BRCA2 BRCA2 DNA repair associated [Homo sapiens (human)] - Gene

Summary

Official Symbol: BRCA2provided by HGNC
Official Full Name: BRCA2 DNA repair associatedprovided by HGNC
Primary source: HGNC:HGNC:1101
See related: Ensembl:ENSG00000139618 MIM:600185; AllianceGenome:HGNC:1101
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FAD; FACD; FAD1; GLM3; BRCC2; FANCD; PNCA2; FANCD1; XRCC11; BROVCA2
Summary: Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]
Expression: Broad expression in bone marrow (RPKM 2.9), testis (RPKM 2.2) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 13q13.1

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (32315508..32400268)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (31532753..31617510)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (32889645..32974405)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.
Title: Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.
Deleterious and ethnic-related BRCA1/2 mutations in tissue and blood of Egyptian colorectal cancer patients and its correlation with human papillomavirus.
Title: Deleterious and ethnic-related BRCA1/2 mutations in tissue and blood of Egyptian colorectal cancer patients and its correlation with human papillomavirus.
Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation.
Title: Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation.
CRISPR/Cas9-mediated knock-in of BRCA1/2 mutations restores response to olaparib in pancreatic cancer cell lines.
Title: CRISPR/Cas9-mediated knock-in of BRCA1/2 mutations restores response to olaparib in pancreatic cancer cell lines.
Functional analysis and clinical classification of 462 germline BRCA2 missense variants affecting the DNA binding domain.
Title: Functional analysis and clinical classification of 462 germline BRCA2 missense variants affecting the DNA binding domain.
BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer.
Title: BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer.
Central nervous system metastases in breast cancer patients with germline BRCA pathogenic variants compared to non-carriers: a matched-pair analysis.
Title: Central nervous system metastases in breast cancer patients with germline BRCA pathogenic variants compared to non-carriers: a matched-pair analysis.
Prevalence and spectrum of germline BRCA1 and BRCA2 in a cohort of ovarian cancer patients from the Salento peninsula (Southern Italy): a matter of preventive health.
Title: Prevalence and spectrum of germline BRCA1 and BRCA2 in a cohort of ovarian cancer patients from the Salento peninsula (Southern Italy): a matter of preventive health.
Functional annotation of variants of the BRCA2 gene via locally haploid human pluripotent stem cells.
Title: Functional annotation of variants of the BRCA2 gene via locally haploid human pluripotent stem cells.
Reclassifying BRCA1 c.4358-2A > G and BRCA2 c.475 + 5G > C variants from "Uncertain Significance" to "Pathogenic" based on minigene assays and clinical evidence.
Title: Reclassifying BRCA1 c.4358-2A > G and BRCA2 c.475 + 5G > C variants from "Uncertain Significance" to "Pathogenic" based on minigene assays and clinical evidence.

Submit: New GeneRIF Correction See all GeneRIFs (1617)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in BRCA2 that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Breast-ovarian cancer, familial, susceptibility to, 2 MedGen: C2675520 OMIM: 612555 GeneReviews: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer	Compare labs
Familial cancer of breast MedGen: C0346153 OMIM: 114480 GeneReviews: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer	Compare labs
Fanconi anemia complementation group D1 MedGen: C1838457 OMIM: 605724 GeneReviews: Wilms Tumor Predisposition, Fanconi Anemia	Compare labs
Glioma susceptibility 3 MedGen: C2751641 OMIM: 613029 GeneReviews: Not available	Compare labs
Hereditary breast ovarian cancer syndrome MedGen: C0677776 GeneReviews: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer	Compare labs
Malignant tumor of prostate MedGen: C0376358 OMIM: 176807 GeneReviews: Not available	Compare labs
Medulloblastoma MedGen: C0025149 OMIM: 155255 GeneReviews: Not available	Compare labs
Pancreatic cancer, susceptibility to, 2 MedGen: C3150546 OMIM: 613347 GeneReviews: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer	Compare labs
Wilms tumor 1 MedGen: CN033288 OMIM: 194070 GeneReviews: Wilms Tumor Predisposition, PAX6-Related Aniridia, WT1 Disorder	Compare labs

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-07-14) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2021-07-14) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies identify four ER negative-specific breast cancer risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genotyping identifies 41 new loci associated with breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC13918P2 (e-PCR)
- UniSTS:270878

