate acyltransferase epsilonConverts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.
CPEB3Cytoplasmic polyadenylation element-binding protein 3Sequence-specific RNA-binding protein which acts as a translational repressor in the basal unstimulated state but, following neuronal stimulation, acts as a translational activator.
CNTN6Contactin-6Contactins mediate cell surface interactions during nervous system development.
STRIP2Striatin-interacting protein 2Plays a role in the regulation of cell morphology and cytoskeletal organization.
NLRP11NACHT, LRR and PYD domains-containing protein 11Involved in inflammation.
PLPP6Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6Magnesium-independent polyisoprenoid diphosphatase that catalyzes the sequential dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates.
ATL2Atlastin-2Atlastin-2 (ATL2) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network.
CDK12Cyclin-dependent kinase 12Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation.
CSNK1G3Casein kinase I isoform gamma-3Serine/threonine-protein kinase.
ARL8AADP-ribosylation factor-like protein 8APlays a role in lysosome motility.
RFWD3E3 ubiquitin-protein ligase RFWD3E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage.
NMRK1Nicotinamide riboside kinase 1Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN).
CCDC7Coiled-coil domain-containing protein 7May play a role in tumorigenesis.
GARIN4Golgi-associated RAB2 interactor protein 4RAB2B effector protein required for the compacted Golgi morphology, probably through interaction with small GTPase RAB2B.
HEPACAM2HEPACAM family member 2Required during prometaphase for centrosome maturation.
ZNF799Zinc finger protein 799May be involved in transcriptional regulation.
GLIS3Zinc finger protein GLIS3Acts both as a repressor and an activator of transcription.
RICTORRapamycin-insensitive companion of mTORComponent of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output.

Protein-family classification

Druggable: 13 · Difficult: 14 · Unknown: 30 · Druggable fraction: 0.23

Family distribution

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

FamilyGenesFoldFDR
Transcription factor111.6×0.623
Protease21.3×0.733
GPCR31.3×0.733
Antibody/Immunoglobulin21.0×0.733
Kinase21.0×0.733
Other/Unknown300.9×0.733
Scaffold/PPI30.9×0.733
Enzyme (other)40.8×0.733

