Complement factor b deficiency

Summary

Complement factor b deficiency (MONDO:0014255) is a disease with pathogenic variants reported in CFB (ClinVar). This page aggregates 1 associated gene.

At a glance

• Genes with pathogenic ClinVar variants: CFB
• Cohort genes: 1
• ClinVar variants: 21
• Phenotypes (HPO): 6

Clinical features

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (curated from Orphanet + OMIM; top 6 shown, Orphanet frequencies first):

HPO ID	Term	Frequency
HP:0001287	Meningitis	—
HP:0002090	Pneumonia	—
HP:0002586	Peritonitis	—
HP:0002718	Recurrent bacterial infections	—
HP:0005381	Recurrent Neisseria meningitidis infection	—
HP:0005416	Decreased circulating complement factor B concentration	—

Identifiers

Disease identifiers

Field	Value
Canonical name	complement factor b deficiency
Mondo ID	MONDO:0014255
OMIM	615561
UMLS	C3809950
MedGen	816280
Is cancer (heuristic)	no

Also known as: CFBD · complement factor b deficiency

Data availability: 21 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › complement factor b deficiency

Sibling subtypes (1,895): inherited bleeding disorder, platelet-type, infantile liver failure, febrile seizures, familial, hereditary hypophosphatemic rickets, hypothyroidism, congenital, nongoitrous, isolated microphthalmia, anemia, hypochromic microcytic with iron overload, Chiari malformation, developmental dysplasia of the hip, bone marrow failure syndrome, Zimmermann-Laband syndrome, autoimmune disease, multisystem, infantile-onset, multinodular goiter, orofacial cleft, spondylocostal dysostosis, X-linked disease, Y-linked disease, cornea plana, epithelial-stromal TGFBI dystrophy, congenital diarrhea, … (+1,875 more under hereditary disease)

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

21 retrieved; paginated sample, class counts are floors:

7 benign/likely benign, 7 uncertain significance, 2 pathogenic, 2 conflicting classifications of pathogenicity, 1 benign, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3906267	CFB, 1-BP DUP, NT1938	CFB	Pathogenic	no assertion criteria provided
3906268	CFB, GLY396ARG	CFB	Pathogenic	no assertion criteria provided
3066149	NM_001710.6(CFB):c.898-2A>C	CFB	Likely pathogenic	criteria provided, single submitter
829990	NM_001710.6(CFB):c.1374G>A (p.Met458Ile)	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
92246	NM_001710.6(CFB):c.766C>T (p.Gln256Ter)	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
356267	NM_001710.6(CFB):c.-3G>A	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1940636	NM_001710.6(CFB):c.97C>G (p.Pro33Ala)	CFB	Uncertain significance	criteria provided, multiple submitters, no conflicts
92247	NM_001710.6(CFB):c.1895_1898del (p.Phe632fs)	CFB	Uncertain significance	criteria provided, single submitter
1959340	NM_001710.6(CFB):c.1603C>T (p.His535Tyr)	CFB	Uncertain significance	criteria provided, single submitter
2439926	NM_001710.6(CFB):c.124del (p.Gly41_Val42insTer)	CFB	Uncertain significance	criteria provided, single submitter
973630	NM_001710.6(CFB):c.1198A>G (p.Thr400Ala)	CFB	Uncertain significance	no assertion criteria provided
16076	NM_001710.5(CFB):c.94C>T (p.Arg32Trp)	CFB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
16077	NM_001710.6(CFB):c.26T>A (p.Leu9His)	CFB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
225313	NM_001710.6(CFB):c.1598A>G (p.Lys533Arg)	CFB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
225314	NM_001710.6(CFB):c.1697A>C (p.Glu566Ala)	CFB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
356272	NM_001710.6(CFB):c.450A>G (p.Arg150=)	CFB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
356284	NM_001710.6(CFB):c.1137C>T (p.Arg379=)	CFB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
356295	NM_001710.6(CFB):c.2100C>T (p.Gly700=)	CFB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1209734	NM_001710.6(CFB):c.2140-74A>G	CFB	Benign	criteria provided, multiple submitters, no conflicts
1575611	NM_001710.6(CFB):c.1778+8C>T	CFB	Likely benign	criteria provided, multiple submitters, no conflicts

Pathogenic / likely-pathogenic variants link to their full per-variant reference — ACMG evidence, calibrated predictors, gnomAD frequency — on Sugi Variant.

Genes & proteins

Molecular basis

The molecular function of this disease’s causal gene(s), from UniProt. Attributed to the gene/protein — reporting UniProt’s curation, not an assertion about this disease’s clinical phenotype.

CFB — Complement factor B (P00751) · ClinVar-linked · Belongs to the peptidase S1 family. Function: 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 adaptive immune system. Localization / cofactor: Secreted Cell surface UniProt gene–disease: Macular degeneration, age-related, 14 (ARMD14) [MIM:615489] A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as …

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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.

1 cohort genes:

Gene	Classification	Inheritance	Disease	Records
CFB	Strong	Autosomal dominant	atypical hemolytic-uremic syndrome with B factor anomaly	5

Orphanet rare-disease linkage (cohort genes)

1 cohort genes:

Gene	Orphanet ID	Rare disease
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes

1 cohort genes:

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

Cohort function summary

Lead sentence per gene, UniProt-curated.

1 cohort genes:

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…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort has 1 family-classified gene — counts only (too few for over-representation statistics).

Family	Genes
Protease	1

Per-gene assignment

1 cohort genes:

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

3 tissues:

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

Per-gene tissue summary

1 cohort genes:

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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFB	1,573

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures

1 cohort genes:

Symbol	UniProt	PDB entries
CFB	P00751	28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Cohort has 1 gene with Reactome annotation — too few for over-representation statistics, so the pathways below are membership (what the cohort gene participates in), not enrichment.

Pathways by enrichment

Cohort has 1 annotated gene — membership only (too few for over-representation statistics).

7 pathways:

Pathway	Genes	Sample cohort genes
Alternative complement activation	1	CFB
Activation of C3 and C5	1	CFB
Complement cascade	1	CFB
Initial triggering of complement	1	CFB
Regulation of Complement cascade	1	CFB
Innate Immune System	1	CFB
Immune System	1	CFB

GO biological processes by enrichment

Cohort has 1 annotated gene — membership only (too few for over-representation statistics).

3 GO terms:

GO term	Genes	Sample cohort genes
complement activation, alternative pathway	1	CFB
response to bacterium	1	CFB
proteolysis	1	CFB

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 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

Drugs targeting cohort genes

1 drugs:

Molecule	Max phase	Targets in cohort
Iptacopan	4	CFB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity

1 cohort genes by assay count:

Symbol	Assays	Type breakdown
CFB	33	Binding:33

Cohort enzymes (BRENDA EC)

1 cohort enzymes:

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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.

1 compounds:

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.