CFB

Chr 6ADDigenic dominantAR

complement factor B

Also known as: AHUS4, ARMD14, BF, BFD, CFAB, CFBD, FB, FBI12

This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Hemolytic uremic syndrome, atypical, susceptibility to, 4}MIM #612924
AD
{Macular degeneration, age-related, 14, reduced risk of}MIM #615489
Digenic dominant
Complement factor B deficiencyMIM #615561
AR
441
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
5
Active trials
Clinical SummaryCFB
🧬
Gene-Disease Validity (ClinGen)
atypical hemolytic-uremic syndrome with B factor anomaly · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 222 VUS of 441 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.52LOEUF
pLI 0.000
Z-score 3.99
OE 0.33 (0.220.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.48Z-score
OE missense 0.79 (0.720.87)
326 obs / 410.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.220.52)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.720.87)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
01.21.6
LoF obs/exp: 14 / 41.9Missense obs/exp: 326 / 410.4Syn Z: 0.73

ClinVar Variant Classifications

441 submitted variants in ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic7
VUS222
Likely Benign177
Benign6
Conflicting17
12
Pathogenic
7
Likely Pathogenic
222
VUS
177
Likely Benign
6
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
6
6
0
12
Likely Pathogenic
2
4
1
0
7
VUS
11
178
28
5
222
Likely Benign
0
10
77
90
177
Benign
0
0
4
2
6
Conflicting
17
Total1319811697441

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CFB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

COMPLEMENT FACTOR B; CFB
MIM #138470 · *

{Hemolytic uremic syndrome, atypical, susceptibility to, 4}

MIM #612924

Molecular basis of disorder known

Autosomal dominant

{Macular degeneration, age-related, 14, reduced risk of}

MIM #615489

Molecular basis of disorder known

Digenic dominant

Complement factor B deficiency

MIM #615561

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CFB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy in age-related macular degeneration.
Kaarniranta K et al.·Autophagy
2023Review
Influenza-associated thrombotic microangiopathies.
Bitzan M et al.·Pediatr Nephrol
2018Review
Top 10 resultsSearch PubMed ↗