Hemolytic uremic syndrome, atypical, susceptibility to, 1

Summary

Hemolytic uremic syndrome, atypical, susceptibility to, 1 (MONDO:0009335) is a disease caused by CFH (GenCC Strong), with 7 cohort genes. The dominant Reactome pathway is Regulation of Complement cascade (5 cohort genes).

At a glance

• Causal gene: CFH (GenCC Strong)
• Cohort genes: 7
• ClinVar variants: 366

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemolytic uremic syndrome, atypical, susceptibility to, 1
Mondo ID	MONDO:0009335
OMIM	235400
UMLS	C2749604
MedGen	412743
Is cancer (heuristic)	no

Also known as: AHUS1 · hemolytic uremic syndrome, atypical, susceptibility to · hemolytic uremic syndrome, atypical, susceptibility to, 1 · hemolytic uremic syndrome, atypical, susceptibility to, type 1

Data availability: 366 ClinVar variants · 5 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease susceptibility › inherited disease susceptibility › hemolytic uremic syndrome, atypical, susceptibility to, 1

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

Subtypes (2): atypical hemolytic-uremic syndrome with H factor anomaly, atypical hemolytic-uremic syndrome with anti-factor H antibodies

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

366 retrieved; paginated sample, class counts are floors:

189 uncertain significance, 58 conflicting classifications of pathogenicity, 37 benign/likely benign, 20 likely pathogenic, 19 likely benign, 15 pathogenic, 14 benign, 5 pathogenic/likely pathogenic, 4 pathogenic, low penetrance, 2 not provided, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 risk factor, 1 likely pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068249	NM_000186.4(CFH):c.157C>T (p.Arg53Cys)	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
1454075	NM_000186.4(CFH):c.2602dup (p.Ile868fs)	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
16553	NM_000186.4(CFH):c.2697T>A (p.Tyr899Ter)	CFH	Pathogenic	criteria provided, single submitter
16559	NM_000186.4(CFH):c.3514G>T (p.Glu1172Ter)	CFH	Pathogenic	criteria provided, single submitter
16563	NM_000186.4(CFH):c.3592G>T (p.Glu1198Ter)	CFH	Pathogenic, low penetrance	criteria provided, single submitter
2025535	NM_000186.4(CFH):c.2575C>T (p.Gln859Ter)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21089	NC_000001.10:g.(196712876_196712928)_(196797494_196797546)del	CFH	Pathogenic	no assertion criteria provided
294526	NM_000186.4(CFH):c.3643C>T (p.Arg1215Ter)	CFH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3234076	NM_000186.4(CFH):c.245-1G>C	CFH	Pathogenic	criteria provided, single submitter
3236385	NM_000186.4(CFH):c.1609del (p.His537fs)	CFH	Pathogenic	criteria provided, single submitter
3383230	NM_000186.4(CFH):c.2485dup (p.Tyr829fs)	CFH	Pathogenic	criteria provided, single submitter
429034	NM_000186.4(CFH):c.2397del (p.Glu800fs)	CFH	Pathogenic	no assertion criteria provided
438685	NM_000186.4(CFH):c.710_711del (p.Lys236_Cys237insTer)	CFH	Pathogenic	no assertion criteria provided
4849208	NM_000186.4(CFH):c.3007G>T (p.Glu1003Ter)	CFH	Pathogenic	criteria provided, single submitter
599109	NM_000186.4(CFH):c.1318_1327del (p.Pro440fs)	CFH	Pathogenic	no assertion criteria provided
635491	NM_000186.4(CFH):c.1126C>T (p.Gln376Ter)	CFH	Pathogenic, low penetrance	criteria provided, single submitter
829824	NM_000186.4(CFH):c.3134-2A>G	CFH	Pathogenic, low penetrance	criteria provided, single submitter
829949	NM_000186.4(CFH):c.2535dup (p.Gln846fs)	CFH	Pathogenic	no assertion criteria provided
4293094	NM_021023.6(CFHR3):c.613+3_613+6del	CFHR3	Pathogenic	criteria provided, single submitter
812509	NM_003647.3(DGKE):c.447del (p.Lys150fs)	DGKE	Pathogenic	criteria provided, single submitter
222958	NM_004054.4(C3AR1):c.355_356dup (p.Asp119fs)	C3AR1	Likely pathogenic	no assertion criteria provided
1936765	NM_000186.4(CFH):c.2236+1G>C	CFH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2429376	NM_000186.4(CFH):c.3173_3182del (p.Ala1057_Tyr1058insTer)	CFH	Likely pathogenic	criteria provided, single submitter
2507420	NM_000186.4(CFH):c.2975T>G (p.Leu992Ter)	CFH	Likely pathogenic	criteria provided, single submitter
3066309	NM_000186.4(CFH):c.1520-2A>G	CFH	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 15 · 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
CFH	Strong	Autosomal dominant	hemolytic uremic syndrome, atypical, susceptibility to, 1	9
CFHR1	Limited	Autosomal dominant	hemolytic uremic syndrome, atypical, susceptibility to, 1	4
CFHR3	Limited	Unknown	hemolytic uremic syndrome, atypical, susceptibility to, 1

