BARD1 Gene: BRCA1-Associated RING Domain Protein 1
A critical tumor suppressor gene involved in DNA repair, cell cycle regulation, and hereditary cancer susceptibility.
Gene Information Card
| Symbol | BARD1 |
|---|---|
| Full Name | BRCA1-associated RING domain protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 580 ncbi.nlm.nih.gov/gene/580 |
| Ensembl ID | ENSG00000138376 |
| UniProt ID | Q99728 |
| OMIM ID | 601593 |
| HGNC ID | 952 |
| Aliases | BRCA1-associated RING domain protein 1; RING finger protein 65; RNF65 |
Description
The BARD1 gene encodes a protein that interacts with BRCA1 to form a heterodimeric complex essential for DNA double-strand break repair, homologous recombination, and cell cycle checkpoint control. BARD1 contains a RING finger domain, ankyrin repeats, and a BRCT domain, which are critical for its tumor suppressor functions. Germline mutations in BARD1 are associated with increased susceptibility to breast and ovarian cancers, and somatic alterations are observed in various tumor types.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of function mutations in BARD1 impair homologous recombination repair, leading to genomic instability and tumorigenesis. | ClinVar; OMIM; multiple case-control studies |
| Ovarian cancer | BARD1 mutations disrupt BRCA1-BARD1 complex formation, compromising DNA repair and increasing cancer risk. | ClinVar; OMIM; functional studies |
| Endometrial cancer | Somatic BARD1 alterations may contribute to tumor progression through defective DNA damage response. | COSMIC; literature |
| Neuroblastoma | BARD1 variants have been implicated in neuroblastoma susceptibility, possibly through altered apoptosis regulation. | OMIM; GWAS studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 8.2 | Low |
| Ovary | 6.5 | Low |
| Testis | 12.3 | Medium |
| Bone marrow | 5.1 | Low |
| Lung | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 7.5 | Moderate expression |
| OVCAR3 (ovarian cancer) | 6.0 | Moderate expression |
| A549 (lung cancer) | 4.2 | Low expression |
| HEK293 (embryonic kidney) | 9.8 | High expression (transfected) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1690C>T (p.Gln564Ter) | Nonsense | Rare (0.1% in general population) | Truncated protein, loss of function, increased cancer risk |
| c.1315C>T (p.Arg439Trp) | Missense | Rare (0.05%) | Impaired BRCA1 binding, reduced DNA repair activity |
| c.1921C>T (p.Arg641Ter) | Nonsense | Rare (0.02%) | Premature stop codon, loss of function |
| c.1977C>A (p.Tyr659Ter) | Nonsense | Rare (0.01%) | Loss of BRCT domain, defective DNA damage response |
Mutation functional classification
Loss of Function (LOF)
Most BARD1 pathogenic mutations are loss-of-function, leading to truncated or unstable proteins that fail to interact with BRCA1 or localize to DNA damage sites, thereby impairing homologous recombination repair.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for BARD1; oncogenic activity is primarily associated with loss of tumor suppressor function.
Dominant Negative (DN)
Some missense mutations in the RING domain may exert dominant-negative effects by forming non-functional heterodimers with BRCA1, interfering with wild-type BARD1 activity.
View complete mutation data：
Gene Ontology (GO)
| • DNA repair | • double-strand break repair |
| • homologous recombination | • ubiquitin-protein transferase activity |
| • zinc ion binding | • protein heterodimerization activity |
| • cell cycle checkpoint | • apoptotic process |
| • regulation of transcription by RNA polymerase II |
Pathways
• Homologous recombination repair
• BRCA1-BARD1 complex pathway
• DNA damage response
• Cell cycle checkpoint control
• Ubiquitin-mediated proteolysis
Protein Summary
The BARD1 protein is a 777-amino acid polypeptide that forms a stable heterodimer with BRCA1 via its RING finger domain. This complex possesses E3 ubiquitin ligase activity, which is crucial for DNA damage signaling and repair. BARD1 also contains ankyrin repeats and a BRCT domain that mediate protein-protein interactions and contribute to its role in transcriptional regulation and apoptosis. Loss of BARD1 function leads to genomic instability and cancer predisposition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BARD1 (p.V507M) Point Mutation in HAP1 Cell Line | EDC03404 | Human | 580 | Details Get a Quote |
| BARD1 (p.R378S) Point Mutation in HAP1 Cell Line | EDC03405 | Human | 580 | Details Get a Quote |
| BARD1 (p.T351=) Point Mutation in HAP1 Cell Line | EDC03406 | Human | 580 | Details Get a Quote |
| BARD1 (c.2001+66A>C )Point Mutation in HAP1 Cell Line | EDC03403 | Human | 580 | Details Get a Quote |
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