Antiphospholipid syndrome

Summary

Antiphospholipid syndrome (MONDO:8000010) is a disease with 14 cohort genes (15 GWAS associations across 1 studies) and 98 clinical trials. Top therapeutic interventions include hydroxychloroquine, warfarin, and acetaminophen.

At a glance

• Cohort genes: 14
• GWAS associations: 15
• Phenotypes (HPO): 39
• Clinical trials: 98

Clinical features

Signs & symptoms

Clinical features (HPO)

39 HPO clinical features (Orphanet curated; top 39 by frequency):

HPO ID	Term	Frequency
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0001622	Premature birth	Frequent (30-79%)
HP:0002140	Ischemic stroke	Frequent (30-79%)
HP:0002326	Transient ischemic attack	Frequent (30-79%)
HP:0003613	Antiphospholipid antibody positivity	Frequent (30-79%)
HP:0004420	Arterial thrombosis	Frequent (30-79%)
HP:0004936	Venous thrombosis	Frequent (30-79%)
HP:0008222	Female infertility	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0020136	Anticardiolipin IgG antibody positivity	Frequent (30-79%)
HP:0020137	Anticardiolipin IgM antibody positivity	Frequent (30-79%)
HP:0025343	Lupus anticoagulant	Frequent (30-79%)
HP:0032376	Anti-beta 2 glycoprotein I antibody positivity	Frequent (30-79%)
HP:0033260	Livedo racemosa	Frequent (30-79%)
HP:0033505	Livedo reticularis	Frequent (30-79%)
HP:0034156	Anti-beta-2-Glycoprotein I IgG antibody positivity	Frequent (30-79%)
HP:0034157	Anti-beta-2-Glycoprotein I IgM antibody positivity	Frequent (30-79%)
HP:0100602	Preeclampsia	Frequent (30-79%)
HP:0100724	Hypercoagulability	Frequent (30-79%)
HP:0034098	Anti-phosphatidyl glycerol antibody positivity	Occasional (5-29%)
HP:0034099	Anti-phosphatidyl inositol antibody positivity	Occasional (5-29%)
HP:0034100	Anti-phosphatidyl serine antibody positivity	Occasional (5-29%)
HP:0034101	Anti-annexin-V antibody positivity	Occasional (5-29%)
HP:0100758	Gangrene	Occasional (5-29%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001268	Mental deterioration	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0001650	Aortic valve stenosis	Occasional (5-29%)
HP:0001653	Mitral regurgitation	Occasional (5-29%)
HP:0001659	Aortic regurgitation	Occasional (5-29%)
HP:0001718	Mitral stenosis	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0002092	Pulmonary arterial hypertension	Occasional (5-29%)
HP:0034084	Anti-phosphatidyl ethanolamine antibody positivity	Occasional (5-29%)
HP:0034097	Anti-phosphatidyl choline antibody positivity	Occasional (5-29%)
HP:0025420	Diffuse alveolar hemorrhage	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	antiphospholipid syndrome
Mondo ID	MONDO:8000010
EFO	EFO:0002689
MeSH	D016736
Orphanet	80
DOID	DOID:2988
ICD-10-CM	D68.61
ICD-11	1173370808
NCIT	C61283
SNOMED CT	26843008
UMLS	C0085278
MedGen	38834
GARD	0005824
Is cancer (heuristic)	no

Also known as: antiphospholipid antibody syndrome · antiphospholipid syndrome · familial lupus anticoagulant · Hughes syndrome

Data availability: 15 GWAS associations (1 study) · 18 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, infantile spasms, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, 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

Subtypes (4): primary antiphospholipid syndrome, catastrophic antiphospholipid syndrome, secondary antiphospholipid syndrome, familial antiphospholipid syndrome

