BRCA2

HIGH

BRCA2 DNA repair associated

Chromosome: 13q13.1

Gene Overview

BRCA2 encodes a tumor suppressor that binds RAD51 and promotes its loading onto single-stranded DNA during homologous recombination. Like BRCA1, germline loss-of-function mutations confer high risk of breast and ovarian cancer; BRCA2 mutations also increase prostate and pancreatic cancer risk. BRCA2 facilitates strand invasion and Holliday junction formation; deficiency causes chromosomal aberrations and sensitivity to crosslinking agents. The gene is cell-cycle regulated and expressed in proliferating tissues. Male BRCA2 carriers have elevated breast cancer risk. Functional domains include the BRC repeats (RAD51 binding) and the DNA-binding domain. PARP inhibitors show efficacy in BRCA2-mutant cancers.

Molecular Function

  • homologous recombination
  • RAD51 loading
  • DNA strand exchange
  • replication fork stabilization

Protein class: tumor suppressor

Regulatory Annotation

Promoter activity: E2F and cell-cycle regulation; p53 response elements.

Enhancer associations: Breast cancer risk variants in regulatory regions.

eQTL tissues: breast, ovary, prostate

Tissue Expression Context

breastTPM range: 2-8GTEx vv8
testisTPM range: 5-20GTEx vv8

Pathways

Linked Diseases & Exposures

Diseases

Exposures

Mechanistic Hypotheses

BRCA2 deficiency prevents RAD51 nucleofilament formation; unrepaired DNA breaks accumulate, enabling malignant transformation; PARP inhibition causes synthetic lethality.

BRCA2-RAD51 interaction well characterized; PARPi approved for BRCA2-mutant cancers.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

  1. 1.Wooster R, et al. (1994). Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. doi:10.1126/science.8196475
  2. 2.GTEx Consortium (2020). GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. doi:10.1126/science.aaz1776
  3. 3.Moynahan ME, Jasin M (2010). BRCA2 and homologous recombination in ovarian cancer development. Cancer Research. doi:10.1158/0008-5472.CAN-10-0789