PMC13918P3 (e-PCR)
- UniSTS:270879

PMC13918P4 (e-PCR)
- UniSTS:270880

PMC13918P5 (e-PCR)
- UniSTS:270881

PMC13918P6 (e-PCR)
- UniSTS:270882

D13S1788 (e-PCR)
- UniSTS:474668

STS-X95157 (e-PCR)
- UniSTS:27960

REN34178 (e-PCR)
- UniSTS:358978

PMC23830P1 (e-PCR)
- UniSTS:272209

G48219 (e-PCR)
- UniSTS:95316

STS-X95152 (e-PCR)
- UniSTS:50804

PMC310899P14 (e-PCR)
- UniSTS:272803

RH68440 (e-PCR)
- UniSTS:34471

BRCA2 (e-PCR)
- UniSTS:505289

SHGC-81356 (e-PCR)
- UniSTS:103159

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables gamma-tubulin binding	IPI Inferred from Physical Interaction more info	PubMed
enables histone H3 acetyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone H4 acetyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
NOT enables histone acetyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator	IEA Inferred from Electronic Annotation more info
involved_in brain development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to ionizing radiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular senescence	IEA Inferred from Electronic Annotation more info
involved_in centrosome duplication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via homologous recombination	IBA Inferred from Biological aspect of Ancestor more info
involved_in double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
involved_in double-strand break repair via homologous recombination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of protein localization to telomere	IDA Inferred from Direct Assay more info	PubMed
involved_in female gonad development	IEA Inferred from Electronic Annotation more info
involved_in hematopoietic stem cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in inner cell mass cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IEA Inferred from Electronic Annotation more info
involved_in male meiosis I	IEA Inferred from Electronic Annotation more info
involved_in mitotic recombination-dependent replication fork processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of mammary gland epithelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleotide-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in oocyte maturation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA damage checkpoint	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of cytokinesis	IEA Inferred from Electronic Annotation more info
involved_in response to UV-C	IEA Inferred from Electronic Annotation more info
involved_in response to X-ray	IEA Inferred from Electronic Annotation more info
involved_in response to gamma radiation	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info
involved_in telomere maintenance via recombination	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of BRCA2-MAGE-D1 complex	IDA Inferred from Direct Assay more info	PubMed
part_of DNA repair complex	IPI Inferred from Physical Interaction more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in lateral element	IDA Inferred from Direct Assay more info	PubMed
part_of nuclear ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in secretory granule	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: breast cancer type 2 susceptibility protein

Names: BRCA1/BRCA2-containing complex, subunit 2; BRCA2 DNA repair associated protein; DNA repair-associated BRCA2; Fanconi anemia group D1 protein; breast and ovarian cancer susceptibility gene, early onset; breast and ovarian cancer susceptibility protein 2; breast cancer 2 tumor suppressor; breast cancer 2, early onset; mutant BRCA2; mutant DNA repair-associated protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012772.3 RefSeqGene

Range

5001..89193

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_293

mRNA and Protein(s)

NM_000059.4 → NP_000050.3 breast cancer type 2 susceptibility protein isoform 1

Status: REVIEWED

Source sequence(s)

AL137247, AL445212

Consensus CDS

CCDS9344.1

UniProtKB/Swiss-Prot

O00183, O15008, P51587, Q13879, Q5TBJ7

UniProtKB/TrEMBL

A0A386IN23, A0A7P0T9D7

Related

ENSP00000369497.3, ENST00000380152.8

Conserved Domains (5) summary

cd04494
Location:2804 → 3054

BRCA2DBD_OB2; A subfamily of OB folds corresponding to the second OB fold (OB2) of the 800-amino acid C-terminal ssDNA binding domain (DBD) of BRCA2 (breast cancer susceptibility gene 2) protein, called BRCA2DBD. BRCA2 participates in homologous recombination-mediated ...

pfam00634
Location:1213 → 1243

BRCA2; BRCA2 repeat

pfam09103
Location:2670 → 2793

BRCA-2_OB1; BRCA2, oligonucleotide/oligosaccharide-binding, domain 1

pfam09104
Location:3054 → 3186

BRCA-2_OB3; BRCA2, oligonucleotide/oligosaccharide-binding, domain 3

pfam09169
Location:2481 → 2667

BRCA-2_helical; BRCA2, helical
NM_001406719.1 → NP_001393648.1 breast cancer type 2 susceptibility protein isoform 3

Status: REVIEWED

Source sequence(s)

AL137247, AL445212
NM_001406720.1 → NP_001393649.1 breast cancer type 2 susceptibility protein isoform 2

Status: REVIEWED

Source sequence(s)

AL137247, AL445212

UniProtKB/TrEMBL

A0A8V8TPZ2

Related

ENSP00000514856.2, ENST00000700202.2
NM_001406721.1 → NP_001393650.1 breast cancer type 2 susceptibility protein isoform 4

Status: REVIEWED

Source sequence(s)

AL137247, AL445212
NM_001406722.1 → NP_001393651.1 breast cancer type 2 susceptibility protein isoform 5

Status: REVIEWED

Source sequence(s)

AL137247, AL445212