Takayasu arteritis

Summary

Takayasu arteritis (MONDO:0017991) is a disease with 75 cohort genes (166 GWAS associations across 10 studies) and 74 clinical trials. The dominant Reactome pathway is Interferon gamma signaling (9 cohort genes). Top therapeutic interventions include tofacitinib, adalimumab, and cravacitinib.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 75
• GWAS associations: 166
• Phenotypes (HPO): 54
• Clinical trials: 74

Clinical features

Epidemiology

Prevalence records

21 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.084	Europe	Validated
Point prevalence	1-9 / 100 000	1.34	Europe	Validated
Annual incidence	<1 / 1 000 000	0.06	United Kingdom	Validated
Annual incidence	1-9 / 1 000 000	0.1	Sweden	Validated
Annual incidence	<1 / 1 000 000	0.04	Denmark	Validated
Annual incidence	1-9 / 1 000 000	0.13	Lithuania	Validated
Annual incidence	1-9 / 1 000 000	0.22	Kuwait	Validated
Annual incidence	1-9 / 1 000 000	0.26	United States	Validated
Annual incidence	1-9 / 1 000 000	0.15	Norway	Validated
Annual incidence	1-9 / 1 000 000	0.24	Korea, Republic of	Validated
Annual incidence	<1 / 1 000 000	0.092	Poland	Validated
Point prevalence	1-9 / 100 000	4	Japan	Validated
Point prevalence	1-9 / 1 000 000	0.98	Sweden	Validated
Point prevalence	1-9 / 1 000 000	0.47	United Kingdom	Validated
Point prevalence	1-9 / 1 000 000	0.78	Kuwait	Validated
Point prevalence	1-9 / 100 000	2.56	Norway	Validated
Point prevalence	1-9 / 100 000	2.82	Korea, Republic of	Validated
Point prevalence	1-9 / 1 000 000	0.46	Poland	Validated
Point prevalence	1-9 / 100 000		Worldwide	Not yet validated
Annual incidence	<1 / 1 000 000	0.07	Germany	Not yet validated

Signs & symptoms

Clinical features (HPO)

54 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001654	Abnormal heart valve morphology	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002617	Dilatation	Very frequent (80-99%)
HP:0002633	Vasculitis	Very frequent (80-99%)
HP:0012089	Arteritis	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0100545	Arterial stenosis	Very frequent (80-99%)
HP:0100735	Hypertensive crisis	Very frequent (80-99%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0001646	Abnormal aortic valve morphology	Frequent (30-79%)
HP:0001658	Myocardial infarction	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001920	Renal artery stenosis	Frequent (30-79%)
HP:0002039	Anorexia	Frequent (30-79%)
HP:0002076	Migraine	Frequent (30-79%)
HP:0002092	Pulmonary arterial hypertension	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0003565	Elevated erythrocyte sedimentation rate	Frequent (30-79%)
HP:0004417	Intermittent claudication	Frequent (30-79%)
HP:0004970	Ascending tubular aorta aneurysm	Frequent (30-79%)
HP:0012649	Increased inflammatory response	Frequent (30-79%)
HP:0020141	Blood pressure substantially higher in legs than arms	Frequent (30-79%)
HP:0032554	Absent pulse	Frequent (30-79%)
HP:0100749	Chest pain	Frequent (30-79%)
HP:0100758	Gangrene	Frequent (30-79%)
HP:0200042	Skin ulcer	Frequent (30-79%)
HP:6000944	Carotidynia	Frequent (30-79%)
HP:6000945	Asymmetric blood pressure between arms	Frequent (30-79%)
HP:0000488	Retinopathy	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0001644	Dilated cardiomyopathy	Occasional (5-29%)
HP:0001659	Aortic regurgitation	Occasional (5-29%)
HP:0002094	Dyspnea	Occasional (5-29%)
HP:0002105	Hemoptysis	Occasional (5-29%)
HP:0002167	Abnormality of speech or vocalization	Occasional (5-29%)
HP:0002321	Vertigo	Occasional (5-29%)
HP:0002326	Transient ischemic attack	Occasional (5-29%)
HP:0002637	Cerebral ischemia	Occasional (5-29%)
HP:0002829	Arthralgia	Occasional (5-29%)
HP:0004306	Abnormality of the endocardium	Occasional (5-29%)
HP:0004372	Reduced consciousness/confusion	Occasional (5-29%)
HP:0005244	Gastrointestinal infarctions	Occasional (5-29%)
HP:0011227	Elevated circulating C-reactive protein concentration	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Takayasu arteritis
Mondo ID	MONDO:0017991
EFO	EFO:1001857
MeSH	D013625
OMIM	207600
Orphanet	3287, 99079
DOID	DOID:2508
ICD-10-CM	M31.4
ICD-11	1327645131
NCIT	C34391, C35062
SNOMED CT	239937004
UMLS	C0039263
MedGen	21458
GARD	0007730
MedDRA	10043097
NORD	806
Anatomy (UBERON)	UBERON:0004363
Is cancer (heuristic)	no

Also known as: aortic arch arteritis · aortic arch syndrome · Arteritis, Takayasu · cervical aortic arch · idiopathic aortitis · pharyngeal arch artery syndromic disease · TA · Takayasu arteritis · Takayasu disease · Takayasu’s arteritis · Takayasu’s disease

Data availability: 166 GWAS associations (10 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Takayasu arteritis

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, 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

166 GWAS associations across 10 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2844678	6e-47	NAPGP2 - MUC21	?	2.71
rs12524487	6e-38	MICA-AS1	?	3.12
HLA-B*5201	4e-36		?	4.37
rs117298325	4e-34	LINC02571 - HLA-B	C
rs9262437	5e-31	MUC21 - MUC22	?
rs17193507	7e-30	MICA-AS1	?	3.28
HLA-B*1302	3e-25		?	3.21
HLAB*5201	3e-20		?
rs61444472	2e-17	PSORS1C1	?
rs45479291	2e-16	HLA-V, HLA-V, HLA-F-AS1, HCG4	?
HLAB*1302	2e-16		?
HLA-B*1501	1e-15		?	3.07
rs2322599	3e-13	PTK2B	G	1.94
rs2836883	1e-12	LINC02940 - RPL23AP12	A	0.64
rs10919543	6e-12	RPS23P10 - FCGR3A	G	1.81
rs2099684	7e-12	HSPA6 - RPS23P10	C	1.54
rs1265067	8e-12	CCHCR1	?	2.41
rs62392216	1e-11	HLA-W, POLR1HASP, POLR1HASP	?
HLAB*1501	1e-11		?
rs9271066	2e-11	HLA-DRB1 - HLA-DQA1	?
rs3130618	2e-11	GPANK1	?	2.6
rs3130627	3e-11	PRRC2A	?	2.61
rs10573	3e-11	ABHD16A	?	2.6
rs1576	3e-11	CCHCR1	?	2.36
rs2517985	3e-11	CCHCR1	?	2.36
rs9267535	3e-11	LY6G5C	?	2.59
rs3134940	3e-11	AGER	?	2.52
rs9267532	3e-11	LY6G5B	?	2.61
rs1265078	3e-11	CCHCR1	?	2.36
rs3130070	4e-11	PRRC2A	?	2.57