Genetics & variants

GWAS landscape

15 GWAS associations across 1 studies. Top hits map to 7 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs79154414	5e-08	LINC01812 - FBXL12P1	T	6.2
rs2288493	8e-08	TSHR-AS1, TSHR	T	6.18
rs12570849	6e-07	FRMD4A	C	3.26
rs1020096	8e-07	LINC02676 - LINC00709	A	3.39
rs1024843	1e-06	PTPRO	T	3.03
rs2788869	1e-06	SYCP2L	A	3.22
rs1225763	2e-06	SYCP2L	A	3.34
rs1443267	3e-06	RN7SKP94 - MRPS23	A	2.75
rs2395166	3e-06	TSBP1-AS1 - HLA-DRA	T	2.56
rs145365907	4e-06	NGF-AS1 - ELOCP20	T	5.97
rs10886503	5e-06	GRK5 - RGS10	T	3.16
rs12153263	6e-06	CDH18	T	2.63
rs181132	6e-06	LINC00299	T	2.63
rs6477918	8e-06	PTBP3 - RPL32P22	C	2.15
rs35176804	9e-06	LINC01173 - SH3BP4	A	2.57

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004227	Sugiura-Ogasawara M	2017	115	0	The first genome-wide association study identifying new susceptibility loci for obstetric antiphospholipid syndrome.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	12

MAF distribution

Bucket	Variants
common (>=0.05)	13
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	7
intergenic_variant	5
3_prime_UTR_variant	1
splice_donor_5th_base_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs79154414	2	67897074	C>T	0.01	intergenic_variant	LINC01812 - FBXL12P1	5e-08	Tier 4: intronic/intergenic
rs2288493	14	81145262	C>T	0.24	3_prime_UTR_variant	TSHR-AS1, TSHR	8e-08	Tier 2: splice/UTR
rs12570849	10	14147601	T>C	0.05	intron_variant	FRMD4A	6e-07	Tier 4: intronic/intergenic
rs1020096	10	9224905	G>A,T	0.36	intron_variant	LINC02676 - LINC00709	8e-07	Tier 4: intronic/intergenic
rs1024843	12	15578810	C>A,T	0.3	intron_variant	PTPRO	1e-06	Tier 4: intronic/intergenic
rs2788869	6	10918280	G>A	0.05	intron_variant	SYCP2L	1e-06	Tier 4: intronic/intergenic
rs1225763	6	10924010	G>A,T	0.053	intron_variant	SYCP2L	2e-06	Tier 4: intronic/intergenic
rs1443267	17	57834081	A>C,G,T	0.13	intron_variant	RN7SKP94 - MRPS23	3e-06	Tier 4: intronic/intergenic
rs2395166	6	32420498	C>A,T	0.29	intron_variant	TSBP1-AS1 - HLA-DRA	3e-06	Tier 4: intronic/intergenic
rs145365907	1	115415802	A>T	0.01	intergenic_variant	NGF-AS1 - ELOCP20	4e-06	Tier 4: intronic/intergenic
rs10886503	10	119496237	T>A,C,G	0.39	intergenic_variant	GRK5 - RGS10	5e-06	Tier 4: intronic/intergenic
rs12153263	5	20300723	T>C	0.4	intergenic_variant	CDH18	6e-06	Tier 4: intronic/intergenic
rs181132	2	8143059	T>A,C	0.41	splice_donor_5th_base_variant	LINC00299	6e-06	Tier 2: splice/UTR
rs6477918	9	112356681	G>A,C	0.16	intergenic_variant	PTBP3 - RPL32P22	8e-06	Tier 4: intronic/intergenic
rs35176804	2	234906030	G>A	0.14	regulatory_region_variant	LINC01173 - SH3BP4	9e-06	Tier 3: regulatory

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSHR	Orphanet:424	Familial hyperthyroidism due to mutations in TSH receptor
TSHR	Orphanet:90673	Hypothyroidism due to TSH receptor mutations
TSHR	Orphanet:95713	Athyreosis
TSHR	Orphanet:95720	Thyroid hypoplasia
TSHR	Orphanet:99819	Familial gestational hyperthyroidism
FRMD4A	Orphanet:466688	Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome
GATA3	Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3	Orphanet:585936	B-lymphoblastic leukemia/lymphoma with hyperdiploidy
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome
NGF	Orphanet:64752	Hereditary sensory and autonomic neuropathy type 5

