GeneBe

FANCB

protein-coding

FA complementation group B, the group of FA complementation groups|FA core complex

Gene summary

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]

MANE transcript

NM_001018113.3

Inheritance

AR, XLR, XL

ClinVar variants

P:31U:414B:278

Top phenotype

Fanconi anemia,complementation group B

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chrX:14,690,388-14,873,255

External References & Databases

Ensembl (ENSG00000181544)NCBI Gene (2187)OMIM (300515)HGNC:3583GenCCUniProt (Q8NB91)AlphaFoldClinVar (FANCB)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~182.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

VACTERL with hydrocephalusSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010172

Submitter: Orphanet

Fanconi anemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019391

Submitter: Orphanet

Fanconi anemia complementation group BDEFINITIVE

Inheritance Pattern: XLR

Disease ID:MONDO:0010351

Submitter: Natera

VACTERL association, X-linked, with or without hydrocephalusSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010752

Submitter: Genomics England PanelApp

Fanconi anemia complementation group BDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010351

Submitter: G2P

Fanconi anemia complementation group BDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010351

Submitter: ClinGen

FANCB was first reported concerning Fanconi anemia complementation group B, with X-linked inheritance (OMIM:300514), in 2004 (Meetei et al., PMID: 15502827). Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and a high frequency of chromosomal aberrations pointing to a defect in DNA repair. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in the molecular mechanism and inheritance pattern and phenotypic variability. Therefore, the following disease entities have been lumped, with Fanconi Anemia B, VACTERL association, X-linked, with or without hydrocephalus; VACTERLX (OMIM: 314390), VACTERL association with hydrocephalus (OMIM: 276950). Twelve variants (5 missense,1 in-frame indel, 1 nonsense, and 4 frameshift) have been reported in 12 probands in 3 publications (PMIDs: 15502827, 21910217, 23613520,) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be loss of function (LOF). This gene-disease association is also supported by animal models and in vitro functional assays (5 points. PMIDs: 26123487, 26658157, 32106311). The Fancb-/Y male mice resemble the human phenotype of patients with pathogenic variants in FANCB related to Fanconi Anemia, such as hypogonadism, testicular failure and reduced fertility. The cells of the hematopoietic system of Fancb−/Y mice are hypersensitive to DNA cross-linking agent mitomycin C (MMC). In summary, FANCB is definitively associated with Fanconi anemia complementation group B, X-linked inheritance (HP:0001417) recessive (HP:0001419). This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.

Fanconi anemia complementation group BSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010351

Submitter: Labcorp Genetics (formerly Invitae)

Fanconi anemia complementation group BSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010351

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Fanconi anemia,complementation group BXL

Manifestation: Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal

Intervention: Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic

Rationale: Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management

Refs: 15502827; 16679491; 20301575; 21910217; 22052692Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FANCB variants in ClinVar

14 Conditions Cataloged
Fanconi anemiaTotal: 610
Fanconi anemia complementation group BTotal: 146
not providedTotal: 94
Inborn genetic diseasesTotal: 70
not specifiedTotal: 67
VACTERL association, X-linked, with or without hydrocephalusTotal: 54
FANCB-related disorderTotal: 50
History of neurodevelopmental disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001018113.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
16
clinvar
175
clinvar
16
clinvar
 207
missense
2
clinvar
1
clinvar
377
clinvar
81
clinvar
6
clinvar
 467
nonsense
4
clinvar
2
clinvar
7
clinvar
 13
start loss
0
frameshift
14
clinvar
3
clinvar
2
clinvar
 19
splice donor/acceptor (+/-2bp)
2
clinvar
3
clinvar
12
clinvar
 17
Total22941425622723

Highest pathogenic variant AF is 0.0000027300698

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001018113.3RefSeqNP_001018123.18MANE Select
ENST00000650831.1EnsemblENSP00000498215.18MANE Select
NM_001324162.2RefSeqNP_001311091.18Standard
NM_001410764.1RefSeqNP_001397693.111Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Fanconi anemia pathway - Homo sapiens (human)
  • Fanconi Anemia Pathway
  • DNA Repair
  • Fanconi anemia pathway

Biological Process

  • interstrand cross-link repair
  • positive regulation of double-strand break repair via homologous recombination
  • replication-born double-strand break repair via sister chromatid exchange
  • negative regulation of double-strand break repair via homologous recombination

Molecular Function

  • protein binding

Cellular Component

  • nucleoplasm
  • Fanconi anaemia nuclear complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000398334
Coding exons
8
Length
29663
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.04172942921.010.00002055676
Missense (PolyPhen)4462.4520.704551433
Synonymous0.4271011070.9470.000007671596
Loss of Function4.04120.90.04780.00000137475

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: DNA repair protein required for FANCD2 ubiquitination. {ECO:0000269|PubMed:15502827}.;
Disease
DISEASE: Fanconi anemia complementation group B (FANCB) [MIM:300514]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Some severe FANCB cases manifest features of VACTERL syndrome with hydrocephalus. {ECO:0000269|PubMed:16679491}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.317

Intolerance Scores

RVIS EVS
-0.4
RVIS percentile EVS
26.85

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.811

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.