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011938	Ortiz-Fernandez L	2020	683	1,721	Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.
GCST006575	Renauer PA	2015	516	0	Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study.
GCST006984	Terao C	2018	411	2,158	Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis.
GCST006863	Saruhan-Direskeneli G	2013	305	0	Identification of multiple genetic susceptibility loci in Takayasu arteritis.
GCST011939	Ortiz-Fernandez L	2020	286	2,652	Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.
GCST011937	Ortiz-Fernandez L	2020	229	1,088	Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.
GCST90137503	Liu L	2022	200	1,675	Whole Exome Sequencing Revealed Variants That Predict Pulmonary Artery Involvement in Patients with Takayasu Arteritis.
GCST011936	Ortiz-Fernandez L	2020	76	0	Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.
GCST011934	Ortiz-Fernandez L	2020	57	0	Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.
GCST011935	Ortiz-Fernandez L	2020	46	0	Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	6
Tier 2: splice/UTR	0
Tier 3: regulatory	2
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	42
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	6

Functional consequences

Consequence	Count
intron_variant	25
unknown	7
missense_variant	6
synonymous_variant	4
non_coding_transcript_exon_variant	3
intergenic_variant	3
regulatory_region_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2844678	6	30982273	G>A	0.05	regulatory_region_variant	NAPGP2 - MUC21	6e-47	Tier 3: regulatory
rs12524487	6	31386461	C>T	0.05	intron_variant	MICA-AS1	6e-38	Tier 4: intronic/intergenic
HLA-B*5201							4e-36	Tier 4: intronic/intergenic
rs117298325	6	31312441	T>C	0.05	intron_variant	LINC02571 - HLA-B	4e-34	Tier 4: intronic/intergenic
rs9262437	6	31001408	A>C,G	0.05	non_coding_transcript_exon_variant	MUC21 - MUC22	5e-31	Tier 4: intronic/intergenic
rs17193507	6	31383277	G>T	0.05	intron_variant	MICA-AS1	7e-30	Tier 4: intronic/intergenic
HLA-B*1302							3e-25	Tier 4: intronic/intergenic
HLAB*5201							3e-20	Tier 4: intronic/intergenic
rs61444472	6	31134528	A>G	0.05	intron_variant	PSORS1C1	2e-17	Tier 4: intronic/intergenic
rs45479291	6	29792252	G>C,T	0.05	non_coding_transcript_exon_variant	HLA-V, HLA-V, HLA-F-AS1, HCG4	2e-16	Tier 4: intronic/intergenic
HLAB*1302							2e-16	Tier 4: intronic/intergenic
HLA-B*1501							1e-15	Tier 4: intronic/intergenic
rs2322599	8	27354393	G>A,C	0.21	intron_variant	PTK2B	3e-13	Tier 4: intronic/intergenic
rs2836883	21	39094818	G>A	0.05	intergenic_variant	LINC02940 - RPL23AP12	1e-12	Tier 4: intronic/intergenic
rs10919543	1	161538827	A>G	0.413	intron_variant	RPS23P10 - FCGR3A	6e-12	Tier 4: intronic/intergenic
rs2099684	1	161530340	A>C,G,T	0.26	intron_variant	HSPA6 - RPS23P10	7e-12	Tier 4: intronic/intergenic
rs1265067	6	31148365	G>A,T	0.05	intron_variant	CCHCR1	8e-12	Tier 4: intronic/intergenic
rs62392216	6	29958100	G>A	0.05	non_coding_transcript_exon_variant	HLA-W, POLR1HASP, POLR1HASP	1e-11	Tier 4: intronic/intergenic
HLAB*1501							1e-11	Tier 4: intronic/intergenic
rs9271066	6	32607854	A>C,G	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-11	Tier 4: intronic/intergenic
rs3130618	6	31664357	C>A,G,T	0.05	missense_variant	GPANK1	2e-11	Tier 1: coding
rs3130627	6	31633074	G>T	0.05	intron_variant	PRRC2A	3e-11	Tier 4: intronic/intergenic
rs10573	6	31687661	G>A	0.05	synonymous_variant	ABHD16A	3e-11	Tier 4: intronic/intergenic
rs1576	6	31142614	G>A,C	0.05	missense_variant	CCHCR1	3e-11	Tier 1: coding
rs2517985	6	31151165	T>A,C,G	0.05	intron_variant	CCHCR1	3e-11	Tier 4: intronic/intergenic
rs9267535	6	31681372	C>G,T	0.05	intron_variant	LY6G5C	3e-11	Tier 4: intronic/intergenic
rs3134940	6	32182039	T>C	0.05	intron_variant	AGER	3e-11	Tier 4: intronic/intergenic
rs9267532	6	31672202	C>T	0.05	missense_variant	LY6G5B	3e-11	Tier 1: coding
rs1265078	6	31144825	G>A,C	0.05	intron_variant	CCHCR1	3e-11	Tier 4: intronic/intergenic
rs3130070	6	31624031	A>C,G	0.05	intron_variant	PRRC2A	4e-11	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 62 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

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

Gene	HGNC	Evidence routes
HLA-B	HLA-B	GWAS, Orphanet
HLA-DRB1	HLA-DRB1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROBO1	Orphanet:95496	Pituitary stalk interruption syndrome
BTNL2	Orphanet:797	Sarcoidosis
AICDA	Orphanet:101089	Hyper-IgM syndrome type 2
CAV3	Orphanet:101016	Romano-Ward syndrome
CAV3	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
CAV3	Orphanet:488650	Distal myopathy, Tateyama type
CAV3	Orphanet:97238	Rippling muscle disease
APCDD1	Orphanet:55654	Hypotrichosis simplex
CARD9	Orphanet:457088	Predisposition to invasive fungal disease due to CARD9 deficiency
ZMIZ1	Orphanet:528084	Non-specific syndromic intellectual disability
ZFPM2	Orphanet:2140	Congenital diaphragmatic hernia
ZFPM2	Orphanet:251510	46,XY partial gonadal dysgenesis
ZFPM2	Orphanet:3303	Tetralogy of Fallot
CDC73	Orphanet:143	Parathyroid carcinoma
CDC73	Orphanet:99879	Familial isolated hyperparathyroidism
CDC73	Orphanet:99880	Hyperparathyroidism-jaw tumor syndrome
CDSN	Orphanet:263553	Peeling skin syndrome type B
CDSN	Orphanet:90368	Hypotrichosis simplex of the scalp
CFL2	Orphanet:171436	Typical nemaline myopathy
FRMD4A	Orphanet:466688	Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome
TRANK1	Orphanet:33543	Kleine-Levin syndrome
GRXCR1	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
EPHB4	Orphanet:1053	Vein of Galen malformation
EPHB4	Orphanet:568065	EPHB4-related lymphatic-related hydrops fetalis
EPHB4	Orphanet:693912	EPHB4-related capillary malformation-arteriovenous malformation
EPHB4	Orphanet:90186	Meige disease
FCGR3A	Orphanet:437552	Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity
FOXG1	Orphanet:261144	FOXG1 syndrome due to 14q12 microdeletion
FOXG1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
FOXG1	Orphanet:598164	FOXG1 syndrome due to intragenic alteration
GATA3	Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3	Orphanet:585936	B-lymphoblastic leukemia/lymphoma with hyperdiploidy
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis
HLA-C	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
HLA-DPA1	Orphanet:900	Granulomatosis with polyangiitis
HLA-DQA1	Orphanet:391490	Adult-onset myasthenia gravis
HLA-DQA1	Orphanet:930	Idiopathic achalasia
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid
HLA-DQB1	Orphanet:83465	Narcolepsy type 2
HLA-DQB1	Orphanet:930	Idiopathic achalasia
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome
HLA-DRB1	Orphanet:2073	Narcolepsy type 1
HLA-DRB1	Orphanet:220393	Diffuse cutaneous systemic sclerosis