Cohort genes → proteins

14 cohort genes, 14 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PTBP3	HGNC:10253	ENSG00000119314	O95758	Polypyrimidine tract-binding protein 3	gwas
SH3BP4	HGNC:10826	ENSG00000130147	Q9P0V3	SH3 domain-binding protein 4	gwas
TSHR	HGNC:12373	ENSG00000165409	P16473	Thyrotropin receptor	gwas
MRPS23	HGNC:14509	ENSG00000181610	Q9Y3D9	Small ribosomal subunit protein mS23	gwas
CDH18	HGNC:1757	ENSG00000145526	Q13634	Cadherin-18	gwas
SYCP2L	HGNC:21537	ENSG00000153157	Q5T4T6	Synaptonemal complex protein 2-like	gwas
FRMD4A	HGNC:25491	ENSG00000151474	Q9P2Q2	FERM domain-containing protein 4A	gwas
LINC00299	HGNC:27940	ENSG00000236790	Q6ZSB3	Putative uncharacterized protein encoded by LINC00299	gwas
C1D	HGNC:29911	ENSG00000197223	Q13901	Nuclear nucleic acid-binding protein C1D	gwas
GATA3	HGNC:4172	ENSG00000107485	P23771	Trans-acting T-cell-specific transcription factor GATA-3	gwas
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	gwas
NGF	HGNC:7808	ENSG00000134259	P01138	Beta-nerve growth factor	gwas
PTPRU	HGNC:9683	ENSG00000060656	Q92729	Receptor-type tyrosine-protein phosphatase U	gwas
RGS10	HGNC:9992	ENSG00000148908	O43665	Regulator of G-protein signaling 10	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTBP3	Polypyrimidine tract-binding protein 3	RNA-binding protein that mediates pre-mRNA alternative splicing regulation.
SH3BP4	SH3 domain-binding protein 4	May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis.
TSHR	Thyrotropin receptor	Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin.
CDH18	Cadherin-18	Cadherins are calcium-dependent cell adhesion proteins.
SYCP2L	Synaptonemal complex protein 2-like	Oocyte-specific protein that localizes to centromeres at the dictyate stage and regulates the survival of primordial oocytes.
FRMD4A	FERM domain-containing protein 4A	Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex.
C1D	Nuclear nucleic acid-binding protein C1D	Plays a role in the recruitment of the RNA exosome complex to pre-rRNA to mediate the 3’-5’ end processing of the 5.8S rRNA; this function may include MPHOSPH6.
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.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
NGF	Beta-nerve growth factor	Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems.
PTPRU	Receptor-type tyrosine-protein phosphatase U	Tyrosine-protein phosphatase which dephosphorylates CTNNB1.
RGS10	Regulator of G-protein signaling 10	Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the muscarinic acetylcholine receptor CHRM2.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 9 · Druggable fraction: 0.21

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
Phosphatase	1	6.0×	0.675
Antibody/Immunoglobulin	1	2.1×	0.675
GPCR	1	1.7×	0.675
Other/Unknown	9	1.1×	0.675
Scaffold/PPI	1	1.2×	0.679
Transcription factor	1	0.6×	0.836

