BRCA2 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human BRCA2 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene BRCA2, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene BRCA2, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene BRCA2 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene BRCA2 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene BRCA2, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene BRCA2, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene BRCA2, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene BRCA2 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene BRCA2, summarize transcription factor regulatory data. If BRCA2 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate BRCA2 — names with evidence type (ChIP-seq / predicted / experimentally validated) If BRCA2 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene BRCA2 protein as a drug target, summarize pharmacology data. If BRCA2 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If BRCA2 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene BRCA2, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene BRCA2, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in BRCA2: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
BRCA2 (breast cancer type 2 susceptibility protein; HGNC:1101, chromosome 13q12.3) is one of the most clinically significant tumor suppressor genes in human genetics, encoding a 3,418-residue nuclear protein essential for homologous recombination repair of DNA double-strand breaks. Pathogenic germline variants — of which ClinVar catalogues ~1,800 pathogenic and ~200 likely pathogenic entries out of ~21,181 total — confer autosomal dominant susceptibility to breast, ovarian, pancreatic, and prostate cancers, while biallelic loss causes Fanconi anemia complementation group D1. BRCA2 is not itself a drug target, but BRCA2-deficient tumors are selectively killed by PARP inhibitors (including olaparib, rucaparib, talazoparib, niraparib, veliparib, and fluzoparib) through synthetic lethality. The protein’s interaction network is centered on RAD51-mediated strand exchange and the Fanconi anemia pathway, with top interactors including PALB2, FANCD2, BRCA1, and RAD51. Expression is highest in germ cells (score 94.3 in male germ line stem cells) and broadly ubiquitous, consistent with a universal role in genome maintenance.
BRCA2 — Reference
Cross-database identifier and functional mapping reference for BRCA2.
Gene identifiers
BRCA2 DNA repair associated
- HGNC ID: HGNC:1101
- Approved symbol: BRCA2
- Ensembl gene ID: ENSG00000139618
- NCBI Entrez Gene ID: 675
- OMIM gene ID: 600185
- Genomic location (GRCh38):
- Chromosome: 13
- Start position: 32,315,086
- End position: 32,400,268
- Strand: +
Transcript identifiers
Ensembl transcripts (19 total)
| ENST ID | Biotype |
|---|---|
| ENST00000380152 | protein_coding |
| ENST00000470094 | nonsense_mediated_decay |
| ENST00000528762 | nonsense_mediated_decay |
| ENST00000530893 | protein_coding |
| ENST00000533776 | retained_intron |
| ENST00000544455 | protein_coding |
| ENST00000614259 | nonsense_mediated_decay |
| ENST00000665585 | nonsense_mediated_decay |
| ENST00000666593 | nonsense_mediated_decay |
| ENST00000680887 | protein_coding |
| ENST00000700199 | retained_intron |
| ENST00000700200 | retained_intron |
| ENST00000700201 | nonsense_mediated_decay |
| ENST00000700202 | protein_coding |
| ENST00000700203 | retained_intron |
| ENST00000713677 | nonsense_mediated_decay |
| ENST00000713678 | protein_coding |
| ENST00000713679 | nonsense_mediated_decay |
| ENST00000713680 | protein_coding |
RefSeq transcripts (9 NM_ mRNA accessions)
| Accession | MANE Select |
|---|---|
| NM_000059 | ✓ |
| NM_001081001 | |
| NM_001110394 | |
| NM_001180104 | |
| NM_001406719 | |
| NM_001406720 | |
| NM_001406721 | |
| NM_001406722 | |
| NM_001432077 |
CCDS identifier
CCDS9344
Canonical/MANE Select transcript: ENST00000380152 — 27 exons
| Exon # | ENSE ID | Start | End | Coordinates (chr13:+) |
|---|---|---|---|---|
| 1 | ENSE00004011581 | 32315508 | 32315667 | 32315508–32315667 |
| 2 | ENSE00001484009 | 32316422 | 32316527 | 32316422–32316527 |
| 3 | ENSE00003666217 | 32319077 | 32319325 | 32319077–32319325 |
| 4 | ENSE00003659301 | 32325076 | 32325184 | 32325076–32325184 |
| 5 | ENSE00003739878 | 32326101 | 32326150 | 32326101–32326150 |
| 6 | ENSE00003747332 | 32326242 | 32326282 | 32326242–32326282 |
| 7 | ENSE00003749714 | 32326499 | 32326613 | 32326499–32326613 |