Cohort genes → proteins

75 cohort genes, 69 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROBO1	HGNC:10249	ENSG00000169855	Q9Y6N7	Roundabout homolog 1	gwas
RPS9	HGNC:10442	ENSG00000170889	P46781	Small ribosomal subunit protein uS4	gwas
SLC14A2	HGNC:10919	ENSG00000132874	Q15849	Urea transporter 2	gwas
SLC16A7	HGNC:10928	ENSG00000118596	O60669	Monocarboxylate transporter 2	gwas
SNAPC4	HGNC:11137	ENSG00000165684	Q5SXM2	snRNA-activating protein complex subunit 4	gwas
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
AICDA	HGNC:13203	ENSG00000111732	Q9GZX7	Single-stranded DNA cytosine deaminase	gwas
ATP8A1	HGNC:13531	ENSG00000124406	Q9Y2Q0	Phospholipid-transporting ATPase IA	gwas
PRRC2A	HGNC:13918	ENSG00000204469	P48634	Protein PRRC2A	gwas
TSBP1	HGNC:13922	ENSG00000204296	Q5SRN2	Testis-expressed basic protein 1	gwas
POLR1HASP	HGNC:13924	ENSG00000204623		POLR1H antisense, pseudogene	gwas
SAPCD1	HGNC:13938	ENSG00000228727	Q5SSQ6	Suppressor APC domain-containing protein 1	gwas
OR14J1	HGNC:13971	ENSG00000204695	Q9UGF5	Olfactory receptor 14J1	gwas
EHMT2	HGNC:14129	ENSG00000204371	Q96KQ7	Histone-lysine N-methyltransferase EHMT2	gwas
CLEC4E	HGNC:14555	ENSG00000166523	Q9ULY5	C-type lectin domain family 4 member E	gwas
CAV3	HGNC:1529	ENSG00000182533	P56539	Caveolin-3	gwas
CACNA2D3	HGNC:15460	ENSG00000157445	Q8IZS8	Voltage-dependent calcium channel subunit alpha-2/delta-3	gwas
APCDD1	HGNC:15718	ENSG00000154856	Q8J025	Protein APCDD1	gwas
SVEP1	HGNC:15985	ENSG00000165124	Q4LDE5	Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1	gwas
DUSP22	HGNC:16077	ENSG00000112679	Q9NRW4	Dual specificity protein phosphatase 22	gwas
CCR7	HGNC:1608	ENSG00000126353	P32248	C-C chemokine receptor type 7	gwas
TRIM31	HGNC:16289	ENSG00000204616	Q9BZY9	E3 ubiquitin-protein ligase TRIM31	gwas
CARD9	HGNC:16391	ENSG00000187796	Q9H257	Caspase recruitment domain-containing protein 9	gwas
ZMIZ1	HGNC:16493	ENSG00000108175	Q9ULJ6	Zinc finger MIZ domain-containing protein 1	gwas
ZFPM2	HGNC:16700	ENSG00000169946	Q8WW38	Zinc finger protein ZFPM2	gwas
CDC73	HGNC:16783	ENSG00000134371	Q6P1J9	Parafibromin	gwas
PSORS1C1	HGNC:17202	ENSG00000204540	Q9UIG5	Psoriasis susceptibility 1 candidate gene 1 protein	gwas
CLNK	HGNC:17438	ENSG00000109684	Q7Z7G1	Cytokine-dependent hematopoietic cell linker	gwas
CDSN	HGNC:1802	ENSG00000204539	Q15517	Corneodesmosin	gwas
RBFOX1	HGNC:18222	ENSG00000078328	Q9NWB1	RNA binding protein fox-1 homolog 1	gwas
SFTA1P	HGNC:18383	ENSG00000225383		surfactant associated 1, lncRNA	gwas
CFL2	HGNC:1875	ENSG00000165410	Q9Y281	Cofilin-2	gwas
KCNT2	HGNC:18866	ENSG00000162687	Q6UVM3	Potassium channel subfamily T member 2	gwas
DCLK3	HGNC:19005	ENSG00000163673	Q9C098	Serine/threonine-protein kinase DCLK3	gwas
NCR3	HGNC:19077	ENSG00000204475	O14931	Natural cytotoxicity triggering receptor 3	gwas
UHMK1	HGNC:19683	ENSG00000152332	Q8TAS1	Serine/threonine-protein kinase Kist	gwas
HCG4	HGNC:21241	ENSG00000176998		HLA complex group 4	gwas
TAFA5	HGNC:21592	ENSG00000219438	Q7Z5A7	Chemokine-like protein TAFA-5	gwas
MUC21	HGNC:21661	ENSG00000204544	Q5SSG8	Mucin-21	gwas
HLA-V	HGNC:23482	ENSG00000181126		major histocompatibility complex, class I, V (pseudogene)	gwas
ATF6B	HGNC:2349	ENSG00000213676	Q99941	Cyclic AMP-dependent transcription factor ATF-6 beta	gwas
ZNF521	HGNC:24605	ENSG00000198795	Q96K83	Zinc finger protein 521	gwas
FRMD4A	HGNC:25491	ENSG00000151474	Q9P2Q2	FERM domain-containing protein 4A	gwas
DDR1	HGNC:2730	ENSG00000204580	Q08345	Epithelial discoidin domain-containing receptor 1	gwas
HCG27	HGNC:27366	ENSG00000206344		HLA complex group 27	gwas
TRANK1	HGNC:29011	ENSG00000168016	O15050	TPR and ankyrin repeat-containing protein 1	gwas
VPS8	HGNC:29122	ENSG00000156931	Q8N3P4	Vacuolar protein sorting-associated protein 8 homolog	gwas
SH2D1B	HGNC:30416	ENSG00000198574	O14796	SH2 domain-containing protein 1B	gwas
PSMG1	HGNC:3043	ENSG00000183527	O95456	Proteasome assembly chaperone 1	gwas
GRXCR1	HGNC:31673	ENSG00000215203	A8MXD5	Glutaredoxin domain-containing cysteine-rich protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROBO1	Roundabout homolog 1	Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuro…
RPS9	Small ribosomal subunit protein uS4	Component of the small ribosomal subunit.
SLC14A2	Urea transporter 2	Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism.
SLC16A7	Monocarboxylate transporter 2	Proton-coupled monocarboxylate symporter.
SNAPC4	snRNA-activating protein complex subunit 4	Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes.
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
AICDA	Single-stranded DNA cytosine deaminase	Single-stranded DNA-specific cytidine deaminase.
ATP8A1	Phospholipid-transporting ATPase IA	Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric dis…
PRRC2A	Protein PRRC2A	May play a role in the regulation of pre-mRNA splicing.
OR14J1	Olfactory receptor 14J1	Odorant receptor.
EHMT2	Histone-lysine N-methyltransferase EHMT2	Histone methyltransferase that specifically mono- and dimethylates ‘Lys-9’ of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin.
CLEC4E	C-type lectin domain family 4 member E	Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of abnormal self and pathogen-associated molecular patterns (PAMPs) of bacteria…
CAV3	Caveolin-3	May act as a scaffolding protein within caveolar membranes.
CACNA2D3	Voltage-dependent calcium channel subunit alpha-2/delta-3	The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
APCDD1	Protein APCDD1	Negative regulator of the Wnt signaling pathway.
SVEP1	Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1	Required for morphological development, cell alignment and migration of lymphatic endothelial cells during embryonic development, potentially via modulation of ANGPT2-TIE1 signaling and subsequent activation of FOXC2 transcription.
DUSP22	Dual specificity protein phosphatase 22	Dual specificity phosphatase; can dephosphorylate both phosphotyrosine and phosphoserine or phosphothreonine residues.
CCR7	C-C chemokine receptor type 7	Receptor for the MIP-3-beta chemokine.
TRIM31	E3 ubiquitin-protein ligase TRIM31	E3 ubiquitin-protein ligase that acts as a regulator of antiviral immune response and inflammation by mediating ubiquitination of substrates.
CARD9	Caspase recruitment domain-containing protein 9	Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors.
ZMIZ1	Zinc finger MIZ domain-containing protein 1	Acts as a transcriptional coactivator.
ZFPM2	Zinc finger protein ZFPM2	Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis.
CDC73	Parafibromin	Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways.
CLNK	Cytokine-dependent hematopoietic cell linker	An adapter protein which plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation.
CDSN	Corneodesmosin	Important for the epidermal barrier integrity.
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
CFL2	Cofilin-2	Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner.
KCNT2	Potassium channel subfamily T member 2	Sodium-activated and chloride-activated potassium channel.
NCR3	Natural cytotoxicity triggering receptor 3	Cell membrane receptor of natural killer/NK cells that is activated by binding of extracellular ligands including BAG6 and NCR3LG1.
UHMK1	Serine/threonine-protein kinase Kist	Upon serum stimulation, phosphorylates CDKN1B/p27Kip1, thus controlling CDKN1B subcellular location and cell cycle progression in G1 phase.
TAFA5	Chemokine-like protein TAFA-5	Acts as a chemokine-like protein by regulating cell proliferation and migration through activation of G protein-coupled receptors (GPCRs), such as S1PR2 and FPR2.
ATF6B	Cyclic AMP-dependent transcription factor ATF-6 beta	Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 beta), which is embedded in the endoplasmic reticulum membrane.
ZNF521	Zinc finger protein 521	Transcription factor that can both act as an activator or a repressor depending on the context.
FRMD4A	FERM domain-containing protein 4A	Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex.
DDR1	Epithelial discoidin domain-containing receptor 1	Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell prolifer…
VPS8	Vacuolar protein sorting-associated protein 8 homolog	Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway.
SH2D1B	SH2 domain-containing protein 1B	Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244.
PSMG1	Proteasome assembly chaperone 1	Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2.
GRXCR1	Glutaredoxin domain-containing cysteine-rich protein 1	May play a role in actin filament architecture in developing stereocilia of sensory cells.
EPHB4	Ephrin type-B receptor 4	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
AIF1	Allograft inflammatory factor 1	Actin-binding protein that enhances membrane ruffling and RAC activation.
FCGR2A	Low affinity immunoglobulin gamma Fc region receptor II-a	Binds to the Fc region of immunoglobulins gamma.
FCGR3A	Low affinity immunoglobulin gamma Fc region receptor III-A	Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG).
FOXG1	Forkhead box protein G1	Transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon.
GATA3	Trans-acting T-cell-specific transcription factor GATA-3	Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.
GPR65	G-protein coupled receptor 65	Proton-sensing G-protein coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions.
GPX5	Epididymal secretory glutathione peroxidase	Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.
H2BC9	Histone H2B type 1-H	Core component of nucleosome.
H3C8	Histone H3.1	Core component of nucleosome.
HIVEP1	Zinc finger protein 40	This protein specifically binds to the DNA sequence 5’-GGGACTTTCC-3’ which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1.