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTBP3	Other/Unknown	no		RRM_dom, HnRNP-L/PTB, Nucleotide-bd_a/b_plait_sf
SH3BP4	Scaffold/PPI	no		ZU5_dom, SH3_domain, SH3BP4_SH3
TSHR	GPCR	yes		GPCR_Rhodpsn, Gphrmn_rcpt_fam, TSH_rcpt
MRPS23	Other/Unknown	no		Ribosomal_mS23_met, mS23_dom_met, mS23_dom
CDH18	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
SYCP2L	Other/Unknown	no		SYCP2-like, SYCP2_SLD, SYCP2_ARLD
FRMD4A	Other/Unknown	no		FERM_domain, PH-like_dom_sf, FERM/acyl-CoA-bd_prot_sf
LINC00299	Other/Unknown	no
C1D	Other/Unknown	no		Sas10/Utp3/C1D, Exosome-assoc_fac/DNA_repair
GATA3	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3
HLA-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
NGF	Other/Unknown	no		Nerve_growth_factor-rel, Nerve_growth_factor_CS, Nerve_growth_factor-like
PTPRU	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, MAM_dom
RGS10	Other/Unknown	no		RGS, RGS_subdom1/3, RGS_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	3
monocyte	3
epithelium of nasopharynx	1
gingival epithelium	1
nasopharynx	1
mucosa of paranasal sinus	1
parotid gland	1
trachea	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1
cardiac ventricle	1
heart left ventricle	1
left ventricle myocardium	1
cerebellar vermis	1
middle temporal gyrus	1
paraflocculus	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTBP3	281	ubiquitous	marker	epithelium of nasopharynx, nasopharynx, gingival epithelium
SH3BP4	274	ubiquitous	marker	parotid gland, trachea, mucosa of paranasal sinus
TSHR	169	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
MRPS23	260	ubiquitous	marker	left ventricle myocardium, heart left ventricle, cardiac ventricle
CDH18	170	broad	marker	middle temporal gyrus, cerebellar vermis, paraflocculus
SYCP2L	161	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, primordial germ cell in gonad
FRMD4A	272	ubiquitous	marker	sural nerve, ganglionic eminence, oocyte
LINC00299	157	broad	marker	granulocyte, bone marrow cell, adrenal tissue
C1D	133	ubiquitous	marker	islet of Langerhans, monocyte, leukocyte
GATA3	220	broad	marker	upper leg skin, skin of hip, endometrium epithelium
HLA-DRA	132	broad	marker	monocyte, leukocyte, vermiform appendix
NGF	158	broad	marker	cartilage tissue, left uterine tube, right ovary
PTPRU	239	ubiquitous	marker	endocervix, olfactory segment of nasal mucosa, ectocervix
RGS10	276	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA3	5,990
NGF	3,968
HLA-DRA	3,244
MRPS23	2,232
PTBP3	1,820
C1D	1,809
TSHR	1,672
SH3BP4	1,247
RGS10	1,136
CDH18	889