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SOX5Transcription factornoHMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
SLITRK1Other/UnknownnoCys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
FPR1GPCRyes3.1.4.4GPCR_Rhodpsn, Formyl_rcpt-rel, GPCR_Rhodpsn_7TM
HDCEnzyme (other)yes4.1.1.22PyrdxlP-dep_de-COase, Aromatic_deC, PyrdxlP-dep_Trfase_major
SPRY2Other/UnknownnoSprouty, Sprouty_domain
THBS3Other/UnknownnoEGF, EGF-like_Ca-bd_dom, Thrombospondin_3-like_rpt
TP53BP2Scaffold/PPInoSH3_domain, Ankyrin_rpt, Ubiquitin-like_domsf
UBAP1Other/UnknownnoUBA-like_sf, UBA, UMA
TPX2Other/UnknownnoTPX2_fam, Aurora-A-bd, TPX2_C
USP1ProteaseyesPeptidase_C19_UCH, USP_CS, USP
WNT7BOther/UnknownnoWnt, Wnt7, Wnt_CS
ZNF112Transcription factornoKRAB, Znf_C2H2_type, KRAB_dom_sf
ZNF23Transcription factornoKRAB, Znf_C2H2_type, Znf_C2H2_sf
ZNF37ATranscription factornoKRAB, Znf_C2H2_type, KRAB_dom_sf
FAM120AOther/UnknownnoCoact_PPARg, PIN-like_dom_sf
FBXO15Other/UnknownnoF-box_dom, F-box-like_dom_sf
PABPC5Other/UnknownnoRRM_dom, RRM_euk-type, PABP_1234
HDAC5Other/UnknownnoHDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
UNKLTranscription factornoZnf_CCCH, Znf_RING, Znf_RING/FYVE/PHD
OR9I1GPCRyesGPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
OR4M1GPCRyesGPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
TLN2Other/UnknownnoFERM_domain, IRS_PTB, ILWEQ_dom
SYNDIG1Other/UnknownnoCD225/Dispanin_fam
COLGALT2Enzyme (other)yes2.4.1.50Glyco_trans_25, Nucleotide-diphossugar_trans, Collagen_mod_GT25
AADACOther/UnknownnoAB_hydrolase_3, Arylacetamide_deacetylase, AB_hydrolase_fold
ZNF385ATranscription factornoMatrin/U1-like-C_Znf_C2H2, Znf_C2H2_type, Znf_C2H2_sf
GOPCScaffold/PPInoPDZ, PDZ_sf, GOPC
KDM5BTranscription factorno1.14.11.67ARID_dom, Znf_PHD, JmjC_dom
TIGD2Transcription factornoDDE_SF_endonuclease_dom, HTH_CenpB_DNA-bd_dom, HTH_Psq
KLHL9Other/UnknownnoBTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf
DENND5AOther/UnknownnoPLAT/LH2_dom, cDENN_dom, Run_dom
FSCBOther/UnknownnoFSCB
COL24A1Other/UnknownnoFib_collagen_C, Collagen, ConA-like_dom_sf
AGPAT5Enzyme (other)yes2.3.1.51Plipid/glycerol_acylTrfase, Acyltransf_C
CPEB3Other/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, CEBP_ZZ
CNTN6Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, FN3_dom
ADAMTS6ProteaseyesTSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
STRIP2Other/UnknownnoFar11/STRP_N, Far11/STRP_C, Far11/STRP
NLRP11Other/UnknownnoLeu-rich_rpt, DAPIN, NACHT_NTPase
PLPP6Other/UnknownnoPAP2/HPO, PAP2/HPO_sf
ATL2Other/UnknownnoGuanylate-bd/ATL_C, Guanylate-bd_N, P-loop_NTPase
CDK12Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CSNK1G3Kinaseyes2.7.11.1Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ARL8AOther/UnknownnoSmall_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase
POM121L12Other/Unknownno
RFWD3Transcription factornoWD40_rpt, Znf_RING, Znf_RING/FYVE/PHD
NMRK1Enzyme (other)yes2.7.1.173P-loop_NTPase
CCDC7Other/UnknownnoCCDC7
GARIN4Other/UnknownnoGARIL-like_Rab2B-bd
HEPACAM2Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)1
moderate (6-20)3
broad (>20)53
unknown0

