Atypical hemolytic-uremic syndrome

Summary

Atypical hemolytic-uremic syndrome (MONDO:0016244) is a disease caused by CFI (GenCC Definitive), with 33 cohort genes and 40 clinical trials. The dominant Reactome pathway is Regulation of Complement cascade (11 cohort genes). Top therapeutic interventions include eculizumab, ravulizumab, and crovalimab.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: CFI (GenCC Definitive)
• Cohort genes: 33
• ClinVar variants: 1,216
• Phenotypes (HPO): 13
• Clinical trials: 40

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.2	United States	Validated
Point prevalence	<1 / 1 000 000	0.0278	China	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000093	Proteinuria	Very frequent (80-99%)
HP:0000790	Hematuria	Very frequent (80-99%)
HP:0001871	Abnormality of blood and blood-forming tissues	Very frequent (80-99%)
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0001919	Acute kidney injury	Very frequent (80-99%)
HP:0001937	Microangiopathic hemolytic anemia	Very frequent (80-99%)
HP:0001939	Abnormality of metabolism/homeostasis	Very frequent (80-99%)
HP:0045040	Abnormal lactate dehydrogenase activity	Very frequent (80-99%)
HP:0004431	Complement deficiency	Frequent (30-79%)
HP:0005339	Abnormality of complement system	Frequent (30-79%)
HP:0005356	Decreased serum complement factor I	Frequent (30-79%)
HP:0005416	Decreased serum complement factor B	Frequent (30-79%)
HP:0040229	Decreased level of thrombomodulin	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	atypical hemolytic-uremic syndrome
Mondo ID	MONDO:0016244
MeSH	D065766
Orphanet	2134
DOID	DOID:0080301
NCIT	C123223
UMLS	C2931788
MedGen	444141
GARD	0008702
NORD	822
Is cancer (heuristic)	no

Also known as: aHUS · Atypical Hemolytic Uremic Syndrome · atypical hemolytic uremic syndrome · atypical HUS · D-HUS · D-minus hemolytic uremic syndrome (D-HUS) · hemolytic-uremic syndrome without diarrhea · hemolytic-uremic syndrome without diarrhoea · HUS, atypical · non-diarrhea-associated hemolytic uremic syndrome