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFHR3	Orphanet:329931	C3 glomerulonephritis
CFH	Orphanet:200421	Immunodeficiency with factor H anomaly
CFH	Orphanet:244242	HELLP syndrome
CFH	Orphanet:244275	De novo thrombotic microangiopathy after kidney transplantation
CFH	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
CFH	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
CFH	Orphanet:75376	Familial drusen
CFH	Orphanet:93571	Dense deposit disease
CFHR1	Orphanet:329931	C3 glomerulonephritis
CFHR1	Orphanet:93571	Dense deposit disease
C3	Orphanet:280133	Complement component 3 deficiency
C3	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
DGKE	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
DGKE	Orphanet:357008	Hemolytic uremic syndrome with DGKE deficiency
BAAT	Orphanet:238475	Familial hypercholanemia

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFHR3	HGNC:16980	ENSG00000116785	Q02985	Complement factor H-related protein 3	gencc,clinvar
CFH	HGNC:4883	ENSG00000000971	P08603	Complement factor H	gencc,clinvar
CFHR1	HGNC:4888	ENSG00000244414	Q03591	Complement factor H-related protein 1	gencc,clinvar
C3	HGNC:1318	ENSG00000125730	P01024	Complement C3	clinvar
C3AR1	HGNC:1319	ENSG00000171860	Q16581	C3a anaphylatoxin chemotactic receptor	clinvar
DGKE	HGNC:2852	ENSG00000153933	P52429	Diacylglycerol kinase epsilon	clinvar
BAAT	HGNC:932	ENSG00000136881	Q14032	Bile acid-CoA:amino acid N-acyltransferase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFHR3	Complement factor H-related protein 3	Might be involved in complement regulation.
CFH	Complement factor H	Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation.
CFHR1	Complement factor H-related protein 1	Involved in complement regulation.
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…
C3AR1	C3a anaphylatoxin chemotactic receptor	Receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a, stimulating chemotaxis, granule enzyme release and superoxide anion production.
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.
BAAT	Bile acid-CoA:amino acid N-acyltransferase	Catalyzes the amidation of bile acids (BAs) with the amino acids taurine and glycine.

Protein-family classification

Druggable: 7 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	4	153.1×	2e-08
Kinase	1	4.0×	0.344
GPCR	1	3.4×	0.344
Enzyme (other)	1	1.7×	0.456

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFHR3	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFH	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFHR1	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
C3	Complement	yes	3.4.21.47	Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2
C3AR1	GPCR	yes		GPCR_Rhodpsn, Formyl_rcpt-rel, Anaphtx_C3AR1
DGKE	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, PKC_DAG/PE
BAAT	Enzyme (other)	yes	2.3.1.65	Thio_Ohase/aa_AcTrfase, BAAT_C, Acyl-CoA_thioEstase_long-chain

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of liver	4
liver	3
male germ line stem cell (sensu Vertebrata) in testis	2
calcaneal tendon	1
right coronary artery	1
urethra	1
palpebral conjunctiva	1
parietal pleura	1
leukocyte	1
monocyte	1
mononuclear cell	1
Brodmann (1909) area 23	1
buccal mucosa cell	1
middle temporal gyrus	1
gall bladder	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFHR3	127	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
CFH	267	ubiquitous	marker	urethra, calcaneal tendon, right coronary artery
CFHR1	125		marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
C3	289	ubiquitous	marker	parietal pleura, right lobe of liver, palpebral conjunctiva
C3AR1	262	broad	marker	monocyte, mononuclear cell, leukocyte
DGKE	250	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, buccal mucosa cell
BAAT	105	tissue_specific	marker	liver, right lobe of liver, gall bladder

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C3	3,199
C3AR1	2,278
CFH	1,844
DGKE	1,045
BAAT	964
CFHR1	599
CFHR3	373