Top tissues across cohort

TissueCohort genes
secondary oocyte9
cortical plate7
oocyte7
male germ line stem cell (sensu Vertebrata) in testis7
calcaneal tendon6
tibia6
sperm6
ventricular zone5
buccal mucosa cell5
left testis5
right uterine tube4
parotid gland4
sural nerve4
C1 segment of cervical spinal cord4
corpus callosum4
Brodmann (1909) area 233
lower esophagus mucosa3
primordial germ cell in gonad3
prefrontal cortex2
monocyte2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SOX5221ubiquitousmarkercortical plate, calcaneal tendon, synovial joint
SLITRK186broadmarkerBrodmann (1909) area 46, prefrontal cortex, Brodmann (1909) area 23
FPR1215broadmarkerblood, monocyte, leukocyte
HDC178tissue_specificmarkergall bladder, oocyte, secondary oocyte
SPRY2281ubiquitousmarkercartilage tissue, tibial nerve, right hemisphere of cerebellum
THBS3232ubiquitousmarkerright uterine tube, tibia, body of uterus
TP53BP2283ubiquitousmarkerventricular zone, ganglionic eminence, caudate nucleus
UBAP1288ubiquitousmarkerlower esophagus mucosa, gastrocnemius, muscle of leg
TPX2200ubiquitousmarkerventricular zone, ganglionic eminence, embryo
USP1293ubiquitousmarkersecondary oocyte, ventricular zone, sperm
WNT7B122broadmarkervena cava, buccal mucosa cell, parotid gland
ZNF112248ubiquitousyesgerminal epithelium of ovary, cortical plate, male germ line stem cell (sensu Vertebrata) in testis
ZNF23134ubiquitousyescortical plate, primordial germ cell in gonad, pituitary gland
ZNF37A256ubiquitousmarkerparotid gland, visceral pleura, parietal pleura
FAM120A304ubiquitousmarkertibia, mucosa of sigmoid colon, visceral pleura
FBXO15197broadmarkerbronchial epithelial cell, bronchus, right uterine tube
PABPC5157broadyesadrenal tissue, calcaneal tendon, right adrenal gland cortex
HDAC5240ubiquitousmarkercortical plate, lower esophagus mucosa, skin of leg
UNKL259ubiquitousyessecondary oocyte, oocyte, sural nerve
OR9I10markercolonic epithelium, ventricular zone, cortical plate
OR4M16markermale germ line stem cell (sensu Vertebrata) in testis, sural nerve, right testis
TLN2257ubiquitousmarkersural nerve, middle temporal gyrus, frontal pole
SYNDIG1206broadmarkerC1 segment of cervical spinal cord, spinal cord, prefrontal cortex
COLGALT2242broadmarkertibia, corpus callosum, C1 segment of cervical spinal cord
AADAC164tissue_specificmarkerjejunal mucosa, right adrenal gland, right adrenal gland cortex
ZNF385A243ubiquitousmarkerskin of leg, skin of abdomen, monocyte
GOPC261ubiquitousmarkertibia, epithelial cell of pancreas, parietal pleura
KDM5B272ubiquitousmarkersperm, male germ cell, left testis
TIGD2223ubiquitousyesamniotic fluid, primordial germ cell in gonad, pigmented layer of retina
KLHL9294ubiquitousmarkercorpus epididymis, mucosa of paranasal sinus, choroid plexus epithelium

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

SymbolInteractor count
RICTOR4,055
KDM5B3,722
HDAC53,462
TPX23,219
GOPC2,950
CDK122,938
USP12,504
HDC2,424
SOX52,310
SLITRK12,283

Intra-cohort edges

ABSources
AADACFSCBstring_interaction
ADAMTS6LCN12string_interaction
ADAMTS6PPWD1string_interaction
ATL2FAM120Abiogrid_interaction
ATL2FPR1biogrid_interaction
HDCSLITRK1string_interaction

Structural data

PDB: 21 · AlphaFold-only: 36 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
KDM5BQ9UGL156
CDK12Q9NYV439
GOPCQ9HD2635
RICTORQ6R32716
USP1O9478215
TPX2Q9ULW014
CSNK1G3Q9Y6M410
NMRK1Q9NWW67
TP53BP2Q136256
CPEB3Q8NE356
FPR1P214625
SPRY2O435975
PPWD1Q96BP35
HDCP191134
UBAP1Q9NZ093
ARL8AQ96BM93
SLITRK1Q96PX82
HDAC5Q9UQL62
LYPD6Q86Y782
TLN2Q9Y4G61
RFWD3Q6PCD51