Protein-family classification

Druggable: 29 · Difficult: 15 · Unknown: 31 · Druggable fraction: 0.39

Family distribution

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

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	14	5.5×	2e-06
Complement	1	3.6×	0.652
Transporter	2	2.1×	0.652
Kinase	4	1.5×	0.652
Transcription factor	11	1.2×	0.652
Ion channel	1	1.5×	0.779
Phosphatase	1	1.1×	0.779
GPCR	3	1.0×	0.779
Scaffold/PPI	4	0.9×	0.779
Other/Unknown	31	0.7×	0.996
Enzyme (other)	3	0.5×	0.996

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROBO1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
RPS9	Other/Unknown	no		Ribosomal_uS4_N, S4_RNA-bd, Ribosomal_uS4_euk_arc
SLC14A2	Transporter	yes		Urea_transporter, Ammonium/urea_transptr
SLC16A7	Transporter	yes		MCT, MFS, MFS_dom
SNAPC4	Transcription factor	no		SANT/Myb, Homeodomain-like_sf, SANT_dom
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
AICDA	Enzyme (other)	yes	3.5.4.38	CMP_dCMP_dom, AID, APOBEC/CMP_deaminase_Zn-bd
ATP8A1	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
PRRC2A	Other/Unknown	no		BAT2_N, PRRC2
TSBP1	Other/Unknown	no		TSBP1
POLR1HASP	Other/Unknown	no
SAPCD1	Other/Unknown	no		SAPC2_1/2
OR14J1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
EHMT2	Scaffold/PPI	no	2.1.1.355	SET_dom, Ankyrin_rpt, Pre-SET_dom
CLEC4E	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
CAV3	Other/Unknown	no		Caveolin, Caveolin_CS
CACNA2D3	Other/Unknown	no		VWF_A, VWA_N, VDCC_a2/dsu
APCDD1	Other/Unknown	no		APCDD1_dom, APCDD1
SVEP1	Complement	yes		EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, EGF
DUSP22	Phosphatase	yes		Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, TYR_PHOSPHATASE_DUAL_dom
CCR7	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR7
TRIM31	Transcription factor	no		Znf_B-box, Znf_RING, Znf_RING/FYVE/PHD
CARD9	Other/Unknown	no		CARD, DEATH-like_dom_sf, CARD_CARD9
ZMIZ1	Transcription factor	no		Znf_MIZ, Znf_RING/FYVE/PHD, ZMIZ1_N
ZFPM2	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_FOG, Znf_C2H2_sf
CDC73	Other/Unknown	no		Cdc73/Parafibromin, CDC73_C, Cdc73_N
PSORS1C1	Other/Unknown	no		SEEK1
CLNK	Scaffold/PPI	no		SH2, SH2_dom_sf, Immunoreceptor_sig_adapters
CDSN	Other/Unknown	no		Corneodesmosin
RBFOX1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
SFTA1P	Other/Unknown	no
CFL2	Other/Unknown	no		ADF-H, ADF/Cofilin, ADF-H/Gelsolin-like_dom_sf
KCNT2	Ion channel	yes		RCK_N, K_chnl_BK_asu, K_chnl_dom
DCLK3	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
NCR3	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
UHMK1	Kinase	yes		RRM_dom, Prot_kinase_dom, Kinase-like_dom_sf
HCG4	Other/Unknown	no
TAFA5	Other/Unknown	no		Chemokine-like_TAFA, TAFA-5
MUC21	Other/Unknown	no		Tandem-repeating_mucin, Mucin_dom
HLA-V	Other/Unknown	no
ATF6B	Transcription factor	no		bZIP, bZIP_sf, ATF_bZIP_TF
ZNF521	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
FRMD4A	Other/Unknown	no		FERM_domain, PH-like_dom_sf, FERM/acyl-CoA-bd_prot_sf
DDR1	Kinase	yes	2.7.10.1	FA58C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
HCG27	Other/Unknown	no
TRANK1	Scaffold/PPI	no		Ankyrin_rpt, TPR-like_helical_dom_sf, TPR_rpt
VPS8	Transcription factor	no		WD40_rpt, Znf_RING, Quino_amine_DH_bsu
SH2D1B	Scaffold/PPI	no		SH2, EAT2_SH2, SH2_dom_sf
PSMG1	Other/Unknown	no		Proteasome_assmbl_chp_1
GRXCR1	Other/Unknown	no		Glutaredoxin, Thioredoxin-like_sf, GRXCR1

