FANCB

Chr XXLR

FA complementation group B

Also known as: FA2, FAAP90, FAAP95, FAB, FACB

This gene encodes a DNA repair protein required for FANCD2 ubiquitination and is assembled into a nucleoprotein complex that repairs DNA lesions. Mutations cause Fanconi anemia complementation group B and can also cause VACTERL syndrome with hydrocephalus. The gene follows X-linked recessive inheritance and is highly constrained against loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.232 OMIM phenotypes
Clinical SummaryFANCB
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Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group B · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 177 VUS of 400 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — FANCB
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.996
Z-score 4.04
OE 0.05 (0.020.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
-0.04Z-score
OE missense 1.01 (0.921.11)
294 obs / 292.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.05 (0.020.23)
00.351.4
Missense OE1.01 (0.921.11)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 1 / 20.9Missense obs/exp: 294 / 292.0Syn Z: 0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFANCB-related Fanconi anemiaLOFXLR
DN
0.3296th %ile
GOF
0.2298th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 26% of P/LP variants are LoF · LOEUF 0.23

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic6
VUS177
Likely Benign159
Benign24
Conflicting13
21
Pathogenic
6
Likely Pathogenic
177
VUS
159
Likely Benign
24
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
17
0
21
Likely Pathogenic
4
2
0
0
6
VUS
3
161
10
3
177
Likely Benign
0
14
46
99
159
Benign
0
0
13
11
24
Conflicting
13
Total1017886113400

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

View in ClinVar →

Protein Context — Lollipop Plot

FANCB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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