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
AADACP2276095.64
AGPAT5Q9NUQ294.23
KLHL9Q9P2J392.00
PABPC5Q96DU991.44
WNT7BP5670690.71
OR4M1Q8NGD089.70
OR9I1Q8NGQ689.57
COLGALT2Q8IYK488.44
LCN12Q6JVE586.62
CNTN6Q9UQ5286.19
THBS3P4974685.66
NLRP11P5904585.34
ATL2Q8NHH984.36
STRIP2Q9ULQ079.68
HEPACAM2A8MVW578.76
DENND5AQ6IQ2677.74
ADAMTS6Q9UKP577.45
FBXO15Q8NCQ577.42
TIGD2Q4W5G075.05
PLPP6Q8IY2673.75
ZNF23P1702772.27
ZNF799Q96GE570.87
FAM120AQ9NZB268.66
UNKLQ9H9P567.86
ZNF37AP1703264.29
HMGXB3Q1276664.21
ZNF385AQ96PM962.73
SOX5P3571158.95
ZNF112Q9UJU355.13
SYNDIG1Q9H7V253.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 510. Enrichment computed across 250 evidence-associated genes (142 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 142 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
TP53 Regulates Transcription of Death Receptors and Ligands320.1×0.105TP53BP2, PPP1R13B, TMEM219
Regulation of TP53 Activity through Association with Co-factors317.2×0.105TP53BP2, PPP1R13B, ZNF385A
Generic Transcription Pathway212.2×0.105TFAP2B, TP53BP2, ZNF112, ZNF23, ZNF37A, ZKSCAN3, PPP1R13B, TFAP2D (+13 more)
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors313.4×0.171TFAP2B, TFAP2D, KDM5B
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors223.0×0.280CHRNA3, CHRNB4
Highly calcium permeable nicotinic acetylcholine receptors217.9×0.280CHRNA3, CHRNB4
Activation of PUMA and translocation to mitochondria216.1×0.280TP53BP2, PPP1R13B
Signaling by FGFR3216.1×0.280BRAF, SPRY2
Negative regulation of activity of TFAP2 (AP-2) family transcription factors216.1×0.280TFAP2B, TFAP2D
Role of second messengers in netrin-1 signaling214.6×0.280TRPC4, DCC
Signaling by FGFR4214.6×0.280BRAF, SPRY2
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors214.6×0.280CHRNA3, CHRNB4
Presynaptic nicotinic acetylcholine receptors213.4×0.280CHRNA3, CHRNB4
Activation of the TFAP2 (AP-2) family of transcription factors213.4×0.280TFAP2B, TFAP2D
Budding and maturation of HIV virion38.6×0.280UBAP1, CHMP2B, VPS37B
Endosomal Sorting Complex Required For Transport (ESCRT)37.8×0.280UBAP1, CHMP2B, VPS37B
Late endosomal microautophagy36.9×0.280UBAP1, CHMP2B, VPS37B
Defective ALG8 causes CDG-1h180.4×0.294ALG8
Membrane binding and targetting of GAG proteins211.5×0.294UBAP1, VPS37B
Acetylcholine binding and downstream events211.5×0.294CHRNA3, CHRNB4
Signaling by FGFR1211.5×0.294BRAF, SPRY2
Postsynaptic nicotinic acetylcholine receptors211.5×0.294CHRNA3, CHRNB4
Phase 2 - plateau phase210.7×0.308CACNA1C, CACNB2
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain210.7×0.308TP53BP2, PPP1R13B
NCAM signaling for neurite out-growth35.7×0.309CACNA1C, CACNA1I, CACNB2
Spry regulation of FGF signaling210.1×0.322BRAF, SPRY2
RND3 GTPase cycle35.5×0.325TXNL1, PICALM, KCTD13
NCAM1 interactions35.2×0.353CACNA1C, CACNA1I, CACNB2
Diseases of glycosylation43.7×0.405MUC16, ADAMTS6, THSD7A, ALG8
HDMs demethylate histones34.8×0.410KDM3B, KDM5B, KDM4A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 225 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
obsolete L-histidine metabolic process174.9×0.217HDC
acylglycerol metabolic process174.9×0.217AGPAT5
specification of animal organ identity174.9×0.217TBR1
regulation of acetylcholine secretion, neurotransmission174.9×0.217CHRNA3
muscle cell migration174.9×0.217TCP11L2
regulation of cell projection size174.9×0.217WNT7B
isoquinoline alkaloid metabolic process174.9×0.217CYP2D6
chemoattraction of dopaminergic neuron axon174.9×0.217WNT7B
thyroid-stimulating hormone signaling pathway174.9×0.217TSHR
proton-transporting ATP synthase complex assembly174.9×0.217ATPAF2
negative regulation of nervous system development174.9×0.217ELAPOR2
lobar bronchus development174.9×0.217WNT7B
cerebellum vasculature development174.9×0.217IMMP2L
leukocyte adhesion to arterial endothelial cell174.9×0.217SLC39A8
olfactory bulb axon guidance174.9×0.217BCL11B
outer medullary collecting duct development174.9×0.217WNT7B
negative regulation of organofluorine metabolic process174.9×0.217CYP2D6
plasma membrane selenite transport174.9×0.217SLC39A8
hippocampal interneuron differentiation174.9×0.217LYPD6
regulation of superoxide dismutase activity174.9×0.217SZT2
regulation of receptor localization to synapse174.9×0.217NPTN
regulation of neuronal signal transduction174.9×0.217CLU
positive regulation of neurofibrillary tangle assembly174.9×0.217CLU
positive regulation of error-prone translesion synthesis174.9×0.217USP1
positive regulation of GTP binding174.9×0.217CLN5
cellular response to thyrotropin-releasing hormone174.9×0.217TSHR
positive regulation of clathrin coat assembly174.9×0.217HIP1R
negative regulation of blood vessel branching174.9×0.217CTNND1
mitochondrial manganese ion transmembrane transport174.9×0.217SLC39A8
regulation of estradiol secretion174.9×0.217KDM5B