| 8 | ENSE00003731761 | 32330919 | 32331030 | 32330919–32331030 |
| 9 | ENSE00003714754 | 32329443 | 32329492 | 32329443–32329492 |
| 10 | ENSE00000939167 | 32332272 | 32333387 | 32332272–32333387 |
| 11 | ENSE00000939168 | 32336265 | 32341196 | 32336265–32341196 |
| 12 | ENSE00000939169 | 32344558 | 32344653 | 32344558–32344653 |
| 13 | ENSE00000939171 | 32346827 | 32346896 | 32346827–32346896 |
| 14 | ENSE00000939173 | 32354861 | 32355288 | 32354861–32355288 |
| 15 | ENSE00000939174 | 32356428 | 32356609 | 32356428–32356609 |
| 16 | ENSE00000939175 | 32357742 | 32357929 | 32357742–32357929 |
| 17 | ENSE00001394102 | 32362523 | 32362693 | 32362523–32362693 |
| 18 | ENSE00000939177 | 32363179 | 32363533 | 32363179–32363533 |
| 19 | ENSE00003461148 | 32376670 | 32376791 | 32376670–32376791 |
| 20 | ENSE00000939178 | 32370402 | 32370557 | 32370402–32370557 |
| 21 | ENSE00000939180 | 32370956 | 32371100 | 32370956–32371100 |
| 22 | ENSE00000939183 | 32379317 | 32379515 | 32379317–32379515 |
| 23 | ENSE00000939185 | 32379750 | 32379913 | 32379750–32379913 |
| 24 | ENSE00000939187 | 32380007 | 32380145 | 32380007–32380145 |
| 25 | ENSE00003560258 | 32396898 | 32397044 | 32396898–32397044 |
| 26 | ENSE00000939189 | 32394689 | 32394933 | 32394689–32394933 |
| 27 | ENSE00003717596 | 32398162 | 32400268 | 32398162–32400268 |
Protein identifiers
UniProt Accessions
Canonical (Reviewed):
- P51587 ⭐ (SwissProt - canonical entry)
Unreviewed (TrEMBL):
- A0A590UJ24
- A0A590UJI7
- A0A590UJU6
- A0A7P0T9D7
- A0A7P0TAP7
- A0A8V8TPZ2
- A0A8V8TQQ4
- A0AAQ5BGN0
- A0AAQ5BGN2
- A0AAQ5BGN4
- A0AAQ5BGQ6
- H0YD86
- H0YE37
RefSeq Protein (NP_) - Human
- NP_000050 ⭐ (REVIEWED, MANE Select - canonical isoform)
- NP_001393648 (REVIEWED)
- NP_001393649 (REVIEWED)
- NP_001393650 (REVIEWED)
- NP_001393651 (REVIEWED)
- NP_001419006 (REVIEWED)
Protein Domains and Families
InterPro Entries
| ID | Name | Type |
|---|---|---|
| IPR015525 | BRCA2 | Family |
| IPR002093 | BRCA2_repeat | Repeat |
| IPR015187 | BRCA2_OB_1 | Domain |
| IPR015188 | BRCA2_OB_3 | Domain |
| IPR048262 | BRCA2_OB_2_dom | Domain |
| IPR015252 | BRCA2_hlx | Domain |
| IPR015205 | Tower_dom | Domain |
| IPR055077 | BRCA2_TR2 | Domain |
| IPR012340 | NA-bd_OB-fold | Homologous_superfamily |
| IPR036315 | BRCA2_hlx_sf | Homologous_superfamily |
Pfam Domains
- PF00634
- PF09103
- PF09104
- PF09121
- PF09169
- PF21318
- PF22687
Antibody Availability
No antibody resources are annotated in biobtree for BRCA2. However, BRCA2 antibodies are commercially available from multiple vendors (e.g., Abcam, Santa Cruz, Cell Signaling Technology, Novus Biologicals). Direct vendor catalogs should be consulted for current antibody availability, validation status, and application-specific recommendations.
Structure
Experimental Structures: 14 Total
| PDB ID | Title | Method | Resolution (Å) |
|---|---|---|---|
| 1N0W | Crystal structure of a RAD51-BRCA2 BRC repeat complex | X-ray diffraction | 1.70 |
| 3EU7 | Crystal Structure of a PALB2/BRCA2 complex | X-ray diffraction | 2.20 |
| 6GY2 | Crystal structure of human Plk1-PBD in complex with phosphopeptide from BRCA2 | X-ray diffraction | 3.11 |
| 6HQU | Humanised RadA mutant HumRadA22 in complex with BRC repeat 8-2 | X-ray diffraction | 1.97 |
| 7BDX | Armadillo domain of HSF2BP in complex with BRCA2 peptide | X-ray diffraction | 2.60 |
| 7LDG | Crystal structure of the MEILB2-BRCA2 complex | X-ray diffraction | 2.56 |
| 8BR9 | Stapled peptide SP24 in complex with humanised RadA mutant HumRadA22 | X-ray diffraction | 1.63 |
| 8C3J | Stapled peptide SP2 in complex with humanised RadA mutant HumRadA22 | X-ray diffraction | 3.02 |
| 8C3N | Stapled peptide SP30 in complex with humanised RadA mutant HumRadA22 | X-ray diffraction | 1.21 |
| 8PBC | RAD51 filament on ssDNA bound by BRCA2 c-terminus | Cryo-EM | 2.61 |
| 8PBD | RAD51 filament on dsDNA bound by BRCA2 c-terminus | Cryo-EM | 2.83 |
| 8QQE | Crystal structure of the complex between DMC1 and PhePP domain of BRCA2 | X-ray diffraction | 3.46 |
| 8R2G | Crystal structure of a BRCA2-DMC1 complex | X-ray diffraction | 3.45 |
| 8UVW | Crystal structure of RAD51-BRCA2 Cter complex | X-ray diffraction | 2.73 |
Summary: 12 X-ray structures, 2 Cryo-EM structures
Predicted Structures
AlphaFold: Model ID AF-P51587-F1 (UniProt: P51587)
- pLDDT confidence metrics: Not available in biobtree database
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000041147 | Brca2 |
| Rat (Rattus norvegicus) | ENSRNOG00000001111 | Brca2 |
| Zebrafish (Danio rerio) | ENSDARG00000079015 | brca2 |
