FANCB

Chr XXLR

FA complementation group B

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

NCBI Gene: 2187ENSG00000181544UniProt: Q8NB91

This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group BMIM #300514
XLR
Fanconi anemia, complementation group BMIM #300514
XLR
UniProtFanconi anemia complementation group B
424
ClinVar variants
21
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— FANCB
🧬
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.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 216 VUS of 424 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.23LOEUF
pLI 0.996
Z-score 4.04
OE 0.05 (0.02–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
-0.04Z-score
OE missense 1.01 (0.92–1.11)
294 obs / 292.0 exp
Tolerant

Tolerant to missense variation

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.0.05 (0.02–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 1 / 20.9Missense obs/exp: 294 / 292.0Syn Z: 0.43

ClinVar Variant Classifications

424 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic4
VUS216
Likely Benign171
Benign12
Conflicting4
17
Pathogenic
4
Likely Pathogenic
216
VUS
171
Likely Benign
12
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
14
0
17
Likely Pathogenic
3
0
1
0
4
VUS
1
203
10
2
216
Likely Benign
0
18
49
104
171
Benign
0
1
4
7
12
Conflicting
—4
Total722278113424

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.

Gene2Phenotype Curations

FANCB-related Fanconi anemia

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Fanconi anemia, complementation group B

MIM #300514

Molecular basis of disorder known

X-linked recessive
FANCB GENE; FANCB
MIM #300515 · *

Fanconi anemia, complementation group B

MIM #300514

Molecular basis of disorder known

X-linked recessive
📖
GeneReview available — FANCB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathogenic mutations identified by a multimodality approach in 117 Japanese Fanconi anemia patients.
Mori M et al.·Haematologica
2019Clinical trial
Whole exome sequencing analysis of 167 men with primary infertility.
Zhou H et al.·BMC Med Genomics
2024
Association of clinical severity with FANCB variant type in Fanconi anemia.
Jung M et al.·Blood
2020
Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia.
Malcher A et al.·Andrology
2022
Fanconi anemia and DNA repair.
Grompe M et al.·Hum Mol Genet
2001Review
Genotype-phenotype associations in Fanconi anemia: A literature review.
Fiesco-Roa MO et al.·Blood Rev
2019Review
Genetic inactivation of FAAP100 causes Fanconi anemia due to disruption of the monoubiquitin ligase core complex.
Kuehl J et al.·J Clin Invest
2025
Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype.
Asur RS et al.·Mol Genet Genomic Med
2018Case report
Analysis of FANCB and FANCN/PALB2 fanconi anemia genes in BRCA1/2-negative Spanish breast cancer families.
García MJ et al.·Breast Cancer Res Treat
2009
[Analysis of a fetus with multiple malformations due to a hemizygous variant of FANCB gene].
Gao L et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

External Resources

Links to major genomics databases and tools