Data availability: 1,216 ClinVar variants · 2 GenCC gene-disease records · 6 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › atypical hemolytic-uremic 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, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, infantile spasms, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, Usher syndrome, obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome, CREST syndrome, Sheehan syndrome, polymyalgia rheumatica, autoinflammatory syndrome, neuroleptic malignant syndrome, pituitary stalk interruption syndrome, monosomy 13q34, ring chromosome 13, 48,XXXY syndrome, 49,XXXXY syndrome, hereditary continuous muscle fiber activity, Eisenmenger syndrome, Robinow syndrome, Ehlers-Danlos syndrome, hypoplastic right heart syndrome, shone complex, 48,XYYY syndrome, subcortical band heterotopia, complex regional pain syndrome type 2, faciodigitogenital syndrome, neoplastic syndrome, paraneoplastic syndrome, post-infectious syndrome, Achard-Thiers syndrome, acral dysostosis dyserythropoiesis syndrome, agnathia-microstomia-synotia, Aksu von Stockhausen syndrome, Aloi Tomasini Isaia syndrome, temporomandibular joint dysfunction syndrome, Apert-like polydactyly syndrome, arakawa syndrome 2, arena syndrome, Arnold stickler bourne syndrome, baetz-greenwalt syndrome, bagatelle Cassidy syndrome, baker Vinters syndrome, bobble-head doll syndrome, Boerhaave syndrome, Cantu Sanchez-Corona Fragoso syndrome, Cantu Sanchez-Corona Hernandez syndrome, carbon baby syndrome, Carnevale hernandez castillo syndrome, Cartwright Nelson Fryns syndrome, Charles bonnet syndrome, Parinaud syndrome, corticobasal degeneration disorder, hair defect with photosensitivity and intellectual disability syndrome, AIDS dysmorphic syndrome, congenital acardia, acute lymphoblastic leukemia congenital sporadic aniridia, aglossia and situs inversus, agyria pachygyria polymicrogyria, agyria-pachygyria type 1, Ahumada Del Castillo syndrome, alopecia congenita keratosis palmoplantaris, alpha-mannosidosis type 1, aluminosis, Mauriac syndrome, ankle defects short stature, ankyloblepharon filiforme imperforate anus, annular constricting bands, anophthalmia cleft palate micrognathia, anophthalmia esophageal atresia cryptorchidism, anotia facial palsy cardiac defect, aortic dissection lentiginosis, childhood aortic valve stenosis, arthrogryposis IUGR thoracic dystrophy, arthrogryposis multiplex congenita CNS calcification, arthrogryposis spinal muscular atrophy, asternia, atlanto-axial fusion, atrophoderma of Pierini and Pasini, Barnicoat Baraitser syndrome, Basedow’s coma, BD syndrome, Beardwell syndrome, bhaskar jagannathan syndrome, bidirectional tachycardia, bilirubin induced brain injury in the newborn, blepharo naso facial syndrome van Maldergem type, bone dysplasia corpus callosum agenesis, brachydactyly absence of distal phalanges, brachydactyly anonychia, brachydactyly small stature face anomalies, brachydactyly tibial hypoplasia, brittle bone syndrome lethal type, bronchiectasis oligospermia, Brunsting-Perry syndrome, bruyn scheltens syndrome, burn goodship syndrome, camptodactyly joint contractures and facial skeletal dysplasia, camptodactyly vertebral fusion, Cantu Sanchez-Corona Garcia-Cruz syndrome, cardiac hydatid cysts with intracavitary expansion, cardioencephalomyopathy, cardiofacial syndrome short limbs, cardiomelic syndrome stratton Koehler type, cardiomyopathy and deafness due to tRNA lysine gene mutation, cardiomyopathy diabetes deafness, cardiomyopathy hypogonadism collagenoma syndrome, cardiomyopathy hypogonadism metabolic anomalies, cardiomyopathy spherocytosis, carpo tarsal osteolysis recessive, autosomal dominant cataract, cataract skeletal anomalies, cennamo gangemi syndrome, cerebellar agenesis, cerebello-olivary atrophy, cerebral calcification cerebellar hypoplasia, cerebral calcifications opalescent teeth phosphaturia, oculo digital syndrome, chondrodysplasia, choreoacanthocytosis amyotrophic, chorioretinopathy dominant form microcephaly, Christian Demyer Franken syndrome, Christian Johnson angenieta syndrome, chromosome 3 duplication syndrome, chronic demyelinizing neuropathy with IgM monoclonal, ciliary dyskinesia-bronchiectasis, circumscribed cutaneous aplasia of the vertex, circumscribed disseminated keratosis Jadassohn lew type, cleft lip and palate malrotation cardiopathy, cleft lip and/or palate with mucous cysts of lower, cleft lip palate dysmorphism kumar type, cleft lip palate intellectual disability corneal opacity, cleft lip palate oligodontia syndactyly pili torti, cleft lip palate pituitary deficiency, cleft lip palate-tetraphocomelia, cleft lower lip cleft lateral canthi chorioretinal, cleft palate cardiac defect ectrodactyly, cleft palate colobomata radial synostosis deafness, cleft palate heart disease polydactyly absent tibia, cleft tongue, coarse face hypotonia constipation, Cohen Lockood Wyborney syndrome, type 2 collagenopathy, Collins-Sakati syndrome, coloboma porencephaly hydronephrosis, colobomata unilobar lung heart defect, colonic malakoplakia, Colver Steer Godman syndrome, Combarros Calleja Leno syndrome, complement receptor deficiency, congenital absence of the sternocleidomastoid muscle, congenital amputation, congenital aneurysms of the great vessels, congenital articular rigidity, congenital benign spinal muscular atrophy dominant, congenital cardiovascular shunt, congenital contractures, congenital craniosynostosis maternal hyperthyroiditis, congenital cystic eye, congenital heart disease ptosis hypodontia craniostosis, congenital heart disease radio ulnar synostosis intellectual disability, congenital mumps, congenital stenosis of cervical medullary canal, Dennis-Fairhurst-Moore syndrome, congenital unilateral pulmonary hypoplasia, congenital vagal hyperreflexivity, Cormier Rustin Munnich syndrome, corneal crystals myopathy neuropathy, corneal dystrophy ichthyosis microcephaly intellectual disability, corneal dystrophy pigmentary anomaly malabsorption, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cortada Koussef Matsumoto syndrome, Cortes Lacassie syndrome, craniofacial and skeletal defects, craniofacial dysostosis arthrogryposis progeroid appearance, craniofrontonasal syndrome Teebi type, craniostenosis with congenital heart disease intellectual disability, crawfurd syndrome, cutis gyratum acanthosis nigricans craniosynostosis, cutis laxa osteoporosis, Davenport-Donlan syndrome, Davis Lafer syndrome, de Hauwere Leroy adriaenssens syndrome, deafness conductive stapedial ear malformation facial palsy, deafness goiter stippled epiphyses, deafness hypospadias metacarpal and metatarsal syndrome, deafness mesenteric diverticula of small bowel neuropathy, deafness peripheral neuropathy arterial disease, deafness progressive cataract autosomal dominant, dermatocardioskeletal syndrome boronne type, dextrocardia with situs inversus, diabetes persistent mullerian ducts, diaphragmatic agenesis radial aplasia omphalocele, diaphragmatic hernia exomphalos corpus callosum agenesis, diaphragmatic hernia upper limb defects, die Smulders droog van dijk syndrome, diomedi bernardi placidi syndrome, diphallus rachischisis imperforate anus, distichiasis heart congenital anomalies, double discordia, double uterus-hemivagina-renal agenesis, Drachtman Weinblatt Sitarz syndrome, Duker-Weiss-Siber syndrome, duodenal atresia tetralogy of fallot, duplication of leg mirror foot, duplication of the thumb unilateral biphalangeal, dupont sellier chochillon syndrome, dwarfism bluish sclerae, dwarfism deafness retinitis pigmentosa, dwarfism lethal type advanced bone age, dwarfism thin bones multiple fractures, dysmorphism cleft palate loose skin, Eagle syndrome, ectrodactyly cardiopathy dysmorphism, Elliott ludman Teebi syndrome, enamel hypoplasia cataract hydrocephaly, encephalocele anencephaly, enchondromatosis dwarfism deafness, Engelhard Yatziv syndrome, enlarged vestibular aqueduct syndrome, epidermal nevus vitamin D resistant rickets, epimetaphyseal dysplasia cataract, epiphyseal dysplasia dysmorphism camptodactyly, esophageal atresia coloboma talipes, extrasystoles short stature hyperpigmentation microcephaly, facial clefting corpus callosum agenesis, facio digito genital syndrome recessive form, facio skeletal genital syndrome rippberger type, familial capillaro-venous leptomeningeal angiomatosis, Dursun syndrome, Faye-Petersen-Ward-Carey syndrome, feigenbaum Bergeron syndrome, Feingold trainer syndrome, fetal brain disruption sequence, fetal enterovirus syndrome, fetal parainfluenza virus type 3 syndrome, fetal phenothiazine syndrome, fibromatosis multiple non ossifying, fibula aplasia