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BARD1
BRCA1 associated RING domain 1
The BARD1 gene provides instructions for making a protein that plays a critical role in DNA repair and tumour suppression, often working in conjunction with the BRCA1 protein. The BARD1 gene is essential for maintaining genomic stability and preventing uncontrolled cell growth.
BARD1 is located on the long (q) arm of chromosome 2, at band 2q35. Arm ratio per GRCh38 - banding schematic.
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Overview
The BARD1 gene, or BRCA1 associated RING domain 1, is crucial for cellular health and preventing disease. This gene encodes a protein that participates in several key cellular processes, including DNA repair, cell cycle control, and programmed cell death (apoptosis). Its intimate functional relationship with the BRCA1 protein is fundamental to the body's defence against DNA damage and the development of tumours.
Pathogenic variants in the BARD1 gene can disrupt its normal function, leading to impaired DNA repair mechanisms. This can result in an accumulation of errors in the genetic code, which increases the risk of developing certain inherited cancers. Specifically, BARD1 is associated with hereditary breast and ovarian cancer predisposition, placing it within the category of cancer predisposition genes.
What the gene does
The BARD1 gene encodes a protein that acts as a tumour suppressor, primarily through its interaction with the BRCA1 protein. Together, the BARD1 and BRCA1 proteins form a complex that is central to the homologous recombination pathway of DNA repair, a high-fidelity mechanism for fixing double-strand breaks in DNA [PMID:10037740]. Without this complex, DNA damage can persist, leading to genomic instability and a higher likelihood of cancerous transformations.
Beyond its role in DNA repair, the BARD1 protein also influences cell cycle progression. It is involved in ubiquitin ligase activity, which helps to regulate protein degradation and ensure proper cell division. This regulatory role contributes to its tumour suppressive capabilities by preventing the uncontrolled proliferation of damaged cells [PMID:19019808]. Furthermore, BARD1 may play a part in mediating apoptosis, or programmed cell death, in response to severe DNA damage, thereby eliminating potentially harmful cells before they can become cancerous.
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Chromosome location
The BARD1 gene is situated on the long arm of chromosome 2, specifically at position 2q35. As an autosomal gene, BARD1 is present in two copies in most individuals, one inherited from each parent. The protein produced from the BARD1 gene has a length of 777 amino acids.
Protein structure
The BARD1 protein is characterised by several distinct domains and regions that facilitate its diverse functions. At the N-terminus, there is a Disordered region (amino acids 1-32), followed by a crucial Interaction with BRCA1 region (amino acids 26-119). Within this interaction region, a RING-type (Zinc finger) domain is present (amino acids 50-87), which is critical for its E3 ubiquitin ligase activity. Further along the protein are additional Disordered regions (amino acids 167-211 and 356-404).
The central part of the protein contains several Ankyrin (ANK) repeats, including ANK 1 (amino acids 427-459), ANK 2 (amino acids 460-492), ANK 3 (amino acids 493-525), and a degenerate ANK 4 (amino acids 526-546). These ANK repeats are typically involved in protein-protein interactions. A Flexible linker region (amino acids 554-558) precedes the two C-terminal BRCT domains: BRCT 1 (amino acids 560-653) and BRCT 2 (amino acids 667-777). These BRCT domains are commonly found in proteins involved in DNA damage response and cell cycle checkpoint control [PMID:11151662].
Key variants
Variants in the BARD1 gene can impact its ability to perform its essential functions in DNA repair and tumour suppression. These genetic changes can range from single nucleotide alterations to larger deletions or insertions within the gene sequence. Depending on their nature and location, variants may lead to a non-functional protein, a protein with reduced activity, or an altered protein incapable of interacting correctly with BRCA1 or other cellular components.
Individuals carrying pathogenic or likely pathogenic variants in BARD1 may have an increased predisposition to certain cancers. The inheritance pattern for conditions associated with BARD1 is autosomal dominant, meaning that only one copy of an altered gene is sufficient to increase cancer risk.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1002del | p.Arg335fs | Pathogenic | ★★☆☆ | Familial cancer of breast |
c.1003A>T | p.Arg335Ter | Pathogenic | ★★☆☆ | Familial cancer of breast |
c.100dup | p.Trp34fs | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1014del | p.Ser339fs | Pathogenic | ★★☆☆ | not provided |
c.101G>A | p.Trp34Ter | Pathogenic | ★★☆☆ | Familial cancer of breast |
c.1021dup | p.Leu341fs | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1023del | p.Ser342fs | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.102G>A | p.Trp34Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1048C>T | p.Gln350Ter | Pathogenic | ★★☆☆ | Familial cancer of breast |
c.105_135del | p.His36fs | Pathogenic | ★★☆☆ | Familial cancer of breast |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the BARD1 gene are associated with an increased predisposition to various inherited conditions, primarily within the spectrum of hereditary cancers. While no specific individual diseases are listed for BARD1 in this database, its crucial role in DNA repair pathways means that changes to this gene can significantly elevate cancer risk. This gene is classified under the 'Cancer Predisposition' category.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic BARD1 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
In the UK, the BARD1 gene is recognised within national genomic testing programmes. It is included on the NHS Genomic Medicine Service's PanelApp for Familial breast cancer (green status) and Inherited breast cancer and ovarian cancer (green status, R208 code). This indicates that there is strong evidence for an association between BARD1 variants and these conditions, and that testing for this gene is routinely offered when clinically appropriate.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
General health practices, such as a balanced diet rich in fruits and vegetables, regular physical activity, maintaining a healthy weight, and limiting alcohol consumption, are beneficial for the general population. While there is no conclusive evidence that specific lifestyle interventions can prevent cancer in individuals with BARD1 variants, these practices are generally encouraged as part of a comprehensive health management plan for those with an increased genetic risk, alongside regular medical screenings and discussions with healthcare professionals.
Supplement considerations
While diverse supplements are marketed for general health, there is currently no conclusive scientific evidence that any specific supplement can prevent or treat conditions associated with BARD1 gene variants. Individuals considering any supplements should consult with a healthcare professional to discuss potential interactions or side effects and to ensure it aligns with their overall health plan. Supplements should not replace established medical treatments or cancer screening guidelines for those with an inherited cancer predisposition.
Frequently asked questions
What is the BARD1 gene?
The BARD1 gene provides instructions for making a protein that works closely with the BRCA1 protein to repair damaged DNA and prevent the uncontrolled growth of cells, thereby acting as a tumour suppressor.
What happens if there is a variant in the BARD1 gene?
Variants in the BARD1 gene can impair its ability to repair DNA effectively, which can lead to an accumulation of genetic errors and increase an individual's risk of developing certain inherited cancers, particularly breast and ovarian cancer.
How is BARD1 inherited?
BARD1-associated conditions are inherited in an autosomal dominant pattern. This means that inheriting just one altered copy of the BARD1 gene from either parent is sufficient to increase cancer risk.
Is BARD1 included in genetic testing in the UK?
Yes, BARD1 is recognised in the UK's NHS Genomic Medicine Service and is included on national PanelApp lists for familial breast cancer and inherited breast and ovarian cancer, indicating its relevance for clinical genetic testing.
Can lifestyle changes prevent cancer if I have a BARD1 variant?
While no specific lifestyle changes are proven to prevent cancer in individuals with BARD1 variants, general healthy lifestyle practices like a balanced diet and regular exercise are recommended for overall well-being. These should be discussed in the context of a comprehensive health plan with a healthcare provider.