Structural data

PDB: 7 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRA	P01903	140
MRPS23	Q9Y3D9	76
NGF	P01138	10
TSHR	P16473	9
GATA3	P23771	3
RGS10	O43665	3
PTPRU	Q92729	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C1D	Q13901	88.37
CDH18	Q13634	77.57
PTBP3	O95758	70.48
SH3BP4	Q9P0V3	70.15
SYCP2L	Q5T4T6	66.45
FRMD4A	Q9P2Q2	62.95
LINC00299	Q6ZSB3	33.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 58. Enrichment computed across 14 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TRKA activation by NGF	1	571.0×	0.029	NGF
NFG and proNGF binds to p75NTR	1	571.0×	0.029	NGF
PLC-gamma1 signalling	1	380.7×	0.029	NGF
Ceramide signalling	1	380.7×	0.029	NGF
Signalling to STAT3	1	380.7×	0.029	NGF
NGF processing	1	285.5×	0.029	NGF
Axonal growth stimulation	1	285.5×	0.029	NGF
Signalling to p38 via RIT and RIN	1	228.4×	0.030	NGF
p75NTR negatively regulates cell cycle via SC1	1	190.3×	0.030	NGF
NADE modulates death signalling	1	190.3×	0.030	NGF
ARMS-mediated activation	1	163.1×	0.032	NGF
PI3K/AKT activation	1	126.9×	0.038	NGF
Frs2-mediated activation	1	95.2×	0.041	NGF
Hormone ligand-binding receptors	1	95.2×	0.041	TSHR
p75NTR recruits signalling complexes	1	87.8×	0.041	NGF
NF-kB is activated and signals survival	1	87.8×	0.041	NGF
Retrograde neurotrophin signalling	1	81.6×	0.041	NGF
Developmental Lineage of Mammary Stem Cells	1	76.1×	0.041	GATA3
NRIF signals cell death from the nucleus	1	71.4×	0.041	NGF
Signalling to RAS	1	67.2×	0.041	NGF
Translocation of ZAP-70 to Immunological synapse	1	63.4×	0.041	HLA-DRA
Formation of the nephric duct	1	63.4×	0.041	GATA3
Phosphorylation of CD3 and TCR zeta chains	1	54.4×	0.046	HLA-DRA
Co-inhibition by PD-1	1	51.9×	0.046	HLA-DRA
Generation of second messenger molecules	1	34.6×	0.066	HLA-DRA
Nuclear RNA decay	1	30.9×	0.071	C1D
Signaling by SCF-KIT	1	24.8×	0.079	PTPRU
Adherens junctions interactions	1	24.8×	0.079	CDH18
Cell-cell junction organization	1	24.8×	0.079	CDH18
Amino acids regulate mTORC1	1	20.0×	0.094	SH3BP4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of T-helper cell differentiation	2	648.1×	7e-04	GATA3, HLA-DRA
type IV hypersensitivity	1	1296.3×	0.015	GATA3
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	1296.3×	0.015	HLA-DRA
thyroid-stimulating hormone signaling pathway	1	1296.3×	0.015	TSHR
cellular response to thyrotropin-releasing hormone	1	1296.3×	0.015	TSHR
obsolete negative regulation of cell proliferation involved in mesonephros development	1	1296.3×	0.015	GATA3
regulation of cellular response to X-ray	1	1296.3×	0.015	GATA3
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in ureteric bud formation	1	1296.3×	0.015	GATA3
obsolete negative regulation of glial cell-derived neurotrophic factor receptor signaling pathway involved in ureteric bud formation	1	1296.3×	0.015	GATA3
negative regulation of cell population proliferation	4	13.0×	0.015	SH3BP4, GATA3, NGF, PTPRU
antigen processing and presentation of endogenous peptide antigen via MHC class II	1	648.1×	0.022	HLA-DRA
pro-T cell differentiation	1	648.1×	0.022	GATA3
parathyroid hormone secretion	1	648.1×	0.022	GATA3
regulation of nephron tubule epithelial cell differentiation	1	648.1×	0.022	GATA3
myeloid dendritic cell antigen processing and presentation	1	432.1×	0.024	HLA-DRA
positive regulation of neuron maturation	1	432.1×	0.024	NGF
thymic T cell selection	1	432.1×	0.024	GATA3
nephric duct formation	1	432.1×	0.024	GATA3
cellular response to glycoprotein	1	432.1×	0.024	TSHR
immune system development	1	324.1×	0.025	GATA3
ureter maturation	1	324.1×	0.025	GATA3
mast cell differentiation	1	324.1×	0.025	GATA3
positive regulation of CD4-positive, alpha-beta T cell activation	1	324.1×	0.025	HLA-DRA
positive regulation of thyroid hormone generation	1	324.1×	0.025	GATA3
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1	259.3×	0.026	HLA-DRA
negative regulation of mammary gland epithelial cell proliferation	1	259.3×	0.026	GATA3
regulation of catalytic activity	1	259.3×	0.026	SH3BP4
nephric duct morphogenesis	1	259.3×	0.026	GATA3
anatomical structure morphogenesis	2	21.4×	0.026	PTBP3, GATA3
otic vesicle development	1	216.1×	0.030	GATA3

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Hydroxychloroquine	Phase 3 (in late-stage trials)