Intra-cohort edges

A	B	Sources
C3	C3AR1	string_interaction
C3	CFH	biogrid_interaction, intact, string_interaction
C3	CFHR1	string_interaction
C3	CFHR3	biogrid_interaction, string_interaction
C3AR1	CFH	string_interaction
CFH	CFHR1	intact
CFH	CFHR3	biogrid_interaction, intact
CFH	DGKE	string_interaction
CFHR1	DGKE	string_interaction
CFHR3	DGKE	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C3	P01024	75
CFH	P08603	51
C3AR1	Q16581	18
CFHR1	Q03591	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BAAT	Q14032	95.31
CFHR3	Q02985	91.93
DGKE	P52429	86.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. Enrichment computed across 7 evidence-associated genes (7 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 7 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	5	166.5×	8e-10	CFHR3, CFH, CFHR1, C3, C3AR1
Purinergic signaling in leishmaniasis infection	2	120.8×	0.002	C3, C3AR1
Alternative complement activation	1	326.3×	0.030	C3
Peptide ligand-binding receptors	2	21.2×	0.030	C3, C3AR1
Activation of C3 and C5	1	181.3×	0.034	C3
Cell recruitment (pro-inflammatory response)	1	163.1×	0.034	C3AR1
Complement cascade	1	90.6×	0.042	C3AR1
Recycling of bile acids and salts	1	85.9×	0.042	BAAT
Bile acid and bile salt metabolism	1	70.9×	0.042	BAAT
Effects of PIP2 hydrolysis	1	65.3×	0.042	DGKE
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	1	65.3×	0.042	BAAT
G alpha (i) signalling events	2	11.1×	0.042	C3, C3AR1
Synthesis of bile acids and bile salts	1	58.3×	0.043	BAAT
Protein localization	1	27.2×	0.077	BAAT
Peroxisomal protein import	1	24.7×	0.077	BAAT
Leishmania infection	1	23.3×	0.077	C3AR1
Parasitic Infection Pathways	1	23.3×	0.077	C3AR1
Neutrophil degranulation	2	6.6×	0.077	C3, C3AR1
Metabolism of steroids	1	19.7×	0.086	BAAT
Post-translational protein phosphorylation	1	14.3×	0.112	C3
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	12.4×	0.117	C3
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	12.4×	0.117	C3
Class A/1 (Rhodopsin-like receptors)	1	10.6×	0.130	C3AR1
GPCR ligand binding	1	9.2×	0.143	C3AR1
GPCR downstream signalling	1	6.2×	0.199	C3AR1
Signaling by GPCR	1	5.7×	0.206	C3AR1
Metabolism of lipids	1	4.5×	0.247	BAAT
Innate Immune System	1	3.6×	0.285	C3AR1
Infectious disease	1	3.5×	0.285	C3AR1
Disease	1	1.9×	0.458	C3AR1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 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	4	356.7×	1e-08	CFHR3, CFH, CFHR1, C3
complement receptor mediated signaling pathway	2	321.0×	4e-04	C3, C3AR1
complement activation, alternative pathway	2	283.2×	4e-04	CFH, C3
positive regulation of vascular endothelial growth factor production	2	141.6×	0.001	C3, C3AR1
bile acid conjugation	1	2407.4×	0.005	BAAT
regulation of triglyceride biosynthetic process	1	1203.7×	0.005	C3
regulation of complement activation, alternative pathway	1	1203.7×	0.005	CFH
complement-dependent cytotoxicity	1	1203.7×	0.005	C3
positive regulation of type IIa hypersensitivity	1	802.5×	0.005	C3
positive regulation of activation of membrane attack complex	1	802.5×	0.005	C3
oviduct epithelium development	1	802.5×	0.005	C3
vertebrate eye-specific patterning	1	802.5×	0.005	C3
fatty acid metabolic process	2	55.3×	0.005	C3, BAAT
phospholipase C-activating G protein-coupled receptor signaling pathway	2	37.6×	0.005	C3AR1, DGKE
inflammatory response	3	16.2×	0.005	CFH, C3, C3AR1
positive regulation of angiogenesis	2	33.0×	0.006	C3, C3AR1
complement-mediated synapse pruning	1	601.9×	0.006	C3
regulation of complement-dependent cytotoxicity	1	481.5×	0.007	CFH
glycine metabolic process	1	401.2×	0.008	BAAT
taurine metabolic process	1	401.2×	0.008	BAAT
positive regulation of apoptotic cell clearance	1	343.9×	0.008	C3
positive regulation of D-glucose transmembrane transport	1	300.9×	0.008	C3
regulation of complement activation	1	300.9×	0.008	CFH
glycerolipid metabolic process	1	300.9×	0.008	DGKE
obsolete cytolysis by host of symbiont cells	1	300.9×	0.008	CFHR1
lipid phosphorylation	1	240.7×	0.010	DGKE
positive regulation of lipid storage	1	200.6×	0.011	C3
positive regulation of phagocytosis, engulfment	1	185.2×	0.011	C3
complement activation, GZMK pathway	1	185.2×	0.011	C3
neuron remodeling	1	172.0×	0.011	C3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
C3AR1	LOPERAMIDE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C3AR1	1	4
CFHR3	0	0
CFH	0	0
CFHR1	0	0
C3	0	0
DGKE	0	0
BAAT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LOPERAMIDE HYDROCHLORIDE	4	C3AR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
C3AR1	75	Functional:45, Binding:28, ADMET:2
C3	15	Binding:15
CFH	1	Binding:1
DGKE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
C3	3.4.21.47	alternative-complement-pathway C3/C5 convertase
DGKE	2.7.1.107	diacylglycerol kinase (ATP)
BAAT	2.3.1.65	bile acid-CoA:amino acid N-acyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
LOPERAMIDE HYDROCHLORIDE	4	C3AR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	C3AR1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	CFH, CFHR1, C3
D	Druggable family + AlphaFold only, no drug	3	CFHR3, DGKE, BAAT
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CFHR3	0	—
CFH	1	—
CFHR1	0	—
C3	15	—
DGKE	1	—
BAAT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.