BRCA2

Tumour Suppressor
Breast cancer type 2 susceptibility protein UniProt accession P51587

Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis.

Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures.

May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability.

Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180)

Source: UniProt

Monomer and dimer (PubMed:20729858). Interacts with RAD51; regulates RAD51 recruitment and function at sites of DNA repair (PubMed:12442171, PubMed:15800615, PubMed:18317453, PubMed:20729832, PubMed:20729859). Interacts with WDR16, USP11, DMC1, ROCK2 and NPM1 (PubMed:15314155, PubMed:15967112, PubMed:20729832, PubMed:21084279).

Interacts with SEM1; the interaction masks a nuclear export signal in BRCA2 (PubMed:10373512, PubMed:16205630, PubMed:21719596, PubMed:24013206). Interacts with both nonubiquitinated and monoubiquitinated FANCD2; this complex also includes XRCC3 and phosphorylated FANCG (PubMed:15115758, PubMed:15199141, PubMed:18212739). Part of a BRCA complex containing BRCA1, BRCA2 and PALB2 (PubMed:19369211).

Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Within the complex, interacts with ERCC5/XPG and PALB2 (PubMed:26833090). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (PubMed:16793542, PubMed:19369211, PubMed:19609323, PubMed:24141787, PubMed:26833090, PubMed:28319063).

Interacts with BRCA1 only in the presence of PALB2 which serves as the bridging protein (PubMed:19369211). Interacts with POLH; the interaction is direct (PubMed:24485656). Interacts with the TREX-2 complex subunits PCID2 and SEM1 (PubMed:21719596, PubMed:24896180).

Interacts with HSF2BP and BRME1; the interaction with HSF2BP is direct and allows the formation of a ternary complex (PubMed:31242413). The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (By similarity)

Source: UniProt
Nucleus, Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Source: UniProt

Highest levels of expression in breast and thymus, with slightly lower levels in lung, ovary and spleen

Source: UniProt
  • Breast cancer (BC)

    A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type.

    Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.

  • Pancreatic cancer 2 (PNCA2)

    A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.

  • Breast-ovarian cancer, familial, 2 (BROVCA2)

    A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.

  • Fanconi anemia complementation group D1 (FANCD1)

    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.

  • Glioma 3 (GLM3)

    Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.

  • Medulloblastoma (MDB)

    Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.

Source: UniProt

Click a pathway to open the interactive Reactome viewer.

Pathway list and interactive viewer: Reactome

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to BRCA2, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 256

NCT ID Condition Brief Title Phase Status
NCT01608074 BRCA1 Mutation, BRCA2 Mutation, Hereditary Breast and Ovarian Cancer Radical Fimbriectomy for Young BRCA Mutation Carriers NA ACTIVE_NOT_RECRUITING
NCT03685331 Metastatic Breast Cancer, Locally Advanced Breast Cancer, Advanced Breast Cancer, BRCA2 Mutation, BRCA1 Mutation HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer PHASE1 COMPLETED
NCT06177171 BRCA1 Mutation, BRCA2 Mutation, BRCA Mutation, PALB2 Gene Mutation, Checkpoint Kinase 2 Gene Mutation, ATM Gene Mutation Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors PHASE1 RECRUITING
NCT02760849 Deleterious BARD1 Gene Mutation, Deleterious BRCA1 Gene Mutation, Deleterious BRCA2 Gene Mutation, Deleterious BRIP1 Gene Mutation, Deleterious EPCAM Gene Mutation, Deleterious MLH1 Gene Mutation, Deleterious MSH2 Gene Mutation, Deleterious MSH6 Gene Mutation, Deleterious PALB2 Gene Mutation, Deleterious PMS2 Gene Mutation, Deleterious RAD51C Gene Mutation, Deleterious RAD51D Gene Mutation, Hereditary Breast and Ovarian Cancer Syndrome, Premenopausal Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations NA ACTIVE_NOT_RECRUITING
NCT04718675 Relapsed Solid Tumors, Refractory Solid Tumors, Non-Hodgkin Lymphoma, HGSOC, Platinum Resistant High Grade Serous Ovarian Cancer A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC) PHASE1, PHASE2 TERMINATED
NCT03351803 BRCA1 Mutation, BRCA2 Mutation BRCA Founder OutReach (BFOR) Study N/A ACTIVE_NOT_RECRUITING
NCT02451735 Breast Cancer Genetic Counseling for Breast Cancer Survivors (GC for BC) NA COMPLETED
NCT03544983 BRCA1 Mutation, BRCA2 Mutation Genetic Education in BRCA Families NA ENROLLING_BY_INVITATION
NCT04038502 Metastatic Castrate Resistant Prostate Cancer, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L Mutations Carboplatin or Olaparib for BRcA Deficient Prostate Cancer PHASE2 RECRUITING
NCT04584255 Stage I Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, Breast Cancer, HER2-negative Breast Cancer, Germline BRCA1 Gene Mutation, Germline BRCA2 Gene Mutation, Deleterious PALB2 Gene Mutation Niraparib + Dostarlimab In BRCA Mutated Breast Cancer PHASE2 ACTIVE_NOT_RECRUITING