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

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 13

Druggability breadth: 5 of 14 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
TSHR	LEVOSALBUTAMOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSHR	354	4
PTBP3	0	0
SH3BP4	0	0
MRPS23	0	0
CDH18	0	0
SYCP2L	0	0
FRMD4A	0	0
LINC00299	0	0
C1D	0	0
GATA3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEVOSALBUTAMOL	4	TSHR
PROGESTERONE	4	TSHR
DICLOFENAC SODIUM	4	TSHR
CLOTRIMAZOLE	4	TSHR
DAPSONE	4	TSHR
COLCHICINE	4	TSHR
OXAPROZIN	4	TSHR
BUMETANIDE	4	TSHR
GLIPIZIDE	4	TSHR
CARBAMAZEPINE	4	TSHR
METHYL SALICYLATE	4	TSHR
PHENELZINE	4	TSHR
EDROPHONIUM	4	TSHR
SULFAPHENAZOLE	4	TSHR
AMOXAPINE	4	TSHR
PYRIDOSTIGMINE	4	TSHR
ACETAMINOPHEN	4	TSHR
DICYCLOMINE	4	TSHR
IODIPAMIDE	4	TSHR
TESTOSTERONE PROPIONATE	4	TSHR
TETRABENAZINE	4	TSHR
CELECOXIB	4	TSHR
PROPANTHELINE	4	TSHR
BENOXINATE	4	TSHR
NICARDIPINE HYDROCHLORIDE	4	TSHR
PYRITHIONE ZINC	4	TSHR
GUANABENZ ACETATE	4	TSHR
PROPIOLACTONE	4	TSHR
CHLOROTRIANISENE	4	TSHR
PHENOXYBENZAMINE HYDROCHLORIDE	4	TSHR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TSHR	33	Functional:24, Binding:9
NGF	4	Binding:4
MRPS23	2	Binding:2
PTBP3	1	Binding:1
PTPRU	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPRU	3.1.3.48	protein-tyrosine-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
LEVOSALBUTAMOL	4	TSHR
PROGESTERONE	4	TSHR
DICLOFENAC SODIUM	4	TSHR
CLOTRIMAZOLE	4	TSHR
DAPSONE	4	TSHR
COLCHICINE	4	TSHR
OXAPROZIN	4	TSHR
BUMETANIDE	4	TSHR
GLIPIZIDE	4	TSHR
CARBAMAZEPINE	4	TSHR
METHYL SALICYLATE	4	TSHR
PHENELZINE	4	TSHR
EDROPHONIUM	4	TSHR
SULFAPHENAZOLE	4	TSHR
AMOXAPINE	4	TSHR
PYRIDOSTIGMINE	4	TSHR
DICYCLOMINE	4	TSHR
IODIPAMIDE	4	TSHR
TESTOSTERONE PROPIONATE	4	TSHR
TETRABENAZINE	4	TSHR
CELECOXIB	4	TSHR
PROPANTHELINE	4	TSHR
BENOXINATE	4	TSHR
NICARDIPINE HYDROCHLORIDE	4	TSHR
PYRITHIONE ZINC	4	TSHR
GUANABENZ ACETATE	4	TSHR
PROPIOLACTONE	4	TSHR
CHLOROTRIANISENE	4	TSHR
PHENOXYBENZAMINE HYDROCHLORIDE	4	TSHR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TSHR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	HLA-DRA, PTPRU
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	11	PTBP3, SH3BP4, MRPS23, CDH18, SYCP2L, FRMD4A, LINC00299, C1D, GATA3, NGF (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTBP3	1	—
SH3BP4	0	—
MRPS23	2	—
CDH18	0	—
SYCP2L	0	—
FRMD4A	0	—
LINC00299	0	—
C1D	0	—
GATA3	0	—
HLA-DRA	0	—
NGF	4	—
PTPRU	1	—
RGS10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 98.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	59
PHASE2	12
PHASE1	10
PHASE4	9
PHASE3	3
PHASE1/PHASE2	2
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05995600	PHASE4	RECRUITING	Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE
NCT07087912	PHASE4	RECRUITING	Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
NCT01104337	PHASE4	COMPLETED	Drug Interaction Between Paracetamol and Warfarin
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT02116036	PHASE4	COMPLETED	Rivaroxaban for Antiphospholipid Antibody Syndrome
NCT02295475	PHASE4	COMPLETED	Apixaban for Secondary Prevention of Thromboembolism Among Patients With AntiphosPholipid Syndrome
NCT02303171	PHASE4	UNKNOWN	Use of Warfarin After the First Trimester in Pregnant Women With APS
NCT02326051	PHASE4	COMPLETED	Timing of Initiation of LMWH Administration in Pregnant Women With APS
NCT04624269	PHASE4	UNKNOWN	A Study of Hydroxychloroquine Sulfate in the Treatment of Recurrent Spontaneous Abortion With Antiphospholipid Syndrome
NCT01784523	PHASE3	TERMINATED	Hydroxychloroquine for the First Thrombosis Prevention in Antiphospholipid Antibody Positive Patients