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	4
broad (>20)	70
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	12
leukocyte	10
male germ line stem cell (sensu Vertebrata) in testis	8
blood	8
granulocyte	8
primordial germ cell in gonad	6
sural nerve	6
left testis	6
right testis	6
endothelial cell	5
testis	5
spleen	5
ganglionic eminence	4
ventricular zone	4
right uterine tube	4
lymph node	4
Brodmann (1909) area 23	4
colonic epithelium	4
vermiform appendix	4
calcaneal tendon	4

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROBO1	287	ubiquitous	marker	ventricular zone, ganglionic eminence, tibia
RPS9	146	ubiquitous	marker	monocyte, leukocyte, left ovary
SLC14A2	100	tissue_specific	marker	primordial germ cell in gonad, hair follicle, right adrenal gland
SLC16A7	286	ubiquitous	marker	heart right ventricle, renal medulla, vena cava
SNAPC4	249	ubiquitous	yes	sural nerve, endothelial cell, right uterine tube
BTNL2	106		yes	sural nerve, ventricular zone, primordial germ cell in gonad
AICDA	121	tissue_specific	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, lymph node
ATP8A1	292	ubiquitous	marker	Brodmann (1909) area 23, corpus callosum, endothelial cell
PRRC2A	134	ubiquitous	marker	right testis, left testis, ventricular zone
TSBP1	58	tissue_specific	yes	left testis, testis, right testis
POLR1HASP	134	ubiquitous	marker	right testis, left testis, testis
SAPCD1	133	tissue_specific	yes	skin of leg, right uterine tube, zone of skin
OR14J1	3		marker	bone marrow cell, colonic epithelium, hindlimb stylopod muscle
EHMT2	134	ubiquitous	marker	nucleus accumbens, ganglionic eminence, putamen
CLEC4E	173	broad	marker	monocyte, mononuclear cell, leukocyte
CAV3	157	tissue_specific	yes	hindlimb stylopod muscle, vastus lateralis, triceps brachii
CACNA2D3	205	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell
APCDD1	249	broad	marker	upper arm skin, nipple, decidua
SVEP1	225	broad	marker	pericardium, lower lobe of lung, placenta
DUSP22	286	ubiquitous	marker	secondary oocyte, cervix squamous epithelium, gingival epithelium
CCR7	169	broad	marker	vermiform appendix, lymph node, blood
TRIM31	124	tissue_specific	marker	mucosa of transverse colon, rectum, duodenum
CARD9	172	broad	marker	monocyte, mononuclear cell, leukocyte
ZMIZ1	295	ubiquitous	marker	dorsal motor nucleus of vagus nerve, tibia, seminal vesicle
ZFPM2	239	ubiquitous	marker	skeletal muscle tissue of biceps brachii, germinal epithelium of ovary, biceps brachii
CDC73	271	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium
PSORS1C1	124	ubiquitous	yes	left testis, right testis, testis
CLNK	106	tissue_specific	marker	skeletal muscle tissue of rectus abdominis, buccal mucosa cell, adult mammalian kidney
CDSN	101	tissue_specific	yes	skin of abdomen, zone of skin, skin of leg
RBFOX1	220	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cortical plate

Protein interactions among cohort

Intra-cohort edges: 37.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPS9	6,407
GATA3	5,990
EHMT2	4,723
CDC73	4,592
AIF1	4,440
CFL2	4,226
CARD9	3,636
H3C8	3,550
FCGR3A	3,492
H2BC9	3,448

Intra-cohort edges

A	B	Sources
APCDD1	CDSN	string_interaction
ATP8A1	GRXCR1	string_interaction
BTNL2	HLA-DQB1	intact
BTNL2	HLA-DRA	string_interaction
BTNL2	HLA-DRB1	string_interaction
BTNL2	TSBP1	string_interaction
CARD9	CLEC4E	string_interaction
CARD9	SNAPC4	string_interaction
CCR7	ZMIZ1	biogrid_interaction
CDC73	SLC14A2	biogrid_interaction
CDSN	PSORS1C1	string_interaction
CLEC4E	HLA-C	biogrid_interaction
DUSP22	KLHL33	string_interaction
EHMT2	GATA3	intact
EPHB4	HLA-DRA	biogrid_interaction, intact
FCGR2A	FCGR3A	string_interaction
FCGR3A	NCR3	string_interaction
GATA3	ZFPM2	intact
H2BC9	HIVEP1	intact
H2BC9	PRRC2A	intact
HLA-B	HLA-C	biogrid_interaction, intact
HLA-B	HLA-DOB	string_interaction
HLA-B	HLA-G	biogrid_interaction, intact
HLA-B	PRRC2A	string_interaction
HLA-B	PSORS1C1	string_interaction
HLA-C	HLA-DQB1	intact
HLA-C	HLA-G	biogrid_interaction
HLA-C	NCR3	biogrid_interaction
HLA-DOB	HLA-DRA	string_interaction
HLA-DPA1	HLA-DQB1	intact
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
HLA-DRA	HLA-DRB1	biogrid_interaction, intact, string_interaction
HLA-DRA	TSBP1	string_interaction
HLA-DRB1	TSBP1	string_interaction
OR14J1	TSBP1	string_interaction
PSORS1C1	TSBP1	string_interaction
ROBO1	SH2D1B	biogrid_interaction