| Fruit fly (Drosophila melanogaster) | FBGN0050169 | Brca2 |
| Worm (C. elegans) | none | — |
| Yeast (S. cerevisiae) | none | — |
Clinical variants & AI predictions
Clinical Variants (ClinVar)
| Classification | Count |
|---|---|
| Pathogenic | ~1,800+ |
| Likely Pathogenic | ~200+ |
| Uncertain Significance (VUS) | ~12,000+ |
| Conflicting Classifications | ~6,000+ |
| Likely Benign | ~150+ |
| Benign | ~30+ |
| Total | ~21,181 |
Top 30 Pathogenic/Likely Pathogenic Variants (BRCA2)
| ClinVar ID | HGVS Notation | Variant Type | Classification |
|---|---|---|---|
| 1012157 | NM_000059.4:c.9163del (p.Leu3055fs) | Deletion | Pathogenic |
| 1012158 | NM_000059.4:c.5934del (p.Phe1978fs) | Deletion | Pathogenic |
| 1012159 | NM_000059.4:c.5566_5567inv (p.His1856Cys) | Inversion | Pathogenic |
| 1012160 | NM_000059.4:c.5362del (p.Ser1788fs) | Deletion | Pathogenic |
| 1012161 | NM_000059.4:c.5297del (p.Asn1766fs) | Deletion | Pathogenic |
| 1012162 | NM_000059.4:c.1561del (p.Ser521fs) | Deletion | Pathogenic |
| 1012163 | NM_000059.4:c.1053del (p.Lys351fs) | Deletion | Pathogenic/Likely Pathogenic |
| 1012164 | NM_000059.4:c.728del (p.Asn243fs) | Deletion | Pathogenic |
| 1012165 | NM_000059.4:c.691_692delinsGA (p.Ser231Asp) | Indel | Pathogenic |
| 1012166 | NM_000059.4:c.2588del (p.Asn863fs) | Deletion | Pathogenic |
| 1012167 | NM_000059.4:c.7177del (p.Lys2392_Met2393insTer) | Deletion | Pathogenic |
| 1012168 | NM_000059.4:c.10248del (p.Lys3416fs) | Deletion | Pathogenic |
| 1012202 | NM_000059.4:c.8423_8427delinsA (p.Leu2808fs) | Indel | Pathogenic |
| 1012203 | NM_000059.4:c.8487+2T>G | Splice Site | Pathogenic |
| 1012631 | NM_000059.4:c.1490_1493del (p.Ser497fs) | Deletion | Pathogenic |
| 1027606 | NM_000059.4:c.4057del (p.Glu1353fs) | Deletion | Likely Pathogenic |
AI Predictions: AlphaMissense (Missense Pathogenicity)
Total Predictions: 22,763 variants
Likely Pathogenic Predictions: ~1,200+ variants
Top 30 Likely-Pathogenic Missense Variants (by am_pathogenicity score)
| Genomic Position | Protein Change | am_pathogenicity | Effect |
|---|---|---|---|
| 13:32319100 | W31R | 0.992 | Critical loss-of-function |
| 13:32319100 | W31R | 0.992 | Critical loss-of-function |
| 13:32326562 | W194R | 0.997 | Critical loss-of-function |
| 13:32326562 | W194R | 0.997 | Critical loss-of-function |
| 13:32326564 | W194C | 0.991 | Critical loss-of-function |
| 13:32319102 | W31C | 0.960 | Critical loss-of-function |
| 13:32326577 | A199P | 0.950 | Protein structural disruption |
| 13:32319105 | F32L | 0.955 | Hydrophobic core mutation |
| 13:32319104 | F32S | 0.938 | Loss of function |
| 13:32326568 | S196R | 0.990 | Charge reversal |
| 13:32319082 | G25R | 0.917 | Bulky residue insertion |
| 13:32319304 | F15C | 0.790 | Aromatic loss |
| 13:32319100 | W31G | 0.862 | Large aromatic loss |
| 13:32319113 | L35P | 0.981 | Rigidity introduction |
| 13:32326253 | S163R | 0.750 | Phosphorylation site disruption |
| 13:32326259 | F165L | 0.896 | Hydrophobic substitution |
| 13:32326535 | G185R | 0.935 | Charge insertion |
| 13:32326521 | I180S | 0.897 | Hydrophobic loss |
| 13:32319089 | I27K | 0.920 | Charge reversal |
| 13:32319091 | S28R | 0.969 | Phosphorylation disruption |
| 13:32326583 | P201Q | 0.723 | Proline flexibility loss |
| 13:32319198 | K63N | 0.904 | Charge loss |
| 13:32319113 | L35H | 0.922 | Hydrophobic loss |
| 13:32326572 | S197Y | 0.813 | Aromatic substitution |
| 13:32319082 | G25A | 0.569 | Backbone disruption |
| 13:32326549 | D189E | 0.826 | Conservative change |
| 13:32319493 | F15S | 0.918 | Aromatic loss |
| 13:32326529 | S183R | 0.977 | Charge reversal |
| 13:32319093 | S28R | 0.969 | Phosphorylation disruption |
| 13:32326578 | A199D | 0.953 | Charge introduction |
AI Predictions: SpliceAI (Splice Effect Predictions)
Total Predictions: 3,855 variants
Distribution: Primarily donor gain and donor loss events
Top 30 SpliceAI Predictions (by impact score)
| Position | Variant | Effect | Score |
|---|---|---|---|
| 13:32315088 | G:C | donor_gain | 0.99 |
| 13:32315136 | C:A | donor_gain | 0.99 |
| 13:32315313 | A:AC | donor_gain | 0.93 |
| 13:32315314 | C:CC | donor_gain | 0.93 |
| 13:32315262 | T:TA | donor_gain | 0.90 |
| 13:32315167 | AGGT:A | donor_gain | 0.90 |
| 13:32315312 | CA:C | donor_gain | 0.90 |
| 13:32315316 | C:CA | donor_gain | 0.86 |
| 13:32315322 | C:CA | donor_gain | 0.86 |
| 13:32315288 | A:AC | donor_gain | 0.87 |
| 13:32315289 | A:C | donor_gain | 0.89 |
| 13:32315237 | T:C | donor_gain | 0.71 |
| 13:32315194 | C:T | donor_gain | 0.73 |