complex brachydactyly, fibular hypoplasia scapulo pelvic dysplasia absent, Fitz-Hugh-Curtis syndrome, focal alopecia congenital megalencephaly, focal or multifocal malformations in neuronal migration, foix chavany Marie syndrome, Fontaine farriaux blanckaert syndrome, Fraser Jequier Chen syndrome, Freiberg disease, Friedman Goodman syndrome, frontonasal malformation cloacal exstrophy, frontonasal dysplasia Klippel feil syndrome, frontonasal dysplasia phocomelic upper limbs, Fryns Fabry Remans syndrome, Fryns Smeets Thiry syndrome, Fuchs atrophia gyrata chorioideae et retinae, Fukuda-Miyanomae-Nakata syndrome, Fuqua Berkovitz syndrome, Garret-Tripp syndrome, gas bloat syndrome, Gaucher ichthyosis restrictive dermopathy, gershinibaruch Leibo syndrome, Ghose-Sachdev-Kumar syndrome, gigantism advanced bone age hoarse cry, glossopalatine ankylosis micrognathia ear anomalies, goldstein hutt syndrome, goniodysgenesis intellectual disability short stature, green sandford davison syndrome, grix Blankenship Peterson syndrome, Ho-Kaufman-McAlister syndrome, Jaffer-Beighton syndrome, Judge Misch wright syndrome, Kashani-Strom-Utley syndrome, Kasznica-Carlson-Coppedge syndrome, Katsantoni-Papadakou-Lagoyanni syndrome, Kocher-debre-Semelaigne syndrome, Koone-Rizzo-Elias syndrome, Kozlowski Brown Hardwick syndrome, Kozlowski Ouvrier syndrome, Kozlowski Rafinski Klicharska syndrome, Kozlowski Warren Fisher syndrome, Krauss Herman Holmes syndrome, Krieble Bixler syndrome, Kuster Majewski Hammerstein syndrome, Kuster syndrome, Laugier-Hunziker syndrome, Laurence-Prosser-Rocker syndrome, le Marec-Bracq-Picaud syndrome, levator syndrome, Marinesco-Sjogren-like syndrome, Milner-Khallouf-Gibson syndrome, radio-digito-facial dysplasia, Seckel like syndrome majoor-krakauer type, neonatal aspiration syndrome, muscular fibrosis multifocal obstructed vessels, short stature contractures hypotonia, Alice in Wonderland syndrome, megacystis-microcolon-intestinal hypoperistalsis syndrome, Basilicata-Akhtar syndrome, Liberfarb syndrome, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardiac, facial, and digital anomalies with developmental delay, fibrosis, neurodegeneration, and cerebral angiomatosis, Duane anomaly-myopathy-scoliosis syndrome, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, acute radiation syndrome, monoclonal mast cell activation syndrome, oculocerebrodental syndrome, syndromic congenital sodium diarrhea, congenital brachyesophagus-intrathoracic stomach-vertebral anomalies syndrome, intellectual disability-cardiac anomalies-short stature-joint laxity syndrome, intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome, frontonasal dysplasia-bifid nose-upper limb anomalies syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, diaphragmatic hernia-short bowel-asplenia syndrome, warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome, Cramp-fasciculation syndrome, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, blepharophimosis-intellectual disability syndrome/genitopatellar overlap syndrome, CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome, cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome, KLHL7-related Bohring-Opitz-like syndrome, KLHL7-related cold-induced sweating-like syndrome, KAT6B-related multiple congenital anomalies syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, Ruzicka-Goerz-Anton syndrome, Sammartino-Decreccio syndrome, Samson-Gardner syndrome, Samson-Viljoen syndrome, Sanderson-Fraser syndrome, Sandhaus-Ben-Ami syndrome, prostatic malacoplakia associated with prostatic abscess, Saul-Wilkes-Stevenson syndrome, macrogyria, pseudobulbar palsy and intellectual disability, Schwartz-Cohen-addad-Lambert syndrome, Schlegelberger-Grote syndrome, Schrander-stumpel-Theunissen-Hulsmans syndrome, Saal-Bulas syndrome, Sackey-Sakati-Aur syndrome, Slti-Salem syndrome, Zerres Rietschel Majewski syndrome, Zazam Sheriff Phillips syndrome, Zadik-Barak-Levin syndrome, weinstein kliman scully syndrome, thickened earlobes with conductive deafness from incus-stapes abnormalities, ichthyosis linearis circumflexa, infantile striato thalamic degeneration, Landy-Donnai syndrome, merlob grunebaum reisner syndrome, Pavone Fiumara Rizzo syndrome, pfeiffer rockelein syndrome, Pfeiffer Tietze Welte syndrome, phosphoribosylpyrophosphate synthetase deficiency, piepkorn karp hickok syndrome, podder-tolmie syndrome, pointer syndrome, richieri-costa guion-almeida cohen syndrome, Rubinstein Taybi like syndrome, ruvalcaba churesigaew myhre syndrome, short limb dwarf lethal colavita kozlowski type, Mallory-Weiss syndrome, superior vena cava syndrome, piriformis syndrome, engraftment syndrome, Adams-Stokes syndrome, Leriche syndrome, multiple organ dysfunction syndrome, posterior leukoencephalopathy syndrome, cardio-renal syndrome, Rahman syndrome, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, Lopes-Maciel-Rodan syndrome, Stankiewicz-Isidor syndrome, Skraban-Deardorff syndrome, joint laxity, short stature, and myopia, Sweeney-Cox syndrome, Alkuraya-Kucinskas syndrome, Jaberi-Elahi syndrome, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, hearing impairment and infertile male syndrome, cardiocutaneous syndrome, neonatal diabetes, congenital sensorineural hearing loss and congenital cataracts, cardioectodermal syndrome, cannabinoid hyperemesis syndrome, retrograde cricopharyngeus dysfunction, Zinner syndrome, retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome, IFAP syndrome, DICER1-related tumor predisposition, Roberts-SC phocomelia syndrome, carcinoid syndrome, Bonnevie-Ullrich syndrome, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, RNU4ATAC spectrum disorder, syndromic congenital heart disease, hand-foot syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, gastrointestinal defects and immunodeficiency syndrome 1, achalasia-alacrima syndrome, black locks with albinism and deafness syndrome, Birt-Hogg-Dube syndrome, trigeminal trophic syndrome, developmental and/or epileptic encephalopathy with spike-wave activation in sleep, syndromic microspherophakia, painful legs and moving toes syndrome, congenital aphakia-iris hypoplasia-microphthalmia-microcornea syndrome, hereditary persistence of fetal hemoglobin-intellectual disability syndrome, developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome, primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome, post-cardiac arrest syndrome, early-onset obesity-hyperphagia-severe developmental delay syndrome, hereditary alpha tryptasemia syndrome, KINSSHIP syndrome, developmental delay, hypotrophy, and dysmorphic features without moebius syndrome, breast implant illness, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, craniosynostosis-facial dysmorphism-chiari-1 malformation-developmental and language delay syndrome, MYT1L-related developmental delay-intellectual disability-obesity syndrome, Houge-Janssens syndrome, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, pyoderma gangrenosum-acne-hidradenitis suppurativa-ankylosing spondylitis syndrome, psoriatic arthritis-pyoderma gangrenosum-acne-hidradenitis suppurativa syndrome, megalencephaly-polydactyly syndrome, Leigh syndrome, mitochondrial, auroneurodental syndrome, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, Grisel syndrome, arterial tortuosity-bone fragility syndrome, dialysis disequilibrium syndrome, brain abnormalities-severe developmental delay-facial dysmorphism-intellectual disability syndrome due to MEF2C mutation, Kariminejad neurodevelopmental syndrome, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, Morimoto-Ryu-Malicdan neuromuscular syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, Pan-Chung-Bellen syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, Tayoun-Maawali syndrome, ragopathy, cardiovascular-kidney-metabolic syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Li-Takada-Miyake syndrome, Guillouet-Gordon syndrome, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, RAC2-related combined immunodeficiency-bronchiectasis-cancer-predisposing syndrome, oculovertebral syndrome, Alsahan-Harris syndrome, Ververi-Brady syndrome, Dursun-Ozgul neurodevelopmental syndrome, immune dysregulation, neurodevelopmental defects, and colitis, Harel-Tora neurodevelopmental syndrome, Valence-Farazi cerebellar ataxia syndrome, dyschromatosis, ichthyosis, deafness, and atopic disease, Ramond-Elliott neurodevelopmental syndrome, STAD syndrome, craniosynostosis-scoliosis syndrome, loin pain hematuria syndrome, IRF6-related condition, linkeropathy, NDUFB11-related disorders, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy, antiphospholipid syndrome

