BRCA2

BRCA2 (Breast cancer type 2 susceptibility protein) is a critical tumor suppressor that functions as a mediator of homologous recombination (HR) DNA repair. The protein contains multiple functional domains: BRC repeats that bind RAD51 recombinase, a DNA-binding domain (DBD) with OB folds and tower domain that binds ssDNA, and a C-terminal recombinase-binding region (CTRB) that engages both DNA and RAD51. BRCA2 loads and stabilizes RAD51 onto RPA-coated single-stranded DNA to form the presynaptic filament required for strand invasion during HR. Additionally, BRCA2 protects stalled and reversed replication forks from MRE11-mediated nucleolytic degradation, a function genetically separable from but coordinated with HR. Key partners include RAD51, PALB2, BRCA1-BARD1, and DSS1. Loss of BRCA2 function causes homologous recombination deficiency (HRD), conferring sensitivity to PARP inhibitors and platinum agents. Biallelic mutations cause Fanconi anemia (complementation group D1/FANCD1). BRCA2 localizes predominantly to the nucleus at DNA damage sites.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• dna_repair_synthetic_lethality via Fallopian Tube Cancer, Ovarian High-Grade Serous Carcinoma named in the module itself
• rtk_grb2_signaling_adaptation named in the module itself