Structural data

PDB: 41 · AlphaFold-only: 28 · No structure: 6

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
H3C8	P68431	548
HLA-B	P01889	237
RPS9	P46781	213
HLA-DRA	P01903	140
HLA-DRB1	P01911	108
EHMT2	Q96KQ7	35
DDR1	Q08345	34
HLA-DQA1	P01909	28
EPHB4	P54760	23
CDC73	Q6P1J9	20
SNAPC4	Q5SXM2	18
FCGR3A	P08637	15
PSMG1	O95456	13
HLA-C	P10321	13
ROBO1	Q9Y6N7	12
CFL2	Q9Y281	11
HLA-DPA1	P20036	10
HLA-DQB1	P01920	10
HLA-G	P17693	10
SLC14A2	Q15849	9
FCGR2A	P12318	9
ATP8A1	Q9Y2Q0	8
DUSP22	Q9NRW4	8
CARD9	Q9H257	8
CCR7	P32248	7
AICDA	Q9GZX7	5
RBFOX1	Q9NWB1	4
NCR3	O14931	4
SLC16A7	O60669	3
GATA3	P23771	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KLHL33	A6NCF5	90.82
UHMK1	Q8TAS1	90.31
CAV3	P56539	88.54
OR14J1	Q9UGF5	87.60
BTNL2	Q9UIR0	85.97
TAFA5	Q7Z5A7	83.74
CACNA2D3	Q8IZS8	83.30
APCDD1	Q8J025	82.10
TMEM114	B3SHH9	81.80
KCNT2	Q6UVM3	76.42
SAPCD1	Q5SSQ6	75.98
GRXCR1	A8MXD5	75.36
VPS8	Q8N3P4	74.77
MUC21	Q5SSG8	74.30
MUC22	E2RYF6	67.14
DCLK3	Q9C098	63.27
FRMD4A	Q9P2Q2	62.95
ZNF521	Q96K83	61.75
CLNK	Q7Z7G1	56.93
ATF6B	Q99941	55.31
PSORS1C1	Q9UIG5	55.10
ZFPM2	Q8WW38	51.93
TSBP1	Q5SRN2	45.58
PRRC2A	P48634	40.07
CDSN	Q15517	38.13
SVEP1	Q4LDE5
TRANK1	O15050
GPX6	P59796

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 311. Enrichment computed across 97 evidence-associated genes (66 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 66 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	9	17.1×	7e-07	TRIM31, HLA-B, HLA-C, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1 (+1 more)
Generation of second messenger molecules	5	26.2×	1e-04	HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB1, PLCG2
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	8	10.6×	1e-04	NCR3, SH2D1B, FCGR3A, HLA-B, HLA-C, HLA-G, LILRA3, LILRB3
Translocation of ZAP-70 to Immunological synapse	4	38.5×	2e-04	HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB1
Phosphorylation of CD3 and TCR zeta chains	4	33.0×	4e-04	HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB1
Co-inhibition by PD-1	4	31.5×	4e-04	HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB1
Endosomal/Vacuolar pathway	3	47.2×	0.001	HLA-B, HLA-C, HLA-G
Role of phospholipids in phagocytosis	3	20.8×	0.015	FCGR2A, FCGR3A, PLCG2
Dectin-2 family	3	19.2×	0.017	CLEC4E, MUC21, PLCG2
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	3	17.9×	0.019	HLA-B, HLA-C, HLA-G
MHC class II antigen presentation	5	6.8×	0.024	HLA-DOB, HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB1
FCGR3A-mediated IL10 synthesis	3	13.3×	0.038	FCGR2A, FCGR3A, PLCG2
Downstream TCR signaling	4	7.8×	0.041	HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB1
Pre-NOTCH Transcription and Translation	4	7.4×	0.045	H2BC9, H3C8, RBPJ, NOTCH4
FCGR activation	2	26.6×	0.051	FCGR2A, FCGR3A
FOXO-mediated transcription of cell cycle genes	2	20.4×	0.080	FOXG1, KLF4
Senescence-Associated Secretory Phenotype (SASP)	4	6.0×	0.080	EHMT2, H2BC9, H3C8, IL6
NOTCH4 Intracellular Domain Regulates Transcription	2	17.3×	0.101	RBPJ, NOTCH4
Chromatin modifications during the maternal to zygotic transition (MZT)	3	7.4×	0.119	AICDA, H2BC9, H3C8
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex	3	7.4×	0.119	EHMT2, H2BC9, H3C8
DAP12 interactions	2	14.4×	0.124	HLA-B, HLA-C
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	3	6.9×	0.125	EHMT2, H2BC9, H3C8
Interferon alpha/beta signaling	3	6.9×	0.125	HLA-B, HLA-C, HLA-G
Defective Mismatch Repair Associated With MSH6	1	86.5×	0.138	MSH6
Notch-HLH transcription pathway	2	12.4×	0.138	RBPJ, NOTCH4
Olfactory Signaling Pathway	3	6.6×	0.138	OR14J1, OR2J2, OR2J3
ER-Phagosome pathway	3	5.9×	0.158	HLA-B, HLA-C, HLA-G
Meiotic recombination	3	5.9×	0.158	H2BC9, H3C8, MSH5
TWIK related potassium channel (TREK)	1	57.7×	0.176	KCNK10
Defective Mismatch Repair Associated With MSH2	1	57.7×	0.176	MSH6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 83 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	6	76.1×	8e-08	HLA-DOB, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
adaptive immune response	11	11.2×	2e-06	SH2D1B, HLA-B, HLA-C, HLA-DOB, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRA (+3 more)
antigen processing and presentation of exogenous peptide antigen via MHC class II	6	39.3×	2e-06	HLA-DOB, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
positive regulation of T cell mediated cytotoxicity	6	36.9×	2e-06	HLA-B, HLA-C, HLA-DRA, HLA-DRB1, HLA-G, IL12B
positive regulation of immune response	6	34.8×	3e-06	HLA-DOB, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
immune response	13	7.4×	3e-06	CCR7, NCR3, FCGR3A, GPR65, HLA-B, HLA-C, HLA-DPA1, HLA-DQA1 (+5 more)
positive regulation of T cell activation	6	32.1×	3e-06	HLA-DOB, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
regulation of T-helper cell differentiation	3	152.3×	5e-05	GATA3, HLA-DRA, HLA-DRB1
positive regulation of memory T cell differentiation	3	67.7×	9e-04	HLA-DRA, HLA-DRB1, IL12B
humoral immune response	5	16.9×	1e-03	GATA3, HLA-DQB1, HLA-DRB1, RBPJ, IL6
positive regulation of T cell proliferation	5	15.6×	0.001	BTNL2, AIF1, HLA-DPA1, IL12B, IL6
positive regulation of tumor necrosis factor production	6	11.1×	0.001	CARD9, FCGR2A, FCGR3A, IL12B, IL6, PLCG2
antigen processing and presentation of endogenous peptide antigen via MHC class II	2	203.0×	0.002	HLA-DRA, HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	3	46.9×	0.002	HLA-B, HLA-C, HLA-G
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	3	46.9×	0.002	HLA-B, HLA-C, HLA-G
positive regulation of interleukin-12 production	4	18.9×	0.003	CCR7, HLA-G, IL12B, PLCG2
myeloid dendritic cell antigen processing and presentation	2	135.4×	0.003	HLA-DRA, HLA-DRB1
pyramidal neuron migration to cerebral cortex	2	135.4×	0.003	ZMIZ1, FOXG1
antifungal innate immune response	3	33.8×	0.004	CLEC4E, CARD9, PLCG2
positive regulation of CD4-positive, alpha-beta T cell activation	2	101.5×	0.006	HLA-DRA, HLA-DRB1
positive regulation of macrophage cytokine production	3	26.5×	0.008	CARD9, HLA-G, PLCG2
axon midline choice point recognition	2	81.2×	0.008	ROBO1, FOXG1
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	2	81.2×	0.008	HLA-DRA, HLA-DRB1
negative regulation of mammary gland epithelial cell proliferation	2	81.2×	0.008	ROBO1, GATA3
T cell receptor signaling pathway	5	9.2×	0.008	BTNL2, GATA3, HLA-DQB1, HLA-DRB1, PLCG2
negative regulation of smooth muscle cell proliferation	3	22.6×	0.010	AIF1, IL12B, KLF4
antibody-dependent cellular cytotoxicity	2	67.7×	0.010	FCGR2A, FCGR3A
protection from natural killer cell mediated cytotoxicity	2	67.7×	0.010	HLA-B, HLA-G
positive regulation of interleukin-17 production	3	21.8×	0.010	CARD9, IL12B, IL6
natural killer cell activation	3	21.0×	0.011	NCR3, FCGR3A, IL12B