Therapeutics

Drugs indicated for this disease

3 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AripiprazoleApproved (phase 4)
HaloperidolApproved (phase 4)
PimozideApproved (phase 4)
EcopipamPhase 3 (in late-stage trials)
GuanfacinePhase 3 (in late-stage trials)
NabiximolsPhase 3 (in late-stage trials)
PramipexolePhase 3 (in late-stage trials)
TiapridePhase 3 (in late-stage trials)
TopiramatePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine, Atomoxetine, Cannabidiol, Cannabinol, Dronabinol, Palmidrol, Risperidone, Tetrabenazine, Valbenazine.

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 7 · Phased (≥1): 9 · Undrugged: 48

Druggability breadth: 57 of 250 evidence-associated genes (23%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

SymbolExample approved molecule
FPR1PHENYLBUTAZONE
USP1PIMOZIDE
HDAC5CELECOXIB
AADACFLUTAMIDE
CSNK1G3NERATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
HDAC5304
CDK12173
CSNK1G3164
FPR1114
RICTOR52
USP144
TPX221
KDM5B23
AADAC14
SOX500

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PHENYLBUTAZONE4FPR1
MONTELUKAST SODIUM4FPR1
CINACALCET HYDROCHLORIDE4FPR1
PENICILLIN G POTASSIUM4FPR1
APREPITANT4FPR1
LOPERAMIDE HYDROCHLORIDE4FPR1
PERPHENAZINE4FPR1
SULFINPYRAZONE4FPR1
PIMOZIDE4USP1
TRIFLUOPERAZINE4USP1
CELECOXIB4HDAC5
PHENYLBUTANOIC ACID4HDAC5
SODIUM PHENYLBUTYRATE4HDAC5
ROMIDEPSIN4HDAC5
BELINOSTAT4HDAC5
PANOBINOSTAT4HDAC5
VORINOSTAT4HDAC5
GIVINOSTAT4HDAC5
BENDAMUSTINE4HDAC5
FLUTAMIDE4AADAC
NERATINIB4CSNK1G3
SUNITINIB4CSNK1G3
FLUPENTIXOL3USP1
CURCUMIN3HDAC5
CAFFEIC ACID3HDAC5, KDM5B
PRACINOSTAT3HDAC5
TACEDINALINE3HDAC5
ENTINOSTAT3HDAC5
TUCIDINOSTAT3HDAC5
ABEXINOSTAT3HDAC5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