NCT02157272	PHASE3	TERMINATED	Rivaroxaban in Thrombotic Antiphospholipid Syndrome
NCT02926170	PHASE3	COMPLETED	Rivaroxaban for Patients With Antiphospholipid Syndrome
NCT05020782	PHASE2/PHASE3	UNKNOWN	The BeLimumab Antiphospholipid Syndrome Trial (BLAST)
NCT05199909	PHASE2	RECRUITING	Safety and Efficacy of Zanubrutinib in the Treatment of Antiphospholipid Syndrome With Secondary Thrombocytopenia
NCT05983952	PHASE2	RECRUITING	Anti-CD38 Antibody Treating APS With Thrombocytopenia
NCT06747312	PHASE2	RECRUITING	Effect of Belimumab on Antibody Titers in Primary APS Patients
NCT06794008	PHASE2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT06828042	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of Universal CD19-targeting CAR-γδT Cells in Refractory Autoimmune Diseases
NCT07584083	PHASE2	NOT_YET_RECRUITING	Anifrolumab in Adults With Primary Antiphospholipid Syndrome (AnifAPS Trial)
NCT00180778	PHASE1/PHASE2	WITHDRAWN	Steroids and Antiphospholipid Syndrome- Related Pregnancy Loss
NCT00537290	PHASE2	COMPLETED	A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome
NCT00674297	PHASE2	COMPLETED	Effects of Fluvastatin on Proinflammatory and Prothrombotic Markers in Antiphospholipid Syndrome Patients
NCT01029587	PHASE2	COMPLETED	Eculizumab to Enable Renal Transplantation in Patients With History of Catastrophic Antiphospholipid Antibody Syndrome
NCT02595346	PHASE2	TERMINATED	Study of the Efficiency of Hydroxychloroquine on the Endothelial Dysfunction and Its Vascular Consequences During the Antiphospholipid Syndrome
NCT03684564	PHASE2	COMPLETED	RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome
NCT06315530	PHASE2	COMPLETED	Effect of Telitacicept on Antibody Titers in Primary APS Patients
NCT07172022	PHASE2	WITHDRAWN	A Study to Evaluate Crovalimab in People With Antiphospholipid Syndrome (APS)
NCT06371417	PHASE1	RECRUITING	Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
NCT06723106	PHASE1	ENROLLING_BY_INVITATION	Phase 1b Long-term Extension Trial of RAY121 in Immunological Diseases (RAINBOW-LTE Trial)
NCT06978647	PHASE1	RECRUITING	A Clinical Study of YTS109 Cell in R/R Autoimmune Diseases
NCT07085676	PHASE1	RECRUITING	Phase 1 Study of HBI0101 CAR-T in Refractory B-Cell Autoimmune Diseases
NCT07104721	PHASE1	RECRUITING	A Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
NCT07123519	PHASE1	RECRUITING	A Clinical Study of YTS109 Cells for the Treatment of R/R Autoimmune Diseases
NCT07236762	PHASE1	RECRUITING	An Exploratory Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
NCT07236801	PHASE1	RECRUITING	Exploratory Clinical Study on YTS109 Cell Therapy for Autoimmune Diseases
NCT07439029	PHASE1	NOT_YET_RECRUITING	YTS109 in Pediatric Relapsed/Refractory Autoimmune Diseases
NCT00278616	PHASE1	WITHDRAWN	Hematopoietic Stem Cell Transplantation in Patients With Antiphospholipid Syndrome
NCT06420154	EARLY_PHASE1	NOT_YET_RECRUITING	The Safety and Efficacy of Anti-CD19 CAR-T Cells in Patients With Relapsed/Refractory Autoimmune Diseases
NCT07301164	EARLY_PHASE1	NOT_YET_RECRUITING	Clinical Study of BCT301 Cell Injection Therapy for Refractory Autoimmune Diseases
NCT00198068	Not specified	RECRUITING	Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HYDROXYCHLOROQUINE	4	3
WARFARIN	4	3
ACETAMINOPHEN	4	2
BELIMUMAB	4	2
ENOXAPARIN SODIUM	4	2
ACENOCOUMAROL	4	1
ANIFROLUMAB	4	1
APIXABAN	4	1
CROVALIMAB	4	1
ECULIZUMAB	4	1
FLUVASTATIN	4	1
RIVAROXABAN	4	1
ROFECOXIB	4	1
ZANUBRUTINIB	4	1
TELITACICEPT	3	2
ENOXAPARIN	0	2
CHEMBL5592090	0	1
CHEMBL350239	0	1
CHEMBL4781824	0	1
CHEMBL5193128	0	1