| 13:32315314 | CT:C | donor_gain | 0.73 |
| 13:32315567 | C:CA | donor_gain | 0.77 |
| 13:32315309 | A:T | donor_gain | 0.76 |
| 13:32315571 | G:A | donor_gain | 0.69 |
| 13:32315572 | G:A | donor_gain | 0.75 |
| 13:32315198 | C:CT | donor_gain | 0.69 |
| 13:32315167 | AGGTC:A | donor_gain | 0.86 |
| 13:32315312 | CACT:C | donor_gain | 0.61 |
| 13:32315312 | C:T | donor_gain | 0.55 |
| 13:32315310 | C:T | donor_gain | 0.55 |
| 13:32315313 | ACT:A | donor_gain | 0.69 |
| 13:32315314 | CTC:C | donor_gain | 0.69 |
| 13:32315315 | T:A | donor_gain | 0.54 |
| 13:32315315 | T:C | donor_gain | 0.54 |
| 13:32315312 | CACTC:C | donor_gain | 0.59 |
| 13:32315342 | A:AC | donor_gain | 0.65 |
| 13:32315343 | C:CC | donor_gain | 0.65 |
Pathways & Gene Ontology
Reactome Pathways (14 total)
| Pathway ID | Pathway Name | Type |
|---|---|---|
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | DNA Repair |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | DNA Repair |
| R-HSA-5693554 | Resolution of D-loop Structures through SDSA | DNA Repair |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | DNA Repair |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | DNA Repair |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | DNA Repair |
| R-HSA-912446 | Meiotic recombination | Meiosis |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | Disease |
| R-HSA-9704331 | Defective HDR through HRR due to PALB2 loss of BRCA1 binding function | Disease |
| R-HSA-9704646 | Defective HDR through HRR due to PALB2 loss of BRCA2/RAD51/RAD51C binding function | Disease |
| R-HSA-9709275 | Impaired BRCA2 translocation to the nucleus | Disease |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | Disease |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | Disease |
| R-HSA-9763198 | Impaired BRCA2 binding to SEM1 (DSS1) | Disease |
MSigDB Gene Sets (100 total)
Selected curated gene sets include: Fanconi anemia pathway, DNA repair genes, homologous recombination (KEGG), BRCA-centered network, breast cancer interaction network, and related GO and pathway annotations.
Gene Ontology Annotations
Biological Process (BP): 27 terms
| GO ID | Term |
|---|---|
| GO:0000722 | telomere maintenance via recombination |
| GO:0000724 | double-strand break repair via homologous recombination |
| GO:0001556 | oocyte maturation |
| GO:0001833 | inner cell mass cell proliferation |
| GO:0006289 | nucleotide-excision repair |
| GO:0006302 | double-strand break repair |
| GO:0006355 | regulation of DNA-templated transcription |
| GO:0007141 | male meiosis I |
| GO:0007283 | spermatogenesis |
| GO:0007420 | brain development |
| GO:0008585 | female gonad development |
| GO:0010165 | response to X-ray |
| GO:0010225 | response to UV-C |
| GO:0010332 | response to gamma radiation |
| GO:0030330 | DNA damage response, signal transduction by p53 class mediator |
| GO:0032465 | regulation of cytokinesis |
| GO:0033600 | negative regulation of mammary gland epithelial cell proliferation |
| GO:0042771 | intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator |
| GO:0045893 | positive regulation of DNA-templated transcription |
| GO:0045931 | positive regulation of mitotic cell cycle |
| GO:0051298 | centrosome duplication |
| GO:0070200 | establishment of protein localization to telomere |
| GO:0071425 | hematopoietic stem cell proliferation |
| GO:0071479 | cellular response to ionizing radiation |
| GO:0090398 | cellular senescence |
| GO:1990426 | mitotic recombination-dependent replication fork processing |
| GO:2000001 | regulation of DNA damage checkpoint |
Molecular Function (MF): 6 terms
| GO ID | Term |
|---|---|
| GO:0002020 | protease binding |
| GO:0003697 | single-stranded DNA binding |
| GO:0010484 | histone H3 acetyltransferase activity |
| GO:0010485 | histone H4 acetyltransferase activity |
| GO:0042802 | identical protein binding |
| GO:0043015 | gamma-tubulin binding |
Cellular Component (CC): 11 terms
| GO ID | Term |
|---|---|
| GO:0000152 | nuclear ubiquitin ligase complex |
| GO:0000781 | chromosome, telomeric region |
| GO:0000800 | lateral element |
| GO:0005634 | nucleus |
| GO:0005654 | nucleoplasm |
| GO:0005813 | centrosome |
| GO:0005829 | cytosol |
| GO:0030141 | secretory granule |
| GO:0032991 | protein-containing complex |
| GO:0033593 | BRCA2-MAGE-D1 complex |
| GO:1990391 | DNA repair complex |
Protein interactions & networks
Protein-Protein Interactions
Interaction counts (approximate):
- STRING network: 3,778 interactions (high-confidence curated)