SymbolAssaysType breakdown
HDAC51,686Binding:1670, ADMET:11, Functional:4, Toxicity:1
CDK12347Binding:341, Functional:6
CSNK1G3216Binding:215, Functional:1
KDM5B146Binding:146
FPR1138Functional:85, Binding:53
RICTOR99Binding:99
USP176Binding:71, Functional:5
TPX224Binding:24
AADAC20ADMET:19, Binding:1
GOPC10Binding:9, Functional:1
FAM120A2Binding:2
HDC1Binding:1
TP53BP21Binding:1
AGPAT51Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
FPR13.1.4.4phospholipase D
HDC4.1.1.22histidine decarboxylase
COLGALT22.4.1.50procollagen galactosyltransferase
KDM5B1.14.11.67[histone H3]-trimethyl-L-lysine4 demethylase
AGPAT52.3.1.511-acylglycerol-3-phosphate O-acyltransferase
CDK122.7.11.22, 2.7.11.23cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
CSNK1G32.7.11.1non-specific serine/threonine protein kinase
NMRK12.7.1.173, 2.7.1.22nicotinate riboside kinase, ribosylnicotinamide kinase
PPWD15.2.1.8peptidylprolyl isomerase

Cohort genes with high screening signal

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

SymbolChEMBL assays
FPR1138
HDAC51,686
KDM5B146
CDK12347
CSNK1G3216

Pharmacogenomics

Cohort genes with a PharmGKB record: 56; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

CompoundMax phaseCohort target (bioactivity)
PHENYLBUTAZONE4FPR1
MONTELUKAST SODIUM4FPR1
CINACALCET HYDROCHLORIDE4FPR1
PENICILLIN G POTASSIUM4FPR1
APREPITANT4FPR1
LOPERAMIDE HYDROCHLORIDE4FPR1
PERPHENAZINE4FPR1
SULFINPYRAZONE4FPR1
TRIFLUOPERAZINE4USP1
CELECOXIB4HDAC5
PHENYLBUTANOIC ACID4HDAC5
SODIUM PHENYLBUTYRATE4HDAC5
ROMIDEPSIN4HDAC5
BELINOSTAT4HDAC5
PANOBINOSTAT4HDAC5
VORINOSTAT4HDAC5
GIVINOSTAT4HDAC5
BENDAMUSTINE4HDAC5
FLUTAMIDE4AADAC
NERATINIB4CSNK1G3
SUNITINIB4CSNK1G3
FLUPENTIXOL3USP1
CURCUMIN3HDAC5
CAFFEIC ACID3HDAC5, KDM5B
PRACINOSTAT3HDAC5
TACEDINALINE3HDAC5
ENTINOSTAT3HDAC5
TUCIDINOSTAT3HDAC5
ABEXINOSTAT3HDAC5

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)5FPR1, USP1, HDAC5, AADAC, CSNK1G3
BPhased (≥1) drug, not yet approved4TPX2, KDM5B, CDK12, RICTOR
CDruggable family + PDB, no drug2HDC, NMRK1
DDruggable family + AlphaFold only, no drug7OR9I1, OR4M1, COLGALT2, AGPAT5, CNTN6, ADAMTS6, HEPACAM2
EDifficult family or no structure, no drug39SOX5, SLITRK1, SPRY2, THBS3, TP53BP2, UBAP1, WNT7B, ZNF112, ZNF23, ZNF37A (+29 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SOX50
SLITRK10
HDC1
SPRY20
THBS30
TP53BP21
UBAP10
WNT7B0
ZNF1120
ZNF230
ZNF37A0
FAM120A2
FBXO150
PABPC50
UNKL0
OR9I10
OR4M10
TLN20
SYNDIG10
COLGALT20
ZNF385A0
GOPC10
TIGD20
KLHL90
DENND5A0
FSCB0
COL24A10
AGPAT51
CPEB30
CNTN60