Subtypes (4): atypical hemolytic-uremic syndrome with DGKE deficiency, atypical hemolytic-uremic syndrome with H factor anomaly, atypical hemolytic-uremic syndrome with anti-factor H antibodies, atypical hemolytic uremic syndrome with complement gene abnormality

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

288 uncertain significance, 87 conflicting classifications of pathogenicity, 60 benign/likely benign, 57 benign, 22 pathogenic, 19 likely pathogenic, 18 pathogenic/likely pathogenic, 17 likely benign, 15 pathogenic, low penetrance, 6 likely pathogenic, low penetrance, 4 pathogenic/pathogenic, low penetrance, 2 likely pathogenic/likely pathogenic, low penetrance, 2 pathogenic/likely pathogenic/pathogenic, low penetrance, 2 likely pathogenic/pathogenic, low penetrance, 1 pathogenic/likely pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2506572	NM_001011551.3(C1GALT1C1):c.266C>T (p.Thr89Ile)	C1GALT1C1	Pathogenic	criteria provided, single submitter
1163121	NM_000064.4(C3):c.481C>T (p.Arg161Trp)	C3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17060	NM_000064.4(C3):c.1775G>A (p.Arg592Gln)	C3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1163188	NM_172351.3(CD46):c.286+1G>C	CD46	Pathogenic	criteria provided, multiple submitters, no conflicts
1163189	NM_172351.3(CD46):c.287-2A>G	CD46	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333461	NM_172351.3(CD46):c.350_351dup (p.Glu118fs)	CD46	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343345	NM_172351.3(CD46):c.820_821del (p.Ser274fs)	CD46	Pathogenic/Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
17044	NM_172351.3(CD46):c.800_801del (p.Thr267fs)	CD46	Pathogenic	criteria provided, single submitter
17047	NM_172351.3(CD46):c.98-1G>C	CD46	Pathogenic	criteria provided, single submitter
17048	NM_172351.3(CD46):c.175C>T (p.Arg59Ter)	CD46	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16080	NM_001710.6(CFB):c.967A>G (p.Lys323Glu)	CFB	Pathogenic	criteria provided, single submitter
2584501	NM_001710.6(CFB):c.856T>C (p.Phe286Leu)	CFB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4280404	NM_001710.6(CFB):c.1050G>C (p.Lys350Asn)	CFB	Pathogenic	criteria provided, single submitter
4280405	NM_001710.6(CFB):c.1050G>T (p.Lys350Asn)	CFB	Pathogenic	criteria provided, single submitter
4280406	NM_001710.6(CFB):c.1101C>G (p.Ser367Arg)	CFB	Pathogenic	criteria provided, single submitter
4280407	NM_001710.6(CFB):c.1101C>A (p.Ser367Arg)	CFB	Pathogenic	criteria provided, single submitter
4280408	NM_001710.6(CFB):c.1099A>C (p.Ser367Arg)	CFB	Pathogenic	criteria provided, single submitter
1068249	NM_000186.4(CFH):c.157C>T (p.Arg53Cys)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1162886	NM_000186.4(CFH):c.694C>T (p.Arg232Ter)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1163684	NM_000186.4(CFH):c.3356A>G (p.Asp1119Gly)	CFH	Likely pathogenic/Likely pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
1175202	NM_000186.4(CFH):c.3548G>T (p.Trp1183Leu)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343348	NM_000186.4(CFH):c.740del (p.Gly247fs)	CFH	Likely pathogenic/Likely pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
1343362	NM_000186.4(CFH):c.3493+1G>A	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1417726	NM_000186.4(CFH):c.213G>A (p.Trp71Ter)	CFH	Pathogenic/Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
1450348	NM_000186.4(CFH):c.1873G>T (p.Glu625Ter)	CFH	Pathogenic	criteria provided, multiple submitters, no conflicts
1452931	NM_000186.4(CFH):c.1243del (p.Ala415fs)	CFH	Pathogenic	criteria provided, multiple submitters, no conflicts
1493683	NM_000186.4(CFH):c.1520-1G>A	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16542	NM_000186.4(CFH):c.3643C>G (p.Arg1215Gly)	CFH	Pathogenic	criteria provided, single submitter
16545	NM_000186.4(CFH):c.3572C>T (p.Ser1191Leu)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16552	NM_000186.4(CFH):c.83_86del (p.Arg28fs)	CFH	Pathogenic, low penetrance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 73 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
CFI	Definitive	Autosomal dominant	atypical hemolytic-uremic syndrome	9
VTN	Limited	Autosomal dominant	atypical hemolytic-uremic syndrome

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFI	Orphanet:200418	Immunodeficiency with factor I anomaly
CFI	Orphanet:244242	HELLP syndrome
CFI	Orphanet:244275	De novo thrombotic microangiopathy after kidney transplantation
CFI	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
CFI	Orphanet:75376	Familial drusen
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
SMARCAL1	Orphanet:1830	Schimke immuno-osseous dysplasia
THBD	Orphanet:436169	Thrombomodulin-related bleeding disorder
THBD	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
TRPC6	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
C2	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
C3	Orphanet:280133	Complement component 3 deficiency
C3	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
ADAMTS13	Orphanet:93583	Congenital thrombotic thrombocytopenic purpura
NLRP3	Orphanet:1451	CINCA syndrome
NLRP3	Orphanet:47045	Familial cold urticaria
NLRP3	Orphanet:575	Muckle-Wells syndrome
NLRP3	Orphanet:647815	Keratitis fugax hereditaria
CFHR3	Orphanet:329931	C3 glomerulonephritis
NPHP4	Orphanet:3156	Senior-Loken syndrome
NPHP4	Orphanet:93592	Juvenile nephronophthisis
COL4A3	Orphanet:653722	Digenic Alport syndrome
COL4A3	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
COL4A3	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A3	Orphanet:88919	Autosomal recessive Alport syndrome
COL4A4	Orphanet:653722	Digenic Alport syndrome
COL4A4	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A4	Orphanet:88919	Autosomal recessive Alport syndrome
COL4A5	Orphanet:1018	X-linked Alport syndrome-diffuse leiomyomatosis
COL4A5	Orphanet:653722	Digenic Alport syndrome
COL4A5	Orphanet:88917	X-linked Alport syndrome
MMACHC	Orphanet:79282	Methylmalonic acidemia with homocystinuria, type cblC
CFHR5	Orphanet:329931	C3 glomerulonephritis
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
DGKE	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
DGKE	Orphanet:357008	Hemolytic uremic syndrome with DGKE deficiency
CEP290	Orphanet:110	Bardet-Biedl syndrome

