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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]
BRCA2 mutations in the germline have become a hallmark for hereditary breast and ovarian cancers. Variants that have been demonstrated to reduce the function of the protein have been shown to increase the risk for these cancers, as well as prostate and pancreatic cancer. These findings have been the impetus for the increased popularity of genetic testing of healthy individuals to assess risk. Recent studies in ovarian cancer have also demonstrated that BRCA mutation status can predict treatment response. A number of trials assessing BRCA mutation status have shown an improved response to platinum agents, and more recently has led to the FDA-approval of PARP inhibitors for BRCA-positive ovarian cancers. These studies have resulted in the Society of Gynecologic Oncology to recommend germline BRCA testing in all patients with a diagnosis of ovarian cancer.
BRCA2 (BRCA2 DNA Repair Associated) is a Protein Coding gene. Diseases associated with BRCA2 include Fanconi Anemia, Complementation Group D1 and Breast Cancer. Among its related pathways are Homologous DNA Pairing and Strand Exchange and Meiosis. Gene Ontology (GO) annotations related to this gene include protease binding and histone acetyltransferase activity.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH13J032314 | Promoter/Enhancer | 2.2 | EPDnew Ensembl ENCODE CraniofacialAtlas | 612.8 | +0.7 | 678 | 2.9 | HNRNPL CREB1 TEAD4 ZNF629 TFE3 IKZF1 ZNF692 POLR2A BACH1 JUND | BRCA2 KY212394 ZAR1L N4BP2L2 N4BP2L1 | |
GH13J032334 | Enhancer | 0.4 | Ensembl | 13.8 | +19.7 | 19715 | 1.6 | RFX1 FOXA2 ZNF146 | BRCA2 KY212394 ZAR1L RF00994-269 N4BP2L1 | |
GH13J032375 | Enhancer | 0.2 | Ensembl | 10.1 | +61.3 | 61315 | 2 | N4BP2L1 ATP8A2P2 IFIT1P1 BRCA2 RF00994-269 ZAR1L | ||
GH13J032045 | Enhancer | 1.2 | FANTOM5 ENCODE dbSUPER | 1.2 | -268.5 | -268476 | 1.6 | GATAD2A TFE3 SOX13 RCOR2 JUND RBFOX2 RXRB SOX6 TOE1 CEBPA | FRY-AS1 N4BP2L2 FRY N4BP2L1 BRCA2 lnc-RXFP2-2 lnc-RXFP2-3 | |
GH13J032115 | Enhancer | 0.7 | FANTOM5 ENCODE | 1.6 | -199.4 | -199411 | 2.4 | RUNX3 SPI1 REST POLR2A MYC MAX | N4BP2L2 BRCA2 N4BP2L1 piR-48209-157 lnc-ZAR1L-4 FRY |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002020 | protease binding | IPI | 15314155 |
GO:0003677 | DNA binding | IEA | -- |
GO:0003697 | single-stranded DNA binding | IDA | 20729832 |
GO:0004402 | NOT histone acetyltransferase activity | IDA | 9824164 |
GO:0005515 | protein binding | IPI | 9560268 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000784 | nuclear chromosome, telomeric region | IDA | 21076401 |
GO:0000800 | lateral element | IDA | 9774970 |
GO:0005634 | nucleus | IBA,IDA | 9560268 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Resolution of D-loop Structures through Holliday Junction Intermediates | ||
2 | DNA Double-Strand Break Repair |
.53
|
|
3 | Homologous DNA Pairing and Strand Exchange | ||
4 | BRCA1 Pathway |
Fanconi's Anaemia Pathway
.01
|
BRCA1 Pathway
-
|
5 | Meiosis |
.73
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000722 | telomere maintenance via recombination | IEA | -- |
GO:0000724 | double-strand break repair via homologous recombination | IBA,IMP | 21719596 |
GO:0001556 | oocyte maturation | IEA | -- |
GO:0001833 | inner cell mass cell proliferation | IEA | -- |
GO:0006281 | DNA repair | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Rucaparib | Approved, Investigational | Pharma | inhibitor, Biomarker, other | PARP inhibitor, PARP Inhibitors, Other | 57 | |
Olaparib | Approved | Pharma | inhibitor, Biomarker, other | PARP inhibitor, PARP Inhibitors, Other, Poly(ADPRIBOSE) polymerase (PARP) inhibitors | 277 | |
Vitamin C | Approved | Nutra | 748,748 | |||
Niraparib | Approved, Investigational | Pharma | inhibitor, Biomarker | PARP inhibitor, PARP Inhibitors | 93 | |
Cisplatin | Approved | Pharma | Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum | 3412 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | BRCA2 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | BRCA2 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | BRCA2 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Brca2 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Brca2 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Oppossum (Monodelphis domestica) |
Mammalia | BRCA2 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | BRCA2 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | BRCA2 31 |
|
OneToOne | |
Zebrafish (Danio rerio) |
Actinopterygii | brca2 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 13 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
188253 | Uncertain Significance: Hereditary breast and ovarian cancer syndrome; not provided | 32,338,162(+) | TG/CA | ||
231569 | Uncertain Significance: Hereditary breast and ovarian cancer syndrome; Hereditary cancer-predisposing syndrome | 32,379,775(+) | ATCA/TGAT | ||
236899 | Conflicting Interpretations: Hereditary breast and ovarian cancer syndrome; Hereditary cancer-predisposing syndrome | 32,355,094(+) | CA/TG | ||
267655 | Pathogenic: Breast-ovarian cancer, familial 2 | 32,317,677(+) | GTCAGAAAAGTCTTTT | ||
267707 | Pathogenic: Breast-ovarian cancer, familial 2 | 32,378,939(+) | ACCTACAACACAGAAA |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3306840 | CNV | mobile element insertion | 20981092 |
esv3329650 | CNV | insertion | 20981092 |
esv3426269 | CNV | insertion | 20981092 |
esv3580597 | CNV | loss | 25503493 |
nsv1127324 | CNV | deletion | 24896259 |
nsv1145657 | CNV | deletion | 24896259 |
nsv475474 | CNV | novel sequence insertion | 20440878 |
nsv819799 | CNV | gain | 19587683 |
nsv832576 | CNV | gain | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
fanconi anemia, complementation group d1 |
|
|
breast cancer |
|
|
breast-ovarian cancer, familial 2 |
|
|
pancreatic cancer 2 |
|
|
glioma susceptibility 3 |
|