Therapeutics

Drugs indicated for this disease

0 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Azathioprine	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Tocilizumab	Phase 3 (in late-stage trials)
Tofacitinib	Phase 3 (in late-stage trials)
Upadacitinib	Phase 3 (in late-stage trials)
Ustekinumab	Phase 3 (in late-stage trials)

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

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 8 · Phased (≥1): 11 · Undrugged: 64

Druggability breadth: 35 of 97 evidence-associated genes (36%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

Symbol	Example approved molecule
RPS9	GENTAMICIN SULFATE
EHMT2	RALTITREXED
CACNA2D3	NIMODIPINE
DCLK3	FEDRATINIB
DDR1	PONATINIB
EPHB4	PONATINIB
GPR65	NEFAZODONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDR1	77	4
EPHB4	46	4
DCLK3	20	4
GPR65	11	4
EHMT2	7	4
CCR7	3	3
CACNA2D3	2	4
RPS9	1	4
SLC16A7	1	1
SNAPC4	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS9
RALTITREXED	4	EHMT2
TAZEMETOSTAT	4	EHMT2
DISULFIRAM	4	EHMT2
NIMODIPINE	4	CACNA2D3
TACRINE	4	CACNA2D3
FEDRATINIB	4	DCLK3, DDR1, EPHB4
RUXOLITINIB	4	DCLK3
TOFACITINIB CITRATE	4	DCLK3
TOFACITINIB	4	DCLK3
BOSUTINIB	4	DCLK3, DDR1, EPHB4
NINTEDANIB	4	DCLK3, DDR1, EPHB4
SUNITINIB	4	DCLK3, DDR1, EPHB4
GEFITINIB	4	DCLK3, EPHB4
PONATINIB	4	DDR1, EPHB4
TIVOZANIB	4	DDR1, EPHB4
LENVATINIB	4	DDR1
AXITINIB	4	DDR1
SORAFENIB	4	DDR1, EPHB4
DASATINIB ANHYDROUS	4	DDR1, EPHB4
REGORAFENIB	4	DDR1
ENTRECTINIB	4	DDR1
PACRITINIB	4	DDR1
CABOZANTINIB	4	DDR1
VANDETANIB	4	DDR1, EPHB4
NILOTINIB	4	DDR1, EPHB4
TOVORAFENIB	4	DDR1, EPHB4
PAZOPANIB	4	DDR1
DASATINIB	4	DDR1, EPHB4
ERLOTINIB	4	DDR1, EPHB4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
EHMT2	442	Binding:435, Functional:6, ADMET:1
EPHB4	437	Binding:437
DDR1	422	Binding:422
DCLK3	108	Binding:108
RPS9	90	Binding:90
CCR7	46	Binding:33, Functional:13
HIVEP1	26	Binding:26
CLEC4E	19	Binding:19
DUSP22	19	Binding:19
GPR65	17	Functional:14, Binding:3
HLA-DRB1	17	Binding:17
CACNA2D3	13	Binding:13
CDC73	8	Binding:8
KCNT2	7	Binding:7
SNAPC4	6	Binding:6
SLC16A7	5	Binding:3, Functional:2
PSMG1	5	Binding:5
HLA-DQA1	2	Binding:2
AICDA	1	Binding:1
PRRC2A	1	Binding:1
FCGR2A	1	Binding:1
HLA-B	1	Binding:1
HLA-C	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AICDA	3.5.4.38	single-stranded DNA cytosine deaminase
ATP8A1	7.6.2.1	P-type phospholipid transporter
EHMT2	2.1.1.355, 2.1.1.356, 2.1.1.367, 2.1.1.368	[histone H3]-lysine9 N-trimethyltransferase, [histone H3]-lysine27 N-trimethyltransferase, [histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine9 N-dimethyltransferase
DDR1	2.7.10.1	receptor protein-tyrosine kinase
EPHB4	2.7.10.1	receptor protein-tyrosine kinase
GPX5	1.11.1.9	glutathione peroxidase
GPX6	1.11.1.9	glutathione peroxidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EHMT2	442
DCLK3	108
DDR1	422
EPHB4	437

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

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.