Cohort genes → proteins

33 cohort genes, 31 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	33

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFI	HGNC:5394	ENSG00000205403	P05156	Complement factor I	gencc,clinvar
VTN	HGNC:12724	ENSG00000109072	P04004	Vitronectin	gencc
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	clinvar
SMARCAL1	HGNC:11102	ENSG00000138375	Q9NZC9	SNF2 related chromatin remodeling annealing helicase 1	clinvar
THBD	HGNC:11784	ENSG00000178726	P07204	Thrombomodulin	clinvar
TRPC6	HGNC:12338	ENSG00000137672	Q9Y210	Short transient receptor potential channel 6	clinvar
C2	HGNC:1248	ENSG00000166278	P06681	Complement C2	clinvar
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	clinvar
C3	HGNC:1318	ENSG00000125730	P01024	Complement C3	clinvar
ADAMTS13	HGNC:1366	ENSG00000160323	Q76LX8	A disintegrin and metalloproteinase with thrombospondin motifs 13	clinvar
NLRP3	HGNC:16400	ENSG00000162711	Q96P20	NACHT, LRR and PYD domains-containing protein 3	clinvar
CFHR4	HGNC:16979	ENSG00000134365	Q92496	Complement factor H-related protein 4	clinvar
CFHR3	HGNC:16980	ENSG00000116785	Q02985	Complement factor H-related protein 3	clinvar
NPHP4	HGNC:19104	ENSG00000131697	O75161	Nephrocystin-4	clinvar
COL4A3	HGNC:2204	ENSG00000169031	Q01955	Collagen alpha-3(IV) chain	clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	clinvar
COL4A5	HGNC:2207	ENSG00000188153	P29400	Collagen alpha-5(IV) chain	clinvar
C1GALT1C1	HGNC:24338	ENSG00000171155	Q96EU7	C1GALT1-specific chaperone 1	clinvar
MMACHC	HGNC:24525	ENSG00000132763	Q9Y4U1	Cyanocobalamin reductase / alkylcobalamin dealkylase	clinvar
CFHR5	HGNC:24668	ENSG00000134389	Q9BXR6	Complement factor H-related protein 5	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
DGKE	HGNC:2852	ENSG00000153933	P52429	Diacylglycerol kinase epsilon	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
MFF-DT	HGNC:41067	ENSG00000236432		MFF divergent transcript	clinvar
NPHP3-ACAD11	HGNC:48351	ENSG00000274810		NPHP3-ACAD11 readthrough (NMD candidate)	clinvar
CFH	HGNC:4883	ENSG00000000971	P08603	Complement factor H	clinvar
CFHR2	HGNC:4890	ENSG00000080910	P36980	Complement factor H-related protein 2	clinvar
LAMB2	HGNC:6487	ENSG00000172037	P55268	Laminin subunit beta-2	clinvar
CD46	HGNC:6953	ENSG00000117335	P15529	Membrane cofactor protein	clinvar
MYH9	HGNC:7579	ENSG00000100345	P35579	Myosin-9	clinvar
NPHS1	HGNC:7908	ENSG00000161270	O60500	Nephrin	clinvar
PLA2R1	HGNC:9042	ENSG00000153246	Q13018	Secretory phospholipase A2 receptor	clinvar
PLG	HGNC:9071	ENSG00000122194	P00747	Plasminogen	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFI	Complement factor I	Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways.
VTN	Vitronectin	Vitronectin is a cell adhesion and spreading factor found in serum and tissues.
CFB	Complement factor B	Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
SMARCAL1	SNF2 related chromatin remodeling annealing helicase 1	ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA.
THBD	Thrombomodulin	Endothelial cell receptor that plays a critical role in regulating several physiological processes including hemostasis, coagulation, fibrinolysis, inflammation, and angiogenesis.
TRPC6	Short transient receptor potential channel 6	Forms a receptor-activated non-selective calcium permeant cation channel.
C2	Complement C2	Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive i…
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
C3	Complement C3	Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adapt…
ADAMTS13	A disintegrin and metalloproteinase with thrombospondin motifs 13	Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.
NLRP3	NACHT, LRR and PYD domains-containing protein 3	Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis.
CFHR4	Complement factor H-related protein 4	Involved in complement regulation.
CFHR3	Complement factor H-related protein 3	Might be involved in complement regulation.
NPHP4	Nephrocystin-4	Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module.
COL4A3	Collagen alpha-3(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A5	Collagen alpha-5(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
C1GALT1C1	C1GALT1-specific chaperone 1	Probable chaperone required for the generation of 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins.
MMACHC	Cyanocobalamin reductase / alkylcobalamin dealkylase	Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate.
CFHR5	Complement factor H-related protein 5	Involved in complement regulation.
TMEM67	Meckelin	Required for ciliary structure and function.
DGKE	Diacylglycerol kinase epsilon	Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
CFH	Complement factor H	Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation.
CFHR2	Complement factor H-related protein 2	Involved in complement regulation.
LAMB2	Laminin subunit beta-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
CD46	Membrane cofactor protein	Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue.
MYH9	Myosin-9	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
NPHS1	Nephrin	Seems to play a role in the development or function of the kidney glomerular filtration barrier.
PLA2R1	Secretory phospholipase A2 receptor	Receptor for secretory phospholipase A2 (sPLA2).
PLG	Plasminogen	Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation.

Protein-family classification

Druggable: 17 · Difficult: 2 · Unknown: 14 · Druggable fraction: 0.52

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
Complement	7	56.9×	3e-10
Protease	5	5.5×	0.008
Ion channel	1	3.4×	0.772
Antibody/Immunoglobulin	1	0.9×	0.986
Kinase	1	0.8×	0.986
Other/Unknown	14	0.8×	0.986
Enzyme (other)	2	0.7×	0.986
Scaffold/PPI	1	0.5×	0.986
Transcription factor	1	0.2×	0.986

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFI	Protease	yes	3.4.21.45	SRCR, Trypsin_dom, Peptidase_S1A
VTN	Other/Unknown	no		Hemopexin-like_dom, Somatomedin_B_dom, Hemopexin_CS
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
SMARCAL1	Other/Unknown	no		SNF2_N, Helicase_C-like, HARP_dom
THBD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, C-type_lectin-like
TRPC6	Ion channel	yes		Ankyrin_rpt, TRPC_channel, TRPC6_channel
C2	Protease	yes		Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
C3	Complement	yes	3.4.21.47	Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2
ADAMTS13	Protease	yes	3.4.24.87	TSP1_rpt, Peptidase_M12B, ADAM_Cys-rich
NLRP3	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase
CFHR4	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFHR3	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
NPHP4	Other/Unknown	no		NPHP4, Ig_NPHP4_4th, Ig_NPHP4_3rd
COL4A3	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A5	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
C1GALT1C1	Enzyme (other)	yes	2.4.1.122	C1GALT1/C1GALT1_chp1
MMACHC	Enzyme (other)	yes	2.5.1.151	MMACHC
CFHR5	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
DGKE	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, PKC_DAG/PE
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
MFF-DT	Other/Unknown	no
NPHP3-ACAD11	Other/Unknown	no
CFH	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFHR2	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
LAMB2	Other/Unknown	no		EGF, LE_dom, Laminin_N
CD46	Complement	yes		Sushi_SCR_CCP_dom, CD46, Sushi/SCR/CCP_sf
MYH9	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
NPHS1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
PLA2R1	Other/Unknown	no		FN_type2_dom, Ricin_B_lectin, C-type_lectin-like
PLG	Protease	yes	3.4.21.7	Kringle, Trypsin_dom, Peptidase_S1A

Expression context

Cohort genes with no expression data: 0.