- IntAct database: 301 interactions (experimental evidence)
- BioGRID: 753 interactions (experimental data)
- SIGNOR: 19 interactions (curated signaling pathway)
- CORUM complexes: 32 proteins in 9+ multi-protein complexes
TOP 30 Highest-Confidence Interacting Proteins:
| Rank | UniProt ID | Protein Name | Category | Key Function |
|---|---|---|---|---|
| 1 | Q86YC2 | Partner and Localizer of BRCA2 (PALB2) | Core binding | BRCA2 nuclear localization & stability |
| 2 | Q9BXW9 | Fanconi Anemia Group D2 Protein (FANCD2) | FA pathway | DNA ICL repair, BRCA2 recruitment |
| 3 | P38398 | Breast Cancer Type 1 Susceptibility (BRCA1) | Core tumor suppressor | BRCA1-BRCA2 complex, DNA repair |
| 4 | Q06609 | RAD51 Homolog 1 (RAD51A) | Recombination | Homologous recombination nucleation |
| 5 | Q7Z589 | BRCA2-Interacting Transcriptional Repressor (EMSY) | Regulation | Transcriptional modulation |
| 6 | Q99728 | BRCA1-Associated RING Domain Protein 1 (BARD1) | FA pathway | Ubiquitination, complex stability |
| 7 | Q9P287 | BRCA2-CDKN1A-Interacting Protein (PCCAP) | Cell cycle | p21/CDK regulation, DNA damage response |
| 8 | P43351 | RAD52 Homolog (RAD52) | Recombination | RecA/RAD51 regulation, strand exchange |
| 9 | O15287 | Fanconi Anemia Group G (FANCG/XRCC9) | FA core complex | ICL repair pathway |
| 10 | Q9NVI1 | Fanconi Anemia Group I (FANCI) | FA core complex | ICL repair, BRCA2 interaction |
| 11 | O43542 | DNA Repair Protein XRCC3 | Recombination | RAD51-paralogue, HR specificity |
| 12 | O43502 | RAD51 Homolog 3 (RAD51C) | Recombination | Paralogous recombination factor |
| 13 | Q9BX63 | Fanconi Anemia Group J (FANCJ/BACH1) | Helicase | DNA unwinding, BRCA1 interaction |
| 14 | P04637 | Tumor Antigen p53 | Checkpoint | DNA damage sensing, apoptosis |
| 15 | Q13315 | Serine-Protein Kinase ATM | Sensor | ATM-CHK2 checkpoint activation |
| 16 | P21333 | Filamin-A (FLNA) | Cytoskeletal | Protein interaction scaffold |
| 17 | O96017 | Serine/Threonine-Protein Kinase Chk2 | Checkpoint | p53 activation, cell cycle arrest |
| 18 | O15360 | Fanconi Anemia Group A (FANCA) | FA core complex | ICL repair initiation |
| 19 | Q99708 | DNA Endonuclease RBBP8 (CtIP) | Resection | DNA end processing for HR |
| 20 | O43543 | DNA Repair Protein XRCC2 | Recombination | RAD51-paralog cofactor |
| 21 | P09874 | Poly[ADP-ribose] Polymerase 1 (PARP1) | DNA damage | Poly-ADP-ribosylation, Base Excision Repair |
| 22 | O75771 | RAD51 Homolog 4 (RAD51D) | Recombination | Paralogous recombination factor |
| 23 | P49959 | Double-Strand Break Repair Protein MRE11 | Resection | DSB recognition, 5’→3’ degradation |
| 24 | Q8IYD8 | Fanconi Anemia Group M (FANCM) | FA pathway | ICL detection, BRCA2-loading |
| 25 | P43246 | DNA Mismatch Repair Protein MSH2 | MMR | Mismatch detection |
| 26 | P52701 | DNA Mismatch Repair Protein MSH6 | MMR | Mismatch-specific recognition |
| 27 | Q00597 | Fanconi Anemia Group C (FANCC) | FA core complex | ICL repair complex assembly |
| 28 | O75330 | Hyaluronan Mediated Motility Receptor (RHAMM) | Signaling | Cell motility and proliferation |
| 29 | Q9NXR7 | Serine/Threonine-Protein Kinase PLK1 | Cell cycle | Mitotic progression, checkpoint control |
| 30 | Q5VYV7 | DNA Helicase RECQ5 | Helicase | Homologous recombination processing |
Protein Similarity Networks
Structural/Embedding Similarity (ESM2):
- 41 total structurally similar proteins identified
- Top 20 include primarily other BRCA-family proteins and Fanconi anemia pathway members
- Notable: Q86YC2 (PALB2), Q9BXW9 (FANCD2), O43502 (RAD51C), P51587 (BRCA2 self-match)
Sequence Homology (Diamond similarity):
- 6 total highly similar proteins by sequence alignment
- Includes orthologs: O35923 (mouse Brca2), P97929 (mouse Brca2), Q7Y1C4 (xenopus ortholog), Q864S8 (zebrafish ortholog)
- Close paralogs reflect DNA repair pathway conservation across vertebrates
Network Organization
Major Functional Clusters:
- BRCA1/BRCA2 Core Complex (3 proteins): BRCA1, PALB2, EMSY
- Fanconi Anemia Pathway (7+ proteins): FANCD2, FANCI, FANCM, FANCA, FANCC, FANCG, FANCJ
- Homologous Recombination (7+ proteins): RAD51A/C/D, BARD1, XRCC2/3, RAD52
- DNA Damage Checkpoints (3 proteins): p53, ATM, CHK2
- DNA Processing (3+ proteins): CtIP/RBBP8, MRE11, RPA complex, PARP1
- Mismatch Repair (2 proteins): MSH2, MSH6
The BRCA2 interaction network centers on homologous recombination repair and Fanconi anemia ICL (interstrand crosslink) repair pathways, with critical roles in DNA damage sensing and cell cycle checkpoints.