Compound	Max phase	Cohort target (bioactivity)
GENTAMICIN SULFATE	4	RPS9
RALTITREXED	4	EHMT2
TAZEMETOSTAT	4	EHMT2
DISULFIRAM	4	EHMT2
NIMODIPINE	4	CACNA2D3
TACRINE	4	CACNA2D3
FEDRATINIB	4	DCLK3, DDR1, EPHB4
RUXOLITINIB	4	DCLK3
TOFACITINIB CITRATE	4	DCLK3
BOSUTINIB	4	DCLK3, DDR1, EPHB4
NINTEDANIB	4	DCLK3, DDR1, EPHB4
SUNITINIB	4	DCLK3, DDR1, EPHB4
GEFITINIB	4	DCLK3, EPHB4
PONATINIB	4	DDR1, EPHB4
TIVOZANIB	4	DDR1, EPHB4
LENVATINIB	4	DDR1
AXITINIB	4	DDR1
SORAFENIB	4	DDR1, EPHB4
DASATINIB ANHYDROUS	4	DDR1, EPHB4
REGORAFENIB	4	DDR1
ENTRECTINIB	4	DDR1
PACRITINIB	4	DDR1
CABOZANTINIB	4	DDR1
VANDETANIB	4	DDR1, EPHB4
NILOTINIB	4	DDR1, EPHB4
TOVORAFENIB	4	DDR1, EPHB4
PAZOPANIB	4	DDR1
DASATINIB	4	DDR1, EPHB4
ERLOTINIB	4	DDR1, EPHB4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	RPS9, EHMT2, CACNA2D3, DCLK3, DDR1, EPHB4, GPR65
B	Phased (≥1) drug, not yet approved	4	SLC16A7, SNAPC4, CCR7, CDC73
C	Druggable family + PDB, no drug	17	ROBO1, SLC14A2, AICDA, DUSP22, NCR3, FCGR2A, FCGR3A, GPX5, HLA-B, HLA-C (+7 more)
D	Druggable family + AlphaFold only, no drug	6	BTNL2, OR14J1, SVEP1, KCNT2, UHMK1, GPX6
E	Difficult family or no structure, no drug	41	ATP8A1, PRRC2A, TSBP1, POLR1HASP, SAPCD1, CLEC4E, CAV3, APCDD1, TRIM31, CARD9 (+31 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ROBO1	0	—
SLC14A2	0	—
BTNL2	0	—
AICDA	1	—
ATP8A1	0	—
PRRC2A	1	—
TSBP1	0	—
POLR1HASP	0	—
SAPCD1	0	—
OR14J1	0	—
CLEC4E	19	—
CAV3	0	—
APCDD1	0	—
SVEP1	0	—
DUSP22	19	—
TRIM31	0	—
CARD9	0	—
ZMIZ1	0	—
ZFPM2	0	—
PSORS1C1	0	—
CLNK	0	—
CDSN	0	—
RBFOX1	0	—
SFTA1P	0	—
CFL2	0	—
KCNT2	7	—
NCR3	0	—
UHMK1	0	—
HCG4	0	—
TAFA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 74.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	48
PHASE4	10
PHASE2	9
PHASE3	5
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04300686	PHASE4	RECRUITING	A Pilot Study in Severe Patients With Takayasu Arteritis.
NCT05102448	PHASE4	RECRUITING	Comparison of Tofacitinib and Methotrexate in Takayasu’s Arteritis
NCT06498089	PHASE4	RECRUITING	A Randomized, Controlled, Open-label, Multicenter Clinical Trial Comparing the Efficacy and Safety of a Precision Treatment Regimen Based on Clinical-molecular Phenotypes with a Conventional Treatment Regimen in the Treatment of Patients with Active Takayasu’s Arteritis
NCT07013838	PHASE4	NOT_YET_RECRUITING	The Efficacy and Safety of Deucravacitinib in Takayasu’s Arteritis
NCT07087912	PHASE4	RECRUITING	Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
NCT07325357	PHASE4	NOT_YET_RECRUITING	Effect of Pirfenidone on TA Fibrosis
NCT07451665	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Vunakizumab and Ivarmacitinib in the Treatment of Active Takayasu’s Arteritis
NCT04299971	PHASE4	UNKNOWN	Efficiency of Methotrexate and Tofacitinib in Mild and Moderate Patients
NCT05151848	PHASE4	UNKNOWN	Comparison of Adalimumab and Tofacitinib in the Treatment of Active Takayasu Arteritis
NCT06390111	PHASE4	WITHDRAWN	A Trial to Evaluate Efficacy of Reinduction With Nadofaragene Firadenovec in Subjects With CIS ± High-grade Ta/T1 and no Complete Response to First Nadofaragene Firadenovec Dose.
NCT04161898	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Upadacitinib in Participants With Takayasu Arteritis (TAK)
NCT02101333	PHASE3	COMPLETED	Efficacy and Tolerance of Tocilizumab In Takayasu Arteritis
NCT03096275	PHASE3	COMPLETED	Comparison of Mycophenolate Mofetil and Cyclophosphamide for Active Takayasu’s Arteritis
NCT03550781	PHASE2/PHASE3	UNKNOWN	Anti-inflammatory Treatment for Inactive Takayasu Arteritis
NCT04882072	PHASE3	TERMINATED	A Study of Ustekinumab in Participants With Takayasu Arteritis (TAK)
NCT05749666	PHASE3	UNKNOWN	Comparison of Tofacitinib and Prednisolone in the Treatment of Active Takayasu’s Arteritis
NCT06887062	PHASE2	RECRUITING	Dapagliflozin and Endothelin Receptor Antagonism in Large Vessel Vasculitis (DERAIL-LVV)
NCT07477795	PHASE2	NOT_YET_RECRUITING	Phase II Interventional Study Evaluating Efficacy and Safety of Secukinumab in Active Severe Takayasu Patients
NCT00556439	PHASE2	COMPLETED	Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu’s Arteritis
NCT01988506	PHASE2	COMPLETED	Induction of Regulatory t Cells by Low Dose il2 in Autoimmune and Inflammatory Diseases
NCT02457585	PHASE2	UNKNOWN	Clinical Study of Anti-tumor Necrosis Factor Therapy in Patients With Takayasu Arteritis
NCT03482479	PHASE2	COMPLETED	Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis
NCT04564001	PHASE2	UNKNOWN	Multicentre, Randomized, Prospective Trial Evaluating the Efficacy and Safety of Infliximab to Tocilizumab in Refractory or Relapsing Takayasu Arteritis
NCT05168475	PHASE2	TERMINATED	Biologics in Refractory Vasculitis: A Trial of Biologic Therapy for Refractory Primary Non-ANCA Associated Vasculitis
NCT06662721	PHASE2	COMPLETED	Baricitinib for Refractory Takayasu Arteritis
NCT02925351	EARLY_PHASE1	COMPLETED	Fluorine F 18 Clofarabine PET/CT in Imaging Patients With Autoimmune or Inflammatory Diseases
NCT01241305	Not specified	RECRUITING	One-Time DNA Study for Vasculitis
NCT02257866	Not specified	RECRUITING	Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis
NCT02593565	Not specified	RECRUITING	Vasculitis Pregnancy Registry
NCT02964364	Not specified	RECRUITING	China Takayasu Arteritis Registry (CTA Registry)
NCT02967068	Not specified	RECRUITING	VCRC Tissue Repository
NCT03372980	Not specified	RECRUITING	A Registry Study on Biomarkers of Takayasu’s Arteritis (ARSBTA)
NCT03893136	Not specified	RECRUITING	The Registry Study of Takayasu Arteritis in East China
NCT04071691	Not specified	ACTIVE_NOT_RECRUITING	PET Imaging of Giant Cell and Takayasu Arteritis
NCT05904301	Not specified	RECRUITING	Armenian NAtionwide REGistry of Systemic Autoimmune and Autoinflammatory Diseases
NCT06178419	Not specified	RECRUITING	Remote Ischemic Conditioning for Cerebral Ischemia in Patients With Takayasu Arteritis (TARIC-1)
NCT06766552	Not specified	NOT_YET_RECRUITING	A Registry Study Assessing PRO, Dosing Patterns, and Safety of Vunakizumab in Patients With General Rheumatic Diseases.
NCT06807788	Not specified	ACTIVE_NOT_RECRUITING	Evaluation of Platelet Aggregability in Patients with Takayasu’s Arteritis
NCT07077304	Not specified	NOT_YET_RECRUITING	EACVI Study on Multimodality Cardiovascular Imaging of Inflammatory Cardiovascular Diseases
NCT07276087	Not specified	RECRUITING	Physical and Psychosocial Parameters in Takayasu Arteritis and Behçet’s Disease: A Comparative Study With Healthy Controls

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TOFACITINIB	4	15
ADALIMUMAB	4	4
CRAVACITINIB	4	3
TOCILIZUMAB	4	3
ABATACEPT	4	1
BOSENTAN	4	1
CERTOLIZUMAB PEGOL	4	1
LEFLUNOMIDE	4	1
PIRFENIDONE	4	1
UPADACITINIB	4	1
USTEKINUMAB	4	1
IVARMACITINIB	3	1
NADOFARAGENE FIRADENOVEC	3	1
YELLOW FEVER VACCINE	3	1
CHEMBL4783966	0	1
CHEMBL4787173	0	1