31 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)	1
broad (>20)	32
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of liver	12
liver	10
male germ line stem cell (sensu Vertebrata) in testis	6
calcaneal tendon	4
parietal pleura	3
stromal cell of endometrium	3
right uterine tube	3
buccal mucosa cell	3
germinal epithelium of ovary	2
primordial germ cell in gonad	2
vena cava	2
lower esophagus muscularis layer	2
palpebral conjunctiva	2
right lobe of thyroid gland	2
pigmented layer of retina	2
ventricular zone	2
right adrenal gland	1
gall bladder	1
sural nerve	1
gingiva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFI	240	broad	marker	germinal epithelium of ovary, parietal pleura, right lobe of liver
VTN	132	broad	marker	right lobe of liver, liver, right adrenal gland
CFB	134	broad	marker	right lobe of liver, liver, gall bladder
SMARCAL1	264	ubiquitous	marker	primordial germ cell in gonad, stromal cell of endometrium, sural nerve
THBD	259	ubiquitous	marker	gingival epithelium, gingiva, vena cava
TRPC6	180	broad	marker	right lung, lower esophagus muscularis layer, lower esophagus
C2	138	ubiquitous	marker	liver, right lobe of liver, placenta
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
C3	289	ubiquitous	marker	parietal pleura, right lobe of liver, palpebral conjunctiva
ADAMTS13	132	tissue_specific	marker	right lobe of liver, liver, right hemisphere of cerebellum
NLRP3	172	broad	marker	monocyte, mononuclear cell, leukocyte
CFHR4	79	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
CFHR3	127	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
NPHP4	165	ubiquitous	marker	right uterine tube, adenohypophysis, right lobe of thyroid gland
COL4A3	233	broad	marker	skeletal muscle tissue of biceps brachii, pigmented layer of retina, retina
COL4A4	187	broad	marker	renal medulla, metanephros cortex, pigmented layer of retina
COL4A5	267	ubiquitous	marker	mucosa of stomach, ventricular zone, lower esophagus muscularis layer
C1GALT1C1	134	ubiquitous	marker	islet of Langerhans, calcaneal tendon, rectum
MMACHC	177	ubiquitous	marker	right lobe of liver, liver, hindlimb stylopod muscle
CFHR5	15	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
DGKE	250	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, buccal mucosa cell
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
MFF-DT	158		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, bone marrow cell
NPHP3-ACAD11	133	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, endometrium
CFH	267	ubiquitous	marker	urethra, calcaneal tendon, right coronary artery
CFHR2	139		marker	right lobe of liver, liver, parietal pleura
LAMB2	268	ubiquitous	marker	apex of heart, right lobe of thyroid gland, stromal cell of endometrium
CD46	295	ubiquitous	marker	palpebral conjunctiva, adrenal tissue, mucosa of paranasal sinus
MYH9	279	ubiquitous	marker	stromal cell of endometrium, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 66.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH9	5,533
WT1	3,938
NLRP3	3,797
PLG	3,441
C3	3,199
SMARCAL1	2,899
CEP290	2,778
THBD	2,746
CFB	1,997
CFH	1,844

Intra-cohort edges

A	B	Sources
ADAMTS13	C3	string_interaction
ADAMTS13	CD46	string_interaction
ADAMTS13	CFH	string_interaction
ADAMTS13	CFHR3	string_interaction
ADAMTS13	CFHR4	string_interaction
ADAMTS13	CFHR5	string_interaction
ADAMTS13	CFI	string_interaction
ADAMTS13	DGKE	string_interaction
ADAMTS13	MMACHC	string_interaction
ADAMTS13	THBD	string_interaction
C2	C3	string_interaction
C2	CFH	string_interaction
C2	CFHR3	string_interaction
C2	CFI	string_interaction
C3	CD46	intact, string_interaction
C3	CFB	intact, string_interaction
C3	CFH	biogrid_interaction, intact, string_interaction
C3	CFHR2	intact, string_interaction
C3	CFHR3	biogrid_interaction, string_interaction
C3	CFHR4	biogrid_interaction, intact, string_interaction
C3	CFHR5	string_interaction
C3	CFI	biogrid_interaction, intact, string_interaction
CD46	CFHR2	string_interaction
CD46	CFHR3	string_interaction
CD46	CFHR4	string_interaction
CD46	CFHR5	string_interaction
CD46	CFI	intact, string_interaction
CD46	DGKE	string_interaction
CD46	THBD	string_interaction
CEP290	NPHP4	string_interaction
CEP290	TMEM67	string_interaction
CFB	CFHR2	string_interaction
CFB	CFHR3	string_interaction
CFB	CFHR4	intact, string_interaction
CFB	CFHR5	string_interaction
CFB	CFI	string_interaction
CFB	DGKE	string_interaction
CFH	CFHR3	biogrid_interaction, intact
CFH	CFI	intact, string_interaction
CFH	DGKE	string_interaction
CFH	MMACHC	string_interaction
CFHR2	DGKE	string_interaction
CFHR2	MMACHC	string_interaction
CFHR3	CFI	string_interaction
CFHR3	DGKE	string_interaction
CFHR3	THBD	string_interaction
CFHR4	DGKE	string_interaction
CFHR5	DGKE	string_interaction
CFHR5	MMACHC	string_interaction
CFHR5	THBD	string_interaction