Clinical trials & evidence

Clinical trials

Clinical trials: 183.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified110
PHASE236
PHASE311
PHASE111
PHASE47
PHASE2/PHASE33
EARLY_PHASE13
PHASE1/PHASE22

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00152750PHASE4UNKNOWNStudy of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824PHASE4TERMINATEDSafety Study of Galantamine in Tic Disorders
NCT00241176PHASE4COMPLETEDOpen Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838PHASE4COMPLETEDComparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056PHASE4COMPLETEDDeveloping New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000PHASE4COMPLETEDGuanfacine in Children With Tic Disorders
NCT03239210PHASE4COMPLETEDEffects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT06021522PHASE3ACTIVE_NOT_RECRUITINGA Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004376PHASE3COMPLETEDPhase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323PHASE3COMPLETEDA Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336PHASE3COMPLETEDAn Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00218777PHASE2/PHASE3COMPLETEDCognitive Behavior Therapy and Habit Reversal Training for the Treatment of Chronic Tic Disorders in Children
NCT00478842PHASE3COMPLETEDPallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863PHASE3TERMINATEDOpen-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695PHASE3COMPLETEDPhase III Study of 5LGr to Treat Tic Disorder
NCT03087201PHASE3COMPLETEDCANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03452943PHASE2/PHASE3COMPLETEDAlternatives for Reducing Tics in Tourette Syndrome (TS): A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents
NCT03487783PHASE3COMPLETEDAripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291PHASE3TERMINATEDEvaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256PHASE3COMPLETEDA Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT03958617PHASE2/PHASE3COMPLETEDThalamic Deep Brain Stimulation for Tourette Syndrome
NCT05126888PHASE2NOT_YET_RECRUITINGSCI-110 in the Treatment of Tourette Syndrome
NCT06081348PHASE2RECRUITINGSertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06194305PHASE2RECRUITINGMultimodal Profiling of Response to Pediatric Comprehensive Behavioral Intervention for Tics
NCT06315751PHASE2ACTIVE_NOT_RECRUITINGEfficacy and Safety of Gemlapodect (NOE-105) in Adults and Adolescents With Tourette Syndrome
NCT06678737PHASE2RECRUITINGCBIT+TMS R33 Phase
NCT00004393PHASE2COMPLETEDPhase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652PHASE2COMPLETEDPhase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985PHASE2COMPLETEDEffectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909PHASE2COMPLETEDThalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308PHASE2COMPLETEDTranscranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467PHASE2COMPLETEDPramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549PHASE2TERMINATEDRepetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353PHASE2WITHDRAWNA Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01244633PHASE1/PHASE2COMPLETEDEcopipam Treatment of Tourette Syndrome
NCT01475383PHASE2WITHDRAWNStudy Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269PHASE2COMPLETEDA Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773PHASE2COMPLETEDSafety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698PHASE2COMPLETEDEcopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02112253PHASE1/PHASE2WITHDRAWNOptimising Anterior Pallidal Deep Brain Stimulation for Tourette’s Syndrome

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
VALBENAZINE412
ARIPIPRAZOLE43
GUANFACINE43
ONDANSETRON43
PERGOLIDE43
ATOMOXETINE42
CLONIDINE42
TOPIRAMATE42
CYCLOSERINE41
DEUTETRABENAZINE41
DRONABINOL41
GALANTAMINE41
LEVETIRACETAM41
PIMAVANSERIN41
PIMOZIDE41
RILUZOLE41
ECOPIPAM34
(D)-SERINE31
NABIXIMOLS31
PALMIDROL31
TIAPRIDE31
VATIQUINONE31
ELCUBRAGISTAT22
CLOPIMOZIDE21
ETIRACETAM21
GEMLAPODECT21
LEVCYCLOSERINE21
PF-0365474621
REDAFAMDASTAT21
SEPRANOLONE21