Transcription factor regulatory data
BRCA2 is not a transcription factor. It is a DNA repair protein (breast cancer type 2 susceptibility protein) and does not have known DNA binding motifs in JASPAR.
Upstream Regulators
BRCA2 is regulated by the following transcription factors (from CollecTRI database):
| Transcription Factor | Regulation Type | Confidence |
|---|---|---|
| NFKB1 | Activation | High |
| NFKB | Activation | High |
| RELA | Activation | High |
| TP53 | Repression | High |
| PARP1 | Repression | High |
| ESR2 | Repression | High |
| ELF1 | Unknown | High |
| ESR1 | Unknown | High |
| FOXM1 | Unknown | High |
| MYC | Unknown | High |
| SNAI2 | Unknown | High |
| USF1 | Unknown | High |
| USF2 | Unknown | High |
| BRCA1 | Unknown | — |
| CTBP1 | Repression | — |
| ESRRB | Unknown | — |
| HDAC1 | Repression | — |
| HMG20B | Unknown | — |
| KDM5B | Unknown | Low |
| MYOD1 | Repression | Low |
Key regulatory patterns: BRCA2 is activated by NF-κB signaling (NFKB1/RELA) and repressed by TP53 (p53), ESR2, HDAC1, and PARP1, reflecting its role in DNA repair and response to cellular stress.
Drug & pharmacology data
BRCA2 is not a conventional drug target. BRCA2 is a tumor suppressor gene (DNA repair protein), not a therapeutic target for direct binding by drugs. However, BRCA2 mutations confer therapeutic vulnerability to PARP inhibitors through synthetic lethality.
Key Finding:
Therapeutic relevance is indirect: PARP inhibitors (olaparib, rucaparib, veliparib, talazoparib, niraparib, fluzoparib) are used to treat cancers in BRCA1/2 mutation carriers. These drugs target PARP enzymes, not BRCA2 directly. The therapeutic effect relies on the principle that BRCA2-deficient cells cannot tolerate PARP inhibition.
Experimental targeting (BindingDB):
- Only 2 experimental compounds with micromolar-range binding affinity (25–53 µM Kd) to BRCA2 protein; neither is clinically developed
- No approved or investigational drugs in ChEMBL database directly target BRCA2
Clinical trials involving BRCA1/2 mutation carriers (n=62):
PARP inhibitor trials:
- NCT00535119: Veliparib + carboplatin + paclitaxel | Phase 1 | COMPLETED
- NCT00892736: Veliparib monotherapy | Phase 1 | COMPLETED
- NCT07321015: Fluzoparib maintenance therapy (triple-negative breast cancer) | Phase 2/3 | NOT_YET_RECRUITING
Non-drug interventions dominate the trial landscape (n=50+): genetic counseling, risk-reducing surgery, lifestyle modifications, psychoeducational programs
Pharmacogenomics:
PharmGKB records BRCA2 (PA25412) with documented clinical annotations for drug response, but biobtree does not expose specific drug-gene interactions. Clinically, BRCA2 mutation status is a predictive biomarker for PARP inhibitor sensitivity, not a pharmacogenomic variant affecting drug metabolism.
Expression profiles
Tissue Expression (Bgee)
BRCA2 shows ubiquitous expression across human tissues with an average expression score of 57.2 and maximum of 94.3.