Structural data

PDB: 23 · AlphaFold-only: 8 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C3	P01024	75
CFH	P08603	51
PLG	P00747	49
WT1	P19544	28
CFB	P00751	26
NLRP3	Q96P20	24
C2	P06681	14
THBD	P07204	13
VTN	P04004	9
MYH9	P35579	8
MMACHC	Q9Y4U1	7
CD46	P15529	7
TRPC6	Q9Y210	6
ADAMTS13	Q76LX8	5
CFHR2	P36980	4
CFI	P05156	2
COL4A3	Q01955	2
COL4A4	P53420	2
COL4A5	P29400	2
PLA2R1	Q13018	2
SMARCAL1	Q9NZC9	1
TMEM67	Q5HYA8	1
NPHS1	O60500	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFHR3	Q02985	91.93
CFHR4	Q92496	87.75
C1GALT1C1	Q96EU7	87.21
DGKE	P52429	86.18
CFHR5	Q9BXR6	83.76
LAMB2	P55268	75.94
NPHP4	O75161	72.44
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 145. Enrichment computed across 33 evidence-associated genes (30 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 30 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of Complement cascade	11	85.5×	2e-17	CFI, CFB, C2, VTN, C3, CFHR4, CFHR3, CFHR5 (+3 more)
Attachment of bacteria to epithelial cells	4	66.2×	2e-05	COL4A3, COL4A4, COL4A5, LAMB2
Activation of C3 and C5	3	126.9×	4e-05	CFB, C2, C3
Laminin interactions	4	50.8×	4e-05	COL4A3, COL4A4, COL4A5, LAMB2
ECM proteoglycans	5	25.0×	4e-05	VTN, COL4A3, COL4A4, COL4A5, LAMB2
Signaling by PDGF	4	33.8×	1e-04	COL4A3, COL4A4, COL4A5, PLG
Anchoring fibril formation	3	76.1×	2e-04	COL4A3, COL4A4, COL4A5
Fibronectin matrix formation	3	57.1×	3e-04	COL4A3, COL4A4, COL4A5
Crosslinking of collagen fibrils	3	57.1×	3e-04	COL4A3, COL4A4, COL4A5
Non-integrin membrane-ECM interactions	4	20.6×	6e-04	COL4A3, COL4A4, COL4A5, LAMB2
Alternative complement activation	2	152.3×	8e-04	CFB, C3
Integrin cell surface interactions	4	17.9×	8e-04	VTN, COL4A3, COL4A4, COL4A5
Collagen chain trimerization	3	25.9×	0.002	COL4A3, COL4A4, COL4A5
NCAM1 interactions	3	24.8×	0.002	COL4A3, COL4A4, COL4A5
Assembly of collagen fibrils and other multimeric structures	3	20.0×	0.004	COL4A3, COL4A4, COL4A5
Collagen degradation	3	17.6×	0.006	COL4A3, COL4A4, COL4A5
Collagen biosynthesis and modifying enzymes	3	17.0×	0.006	COL4A3, COL4A4, COL4A5
Effects of PIP2 hydrolysis	2	30.4×	0.016	TRPC6, DGKE
Purinergic signaling in leishmaniasis infection	2	28.2×	0.017	C3, NLRP3
Anchoring of the basal body to the plasma membrane	3	11.3×	0.017	NPHP4, TMEM67, CEP290
Defects of platelet adhesion to exposed collagen	1	380.7×	0.018	ADAMTS13
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	3	8.7×	0.032	C3, LAMB2, PLG
Defective MMACHC causes MAHCC	1	190.3×	0.033	MMACHC
Diseases of metabolism	3	8.0×	0.036	ADAMTS13, C1GALT1C1, MMACHC
Regulation of clotting cascade	2	15.5×	0.042	THBD, ADAMTS13
Developmental Lineage of Pancreatic Ductal Cells	2	15.2×	0.042	VTN, LAMB2
Defective MMADHC causes MMAHCD	1	126.9×	0.042	MMACHC
Diseases associated with O-glycosylation of proteins	2	14.4×	0.044	ADAMTS13, C1GALT1C1
Diseases of hemostasis	1	95.2×	0.049	ADAMTS13
Enhanced cleavage of VWF variant by ADAMTS13	1	95.2×	0.049	ADAMTS13

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 31 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
complement activation	8	161.1×	3e-14	CFB, C2, C3, CFHR4, CFHR3, CFHR5, CFH, CFHR2
glomerular basement membrane development	4	197.7×	5e-07	WT1, COL4A3, COL4A4, NPHS1
complement activation, alternative pathway	4	127.9×	2e-06	CFB, C3, CFHR5, CFH
complement activation, classical pathway	4	70.1×	2e-05	CFI, C2, C3, CD46
negative regulation of fibrinolysis	3	135.9×	7e-05	THBD, VTN, PLG
proteolysis	7	7.7×	0.001	CFI, CFB, THBD, C2, ADAMTS13, CFH, PLG
positive regulation of apoptotic cell clearance	2	155.3×	0.003	C2, C3
obsolete cytolysis by host of symbiont cells	2	135.9×	0.003	CFHR5, CFHR2
collagen-activated tyrosine kinase receptor signaling pathway	2	83.6×	0.006	COL4A3, COL4A5
complement activation, GZMK pathway	2	83.6×	0.006	C2, C3
positive regulation of integrin-mediated signaling pathway	2	83.6×	0.006	VTN, LAMB2
platelet activation	3	25.9×	0.006	ADAMTS13, C1GALT1C1, DGKE
negative regulation of blood coagulation	2	77.7×	0.007	THBD, VTN
collagen fibril organization	3	21.7×	0.007	COL4A3, COL4A4, COL4A5
response to bacterium	3	18.8×	0.011	CFB, C2, C3
positive regulation of receptor-mediated endocytosis	2	51.8×	0.012	VTN, C3
blood coagulation	3	16.8×	0.013	THBD, ADAMTS13, PLG
integrin-mediated signaling pathway	3	15.5×	0.015	VTN, ADAMTS13, MYH9
negative regulation of protein binding	2	40.3×	0.017	CFHR5, CFHR2
myoblast fusion	2	38.8×	0.018	MYH9, NPHS1
positive regulation of ion transmembrane transporter activity	1	543.6×	0.020	TRPC6
obsolete sequestering of extracellular ligand from receptor	1	543.6×	0.020	CD46
metanephric glomerular basement membrane development	1	543.6×	0.020	LAMB2
negative regulation of metanephric glomerular mesangial cell proliferation	1	543.6×	0.020	WT1
negative regulation of arachidonate secretion	1	543.6×	0.020	PLA2R1
neuromuscular junction development	2	34.0×	0.020	COL4A5, LAMB2
endodermal cell differentiation	2	32.0×	0.020	VTN, MYH9
regulation of animal organ formation	1	271.8×	0.024	WT1
regulation of triglyceride biosynthetic process	1	271.8×	0.024	C3
regulation of complement activation, alternative pathway	1	271.8×	0.024	CFH

Therapeutics

Drugs indicated for this disease

1 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Eculizumab	Approved (phase 4)
Crovalimab	Phase 3 (in late-stage trials)
Iptacopan	Phase 3 (in late-stage trials)
Narsoplimab	Phase 3 (in late-stage trials)
Ravulizumab	Phase 3 (in late-stage trials)

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

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 5 · Undrugged: 28

Druggability breadth: 16 of 33 evidence-associated genes (48%) 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
CFB	IPTACOPAN
NLRP3	CLOMIPHENE
PLG	AMINOCAPROIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NLRP3	11	4
PLG	11	4
CFB	1	4
TRPC6	1	2
MYH9	1	2
CFI	0	0
VTN	0	0
SMARCAL1	0	0
THBD	0	0
C2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IPTACOPAN	4	CFB
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
AMINOCAPROIC ACID	4	PLG
TELAPREVIR	4	PLG
MELAGATRAN	4	PLG
BEROTRALSTAT	4	PLG
PENTAMIDINE	4	PLG
TRANEXAMIC ACID	4	PLG
CURCUMIN	3	NLRP3
JT-001	3	NLRP3
NAFAMOSTAT	3	PLG
MILVEXIAN	3	PLG
DABIGATRAN	3	PLG
GABEXATE	3	PLG
CLEMIZOLE	2	TRPC6
TRICLOCARBAN	2	NLRP3
CLIOXANIDE	2	NLRP3
DAPANSUTRILE	2	NLRP3
USNOFLAST	2	NLRP3
MOLIBRESIB	2	MYH9
EFEGATRAN	2	PLG
INZOMELID	1	NLRP3
BMS-986299	1	NLRP3
NT-0796	1	NLRP3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
NLRP3	534	Binding:527, Functional:6, ADMET:1
PLG	480	Binding:467, ADMET:7, Functional:6
CFB	33	Binding:33
TRPC6	30	Binding:30
C3	15	Binding:15
MYH9	10	Binding:10
C2	4	Binding:4
ADAMTS13	3	Binding:3
PLA2R1	3	Binding:3
VTN	1	Binding:1
DGKE	1	Binding:1
CFH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CFI	3.4.21.45	complement factor I
CFB	3.4.21.47	alternative-complement-pathway C3/C5 convertase
C3	3.4.21.47	alternative-complement-pathway C3/C5 convertase
ADAMTS13	3.4.24.87	ADAMTS13 endopeptidase
C1GALT1C1	2.4.1.122	N-acetylgalactosaminide beta-1,3-galactosyltransferase
MMACHC	2.5.1.151	alkylcobalamin dealkylase
DGKE	2.7.1.107	diacylglycerol kinase (ATP)
PLG	3.4.21.7	plasmin

