atypical hemolytic-uremic syndrome with B factor anomaly

Summary

atypical hemolytic-uremic syndrome with B factor anomaly (MONDO:0013042) is a disease caused by CFB (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CFB (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 66

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atypical hemolytic-uremic syndrome with B factor anomaly
Mondo ID	MONDO:0013042
OMIM	612924
Orphanet	93578
UMLS	C2752038
MedGen	416691
GARD	0018554
Is cancer (heuristic)	no

Also known as: aHUS with B factor anomaly · AHUS4 · aHUS4 · atypical HUS with B factor anomaly · D-HUS with B factor anomaly · hemolytic uremic syndrome, atypical, susceptibility to, 4 · hemolytic uremic syndrome, atypical, susceptibility to, type 4 · hemolytic-uremic syndrome without diarrhea with B factor anomaly · hemolytic-uremic syndrome without diarrhoea with B factor anomaly

Data availability: 66 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › atypical hemolytic-uremic syndrome › atypical hemolytic uremic syndrome with complement gene abnormality › atypical hemolytic-uremic syndrome with B factor anomaly

Related subtypes (4): atypical hemolytic-uremic syndrome with MCP/CD46 anomaly, atypical hemolytic-uremic syndrome with I factor anomaly, atypical hemolytic-uremic syndrome with C3 anomaly, atypical hemolytic-uremic syndrome with thrombomodulin anomaly

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

66 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 21 benign/likely benign, 18 conflicting classifications of pathogenicity, 3 benign, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16080	NM_001710.6(CFB):c.967A>G (p.Lys323Glu)	CFB	Pathogenic	criteria provided, single submitter
16079	NM_001710.6(CFB):c.858C>G (p.Phe286Leu)	CFB	Likely pathogenic	criteria provided, single submitter
908037	NM_000063.6(C2):c.1577A>G (p.Lys526Arg)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1575611	NM_001710.6(CFB):c.1778+8C>T	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356268	NM_001710.6(CFB):c.221G>A (p.Arg74His)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356269	NM_001710.6(CFB):c.291G>A (p.Glu97=)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356270	NM_001710.6(CFB):c.321C>T (p.His107=)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356275	NM_001710.6(CFB):c.604C>T (p.Arg202Trp)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356278	NM_001710.6(CFB):c.720G>A (p.Glu240=)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356279	NM_001710.6(CFB):c.724A>C (p.Ile242Leu)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356283	NM_001710.6(CFB):c.1037-10C>T	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356288	NM_001710.6(CFB):c.1407C>G (p.Ile469Met)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356291	NM_001710.6(CFB):c.1593T>C (p.Asp531=)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356298	NM_001710.6(CFB):c.*47C>T	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903818	NM_001710.6(CFB):c.1290C>T (p.Val430=)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903888	NM_001710.6(CFB):c.1956+10G>A	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906097	NM_001710.6(CFB):c.274A>T (p.Thr92Ser)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906166	NM_001710.6(CFB):c.784G>A (p.Val262Ile)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
907233	NM_001710.6(CFB):c.1838C>T (p.Thr613Ile)	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992561	NM_001710.6(CFB):c.658+7T>C	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1048765	NM_001710.6(CFB):c.503C>T (p.Pro168Leu)	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1959340	NM_001710.6(CFB):c.1603C>T (p.His535Tyr)	CFB	Uncertain significance	criteria provided, single submitter
2136371	NM_001710.6(CFB):c.608G>A (p.Arg203Gln)	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
2671634	NM_001710.6(CFB):c.2023G>A (p.Val675Met)	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3236135	NM_001710.6(CFB):c.713T>G (p.Leu238Arg)	CFB	Uncertain significance	criteria provided, single submitter
356267	NM_001710.6(CFB):c.-3G>A	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
356276	NM_001710.6(CFB):c.656A>T (p.Gln219Leu)	CFB	Uncertain significance	criteria provided, single submitter
356286	NM_001710.6(CFB):c.1227A>G (p.Leu409=)	CFB	Uncertain significance	criteria provided, single submitter
356289	NM_001710.6(CFB):c.1524C>A (p.His508Gln)	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
356294	NM_001710.6(CFB):c.1889C>T (p.Ala630Val)	CFB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
CFB	Strong	Autosomal dominant	atypical hemolytic-uremic syndrome with B factor anomaly	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
C2	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	gencc,clinvar
C2	HGNC:1248	ENSG00000166278	P06681	Complement C2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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…
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…

Protein-family classification

Druggable: 2 · 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
Protease	2	36.6×	7e-04

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
C2	Protease	yes		Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	2
right lobe of liver	2
gall bladder	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFB	134	broad	marker	right lobe of liver, liver, gall bladder
C2	138	ubiquitous	marker	liver, right lobe of liver, placenta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFB	1,997
C2	937

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFB	P00751	26
C2	P06681	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of C3 and C5	2	1268.9×	2e-06	CFB, C2
Regulation of Complement cascade	2	233.1×	4e-05	CFB, C2
Alternative complement activation	1	1142.0×	0.001	CFB
Initial triggering of complement	1	300.5×	0.003	C2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	2	624.1×	2e-05	CFB, C2
response to bacterium	2	193.7×	1e-04	CFB, C2
positive regulation of apoptotic cell clearance	1	1203.7×	0.002	C2
response to thyroid hormone	1	1053.2×	0.002	C2
proteolysis	2	34.2×	0.002	CFB, C2
complement activation, GZMK pathway	1	648.1×	0.003	C2
complement activation, alternative pathway	1	495.6×	0.003	CFB
complement activation, classical pathway	1	271.8×	0.005	C2
response to nutrient	1	147.8×	0.008	C2
response to lipopolysaccharide	1	62.4×	0.016	C2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFB	1	4
C2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IPTACOPAN	4	CFB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CFB	33	Binding:33
C2	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CFB	3.4.21.47	alternative-complement-pathway C3/C5 convertase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
IPTACOPAN	4	CFB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CFB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	C2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
C2	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.