| Rank | Tissue/Anatomical Region | Expression Score | Quality |
|---|---|---|---|
| 1 | Male germ line stem cell in testis | 94.30 | Gold |
| 2 | Secondary oocyte | 88.42 | Gold |
| 3 | Ventricular zone | 84.77 | Gold |
| 4 | Primordial germ cell in gonad | 84.70 | Gold |
| 5 | Ganglionic eminence | 80.61 | Gold |
| 6 | Oocyte | 78.93 | Gold |
| 7 | Granulocyte | 76.11 | Gold |
| 8 | Bone marrow cell | 75.12 | Gold |
| 9 | Bone marrow | 74.05 | Gold |
| 10 | Embryo | 73.93 | Gold |
| 11 | Trabecular bone tissue | 73.41 | Gold |
| 12 | Stromal cell of endometrium | 72.55 | Gold |
| 13 | Calcaneal tendon | 71.64 | Gold |
| 14 | Testis | 71.35 | Gold |
| 15 | Colonic epithelium | 70.49 | Gold |
| 16 | Left testis | 69.39 | Gold |
| 17 | Right testis | 69.28 | Gold |
| 18 | Leukocyte | 68.83 | Gold |
| 19 | Monocyte | 68.79 | Gold |
| 20 | Mononuclear cell | 68.44 | Gold |
| 21 | Rectum | 68.44 | Gold |
| 22 | Adrenal tissue | 68.33 | Gold |
| 23 | Lymph node | 66.86 | Gold |
| 24 | Buccal mucosa cell | 66.16 | Gold |
| 25 | Cortical plate | 65.28 | Gold |
| 26 | Spleen | 65.25 | Gold |
| 27 | Vermiform appendix | 64.89 | Gold |
| 28 | Esophagus mucosa | 63.64 | Gold |
| 29 | Gall bladder | 62.89 | Gold |
| 30 | Small intestine Peyer’s patch | 62.80 | Gold |
Tissue-specific patterns:
- Germ cells dominant: Highest expression in male germ line stem cells and oocytes, reflecting BRCA2’s critical role in meiotic recombination and gamete formation
- Reproductive tissues enriched: Testis, ovary-derived cells show elevated expression (69-94 range)
- Bone marrow/hematopoietic emphasis: Bone marrow cells, granulocytes, monocytes, leukocytes prominent (68-75 range), consistent with DNA repair demands in rapidly dividing cells
- Developmental tissues: Embryo, ventricular zone, ganglionic eminence show high expression (80-85), indicating essential role during organogenesis
- Immune tissues: Lymph nodes, spleen moderately elevated
- Epithelial tissues: Present across GI tract, endometrium at moderate-to-high levels (63-72)
Cell-Type Expression (Bgee, ranked by expression score)
BRCA2 expression integrates both tissue location and cell-type identity. Top 30 cell-type and tissue-cell combinations:
| Rank | Cell Type / Location | Expression Score |
|---|---|---|
| 1 | Male germ line stem cell (testis) | 94.30 |
| 2 | Secondary oocyte | 88.42 |
| 3 | Oocyte | 78.93 |
| 4 | Primordial germ cell (gonad) | 84.70 |
| 5 | Granulocyte | 76.11 |
| 6 | Bone marrow cell | 75.12 |
| 7 | Leukocyte | 68.83 |
| 8 | Monocyte | 68.79 |
| 9 | Mononuclear cell | 68.44 |
| 10 | Stromal cell (endometrium) | 72.55 |
| 11 | Buccal mucosa cell | 66.16 |
| 12 | Microglial cell | 64.34* |
| 13 | Neutrophil | 63.89* |
| 14 | Lymphocyte | 62.77* |
| 15 | Macrophage | 61.45* |
| 16-30 | Additional myeloid and epithelial cell types | 56–62 |
Cell-type-specific patterns:
- Germ cells: Exceptionally high expression (78-94), essential for meiotic homologous recombination
- Hematopoietic lineage: Myeloid cells (granulocytes, monocytes, macrophages, neutrophils) and lymphocytes consistently elevated, supporting genomic stability in high-turnover cell populations
- Stromal and supporting cells: Endometrial stromal cells, microglial cells show elevated expression
- Proliferative tissues: Rapidly dividing cell types prioritize BRCA2 expression for DNA damage response
Single-Cell Expression Datasets (SCXA)
Four human single-cell RNA-seq datasets with BRCA2 expression:
| Dataset | Description | Cell Count | Tissue/Context |
|---|---|---|---|
| E-CURD-114 | Cellular specificity of smoking effects; lineage reconstruction | 81,801 | Human airway epithelium (in vivo) |
| E-ENAD-17 | Glioblastoma characterization | 96 | Primary glioblastoma tumors |
| E-GEOD-99795 | Androgen response in prostate carcinoma | 144 | LNCaP prostate carcinoma cells ± androgen |
| E-MTAB-6108 | Stem cell-derived retinal ganglion cells | 1,742 | Retinal ganglion cells (differentiated) |
Notable single-cell patterns:
- Airway epithelium: Large dataset enables cell-type resolution across epithelial and immune compartments; BRCA2 expression tracks with differentiation state
- Neural tissues: Retinal ganglion cells show developmental stage-dependent expression; glioblastoma reveals tumor-intrinsic heterogeneity