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NLRP3	534
PLG	480

Pharmacogenomics

Cohort genes with a PharmGKB record: 31; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

24 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)
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
AMINOCAPROIC ACID	4	PLG
TELAPREVIR	4	PLG
MELAGATRAN	4	PLG
BEROTRALSTAT	4	PLG
PENTAMIDINE	4	PLG
TRANEXAMIC ACID	4	PLG
CURCUMIN	3	NLRP3
JT-001	3	NLRP3
NAFAMOSTAT	3	PLG
MILVEXIAN	3	PLG
DABIGATRAN	3	PLG
GABEXATE	3	PLG
CLEMIZOLE	2	TRPC6
TRICLOCARBAN	2	NLRP3
CLIOXANIDE	2	NLRP3
DAPANSUTRILE	2	NLRP3
USNOFLAST	2	NLRP3
MOLIBRESIB	2	MYH9
EFEGATRAN	2	PLG
INZOMELID	1	NLRP3
BMS-986299	1	NLRP3
NT-0796	1	NLRP3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CFB, NLRP3, PLG
B	Phased (≥1) drug, not yet approved	2	TRPC6, MYH9
C	Druggable family + PDB, no drug	9	CFI, C2, C3, ADAMTS13, MMACHC, CFH, CFHR2, CD46, NPHS1
D	Druggable family + AlphaFold only, no drug	5	CFHR4, CFHR3, C1GALT1C1, CFHR5, DGKE
E	Difficult family or no structure, no drug	14	VTN, SMARCAL1, THBD, WT1, NPHP4, COL4A3, COL4A4, COL4A5, TMEM67, CEP290 (+4 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CFI	0	CFB
C3	15	CFB
CFHR3	0	CFB
COL4A4	0	MYH9
CFHR5	0	CFB
DGKE	1	CFB
VTN	1	—
SMARCAL1	0	—
THBD	0	—
C2	4	—
WT1	0	—
ADAMTS13	3	—
CFHR4	0	—
NPHP4	0	—
COL4A3	0	—
COL4A5	0	—
C1GALT1C1	0	—
MMACHC	0	—
TMEM67	0	—
CEP290	0	—
MFF-DT	0	—
NPHP3-ACAD11	0	—
CFH	1	—
CFHR2	0	—
LAMB2	0	—
CD46	0	—
NPHS1	0	—
PLA2R1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 40.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	18
PHASE2	12
PHASE3	8
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07308574	PHASE4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT02574403	PHASE4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT04861259	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT04958265	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT05795140	PHASE3	RECRUITING	Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS
NCT05935215	PHASE3	RECRUITING	Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT02949128	PHASE3	COMPLETED	Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03131219	PHASE3	COMPLETED	Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03205995	PHASE3	TERMINATED	Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome
NCT04889430	PHASE3	COMPLETED	Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
NCT00838513	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)
NCT00844428	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive aHUS
NCT00844545	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS
NCT00844844	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
NCT01193348	PHASE2	COMPLETED	An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
NCT01194973	PHASE2	COMPLETED	An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
NCT01757431	PHASE2	COMPLETED	The Safety and Efficacy of Eculizumab in Japanese Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT02464891	PHASE2	TERMINATED	Complement Inhibition in aHUS Dialysis Patients
NCT03303313	PHASE2	WITHDRAWN	A Study of an Investigational Drug, Cemdisiran (ALN-CC5), in Patients With Atypical Hemolytic Uremic Syndrome
NCT03518203	PHASE2	COMPLETED	Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
NCT03999840	PHASE2	WITHDRAWN	Eculizumab to Cemdisiran Switch in aHUS
NCT04725812	PHASE2	TERMINATED	Complement Regulation to Undo Systemic Harm in Preeclampsia
NCT01522183	Not specified	RECRUITING	Atypical Hemolytic-Uremic Syndrome (aHUS) Registry
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05805202	Not specified	RECRUITING	Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy
NCT05996731	Not specified	RECRUITING	Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06099236	Not specified	ACTIVE_NOT_RECRUITING	A Prospective, Non-interventional, Observational Study of Presentation, Treatment Patterns and Outcomes in Atypical Hemolytic Uremic Syndrome Patients
NCT06312644	Not specified	RECRUITING	Study of Ultomiris® (Ravulizumab) Safety in Pregnancy
NCT07218536	Not specified	RECRUITING	The Burden of Atypical Hemolytic Uremic Syndrome and The Clinical Characteristics of Patients in Egyptian Hospitals A Multicenter, Observational, Retrospective Cohort Study in Egypt
NCT07399730	Not specified	NOT_YET_RECRUITING	Ravulizumab Outcomes in Polish Patients With aHUS
NCT01522170	Not specified	TERMINATED	aHUS Observational Long Term Follow-Up
NCT01755429	Not specified	COMPLETED	To Characterize the Safety and Tolerability of Eculizumab in Two Japanese aHUS Patients
NCT01770951	Not specified	COMPLETED	A Retrospective, Observational, Non-interventional Trial to Assess Eculizumab Treatment Effect in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT02614898	Not specified	TERMINATED	Evaluation of Potential Predictors of Disease Progression in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Including Genetics, Biomarkers, and Treatment
NCT02626663	Not specified	WITHDRAWN	The Role of Microparticles as a Biomarker
NCT03574506	Not specified	UNKNOWN	Eculizumab Use in the Postpartum Period for the Treatment of Pregnancy Associated aHUS: A Case Series
NCT03605511	Not specified	UNKNOWN	TTP and aHUS in Complicated Pregnancies
NCT04749810	Not specified	COMPLETED	Observational Study of Elizaria® in aHUS Patients
NCT05405777	Not specified	COMPLETED	A Retrospective Study to Evaluate the Clinical Outcome According to Treatment in aHUS Patients in South Korea

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ECULIZUMAB	4	11
RAVULIZUMAB	4	5
CROVALIMAB	4	2
IPTACOPAN	4	2
AVACOPAN	4	1
CEMDISIRAN	3	2
NARSOPLIMAB	3	1