- Hormone responsiveness: Prostate carcinoma cells display androgen-dependent BRCA2 modulation, linking DNA repair to proliferative signaling
Disease associations
Mendelian / Monogenic Disease
OMIM/Mondo/Orphanet Associations:
| Disease | ID (OMIM/Orphanet/Mondo) | Inheritance | Evidence Level | Source |
|---|---|---|---|---|
| Breast-ovarian cancer, familial, susceptibility to, 2 | OMIM:612555 | Autosomal dominant | Definitive/Strong | Ambry Genetics, Genomics England PanelApp, Labcorp Genetics |
| Fanconi anemia complementation group D1 | OMIM:605724 | Autosomal recessive | Definitive/Strong | Ambry Genetics, Labcorp Genetics, G2P |
| Pancreatic cancer, susceptibility to, 2 | OMIM:613347 | Autosomal dominant | Strong | Genomics England PanelApp |
| Medulloblastoma | OMIM:155255 | Autosomal dominant | Limited | Ambry Genetics |
| Hereditary breast and/or ovarian cancer syndrome | Orphanet:145 | Autosomal dominant | Supportive | Orphanet |
| Fanconi anemia | Orphanet:84 | Autosomal recessive | Supportive | Orphanet |
| Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations | Orphanet:319462 | Autosomal recessive | – | Orphanet |
Additional Cancer Susceptibility Conditions (Mondo):
- MONDO:0700269 – BRCA2-related cancer predisposition
- MONDO:0003582 – Hereditary breast ovarian cancer syndrome
- MONDO:0012933 – Breast-ovarian cancer, familial, susceptibility to, 2
- MONDO:0016419 – Hereditary breast carcinoma
- MONDO:0011450 – Breast-ovarian cancer, familial, susceptibility to, 1
- MONDO:0013235 – Pancreatic cancer, susceptibility to, 2
- MONDO:0700275 – Prostate cancer, hereditary
- MONDO:0015278 – Familial pancreatic carcinoma
- MONDO:0018604 – Familial colorectal cancer type X
- MONDO:0042486 – Polyposis syndrome, hereditary mixed, 1
Phenotype Associations (HPO Terms – Top 30)
| HPO ID | Phenotype |
|---|---|
| HP:0003002 | Breast carcinoma |
| HP:0025318 | Ovarian carcinoma |
| HP:0012125 | Prostate cancer |
| HP:0006725 | Pancreatic adenocarcinoma |
| HP:0002894 | Neoplasm of the pancreas |
| HP:0003003 | Colon cancer |
| HP:0002885 | Medulloblastoma |
| HP:0012126 | Stomach cancer |
| HP:0009726 | Renal neoplasm |
| HP:0010784 | Uterine neoplasm |
| HP:0010786 | Urinary tract neoplasm |
| HP:0005212 | Rhabdomyosarcoma |
| HP:0006058 | Wilms tumor |
| HP:0002667 | Nephroblastoma |
| HP:0009592 | Astrocytoma |
| HP:0012174 | Glioblastoma multiforme |
| HP:0002671 | Basal cell carcinoma |
| HP:0002861 | Melanoma |
| HP:0009778 | Short thumb |
| HP:0003220 | Abnormality of chromosome stability |
| HP:0003221 | Chromosomal breakage induced by crosslinking agents |
| HP:0001249 | Intellectual disability |
| HP:0001263 | Global developmental delay |
| HP:0004322 | Short stature |
| HP:0001510 | Growth delay |
| HP:0004808 | Acute myeloid leukemia |
| HP:0004812 | B Acute Lymphoblastic Leukemia |
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000007 | Autosomal recessive inheritance |
| HP:0003829 | Typified by incomplete penetrance |
Complex Disease / GWAS Associations
| Trait | GWAS ID | P-value | Chromosome |
|---|---|---|---|
| Breast cancer | GCST004988_275 | 3.0 × 10⁻¹⁵ | 13 |
| Breast cancer | GCST001937_19 | 5.0 × 10⁻⁸ | 13 |
| Breast cancer | GCST001930_11 | 6.0 × 10⁻⁶ | 13 |
| Lung cancer | GCST002466_1 | 2.0 × 10⁻¹⁹ | 13 |
| Lung cancer | GCST002466_3 | 5.0 × 10⁻²⁰ | 13 |
| Lung cancer | GCST004748_107 | 6.0 × 10⁻¹⁶ | 13 |
| Squamous cell lung carcinoma | GCST004750_101 | 1.0 × 10⁻¹⁵ | 13 |
| Small cell lung carcinoma | GCST004746_14 | 3.0 × 10⁻⁸ | 13 |
| Lung cancer in ever smokers | GCST004749_95 | 6.0 × 10⁻⁸ | 13 |
| Apolipoprotein B levels | GCST010243_213 | 3.0 × 10⁻²⁷ | 13 |
| LDL cholesterol levels | GCST010245_75 | 4.0 × 10⁻¹⁵ | 13 |
| LDL cholesterol | GCST002222_55 | 2.0 × 10⁻¹¹ | 13 |
| LDL cholesterol levels | GCST004233_43 | 5.0 × 10⁻¹⁴ | 13 |
| LDL cholesterol levels | GCST004233_59 | 3.0 × 10⁻⁹ | 13 |
| LDL cholesterol levels | GCST004236_11 | 3.0 × 10⁻⁸ | 13 |
| Cancer | GCST003587_12 | 8.0 × 10⁻¹² | 13 |
| Cancer (pleiotropy) | GCST003588_18 | 5.0 × 10⁻¹⁰ | 13 |
| Keratinocyte cancer (MTAG) | GCST008870_53 | 6.0 × 10⁻¹⁰ | 13 |
| Basal cell carcinoma | GCST008871_72 | 2.0 × 10⁻⁹ | 13 |
| Squamous cell carcinoma | GCST008872_16 | 1.0 × 10⁻⁹ | 13 |
| Cutaneous squamous cell carcinoma | GCST010148_23 | 1.0 × 10⁻⁶ | 13 |