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RAD51C
RAD51 paralog C
The RAD51C gene provides instructions for making a protein critical to DNA repair, and variants in this gene are associated with an elevated risk of developing specific cancers. RAD51C encodes a protein that plays a vital role in maintaining genomic stability through the homologous recombination pathway of DNA repair.
RAD51C is located on the long (q) arm of chromosome 17, at band 17q22. Arm ratio per GRCh38 - banding schematic.
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Overview
The RAD51C gene, also known as RAD51 paralog C, is fundamental to the cellular machinery responsible for repairing damaged DNA. This gene's product contributes significantly to maintaining the integrity of the human genome, preventing errors that can lead to disease.
Functioning as part of a larger protein complex, RAD51C is particularly important in homologous recombination, a high-fidelity DNA repair pathway. When this process is compromised due to pathogenic variants in RAD51C, cells become more susceptible to accumulating genetic mutations. This increased genetic instability is directly linked to a heightened risk of developing certain inherited cancers, especially breast and ovarian cancers.
What the gene does
The protein encoded by the RAD51C gene is a member of the RAD51 paralog family, which consists of proteins that are structurally similar to RAD51. These proteins are integral components of the homologous recombination pathway, one of the primary mechanisms eukaryotic cells use to accurately repair double-strand breaks in DNA. Double-strand breaks are particularly dangerous forms of DNA damage as they can lead to significant genomic rearrangements if not properly repaired.
The RAD51C protein works in conjunction with other RAD51 paralogs, including RAD51B, RAD51D, and XRCC3, to facilitate the homologous recombination process. Specifically, it is involved in the earliest stages of this repair pathway, including the recognition of DNA damage and the assembly of the RAD51 filament on single-stranded DNA. This filament is crucial for DNA strand invasion, a key step in recombining homologous sequences to repair the break. The RAD51C protein is also required for effective Holliday junction resolution activity, ensuring the proper completion of the repair process and preventing the formation of potentially harmful DNA structures. Its precise role helps ensure that DNA repair is both efficient and accurate, thereby preserving genetic information.
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Chromosome location
The RAD51C gene is located on chromosome 17, specifically at position 17q22. This chromosomal location indicates that the gene resides on the long (q) arm of chromosome 17, within region 22. The precise mapping helps in understanding its genetic context and how it might be inherited or interact with other genes in the vicinity.
Protein structure
The RAD51C protein has a length of 376 amino acids and contains several functional regions important for its role in DNA repair. A key region, spanning amino acids 1-126, is required for effective Holliday junction resolution activity, demonstrating its involvement in the final steps of homologous recombination. Another notable region, from amino acids 79-136, is crucial for its interaction with other RAD51 paralogs such as RAD51B, RAD51D, and XRCC3, highlighting its role in forming protein complexes essential for DNA repair. Additionally, the protein contains a Nuclear Localisation Signal (NLS) motif at amino acids 366-370, which is responsible for directing the RAD51C protein into the nucleus where DNA repair processes occur.
Key variants
Genetic variants in the RAD51C gene can range from benign changes with no health impact to pathogenic alterations that impair protein function. Pathogenic variants can include point mutations, small insertions or deletions, and larger genomic rearrangements. These alterations can disrupt the normal DNA repair mechanisms, potentially leading to an increased risk for specific types of cancer. The interpretation of a variant's clinical significance relies on various factors, including its location within the gene, its predicted effect on protein function, and its segregation with disease in affected families.
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.407_420del14 | - | Pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1000G>T | p.Glu334Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1004_1005delinsAA | p.Cys335Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1005C>A | p.Cys335Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1018C>T | p.Gln340Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.1026+5_1026+7del | - | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.109del | p.Glu37fs | Pathogenic | ★★☆☆ | Fanconi anemia complementation group O |
c.122del | p.Val41fs | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.133G>T | p.Glu45Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
c.145+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary cancer-predisposing syndrome |
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 RAD51C gene are associated with an increased predisposition to certain types of cancer, primarily inherited breast cancer and ovarian cancer. Individuals carrying these variants have a higher lifetime risk of developing these conditions compared to the general population. The inheritance pattern for these cancer predispositions is autosomal dominant.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic RAD51C variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
RAD51C is a gene with recognised clinical significance within the UK's National Health Service (NHS) Genomic Medicine Service. It is included in several Green-rated panels on PanelApp, indicating that there is strong evidence for its association with human disease. These include the 'Adult solid tumours cancer susceptibility', 'Adult solid tumours for rare disease', 'COVID-19 research', 'DDG2P', ''Familial breast cancer', 'Inherited breast cancer and ovarian cancer' (R208), and 'Inherited ovarian cancer (without breast cancer)' (R207) panels. The gene is also listed in the 'Ovarian cancer pertinent cancer susceptibility' panel.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
Maintaining a healthy lifestyle is a general recommendation for overall wellbeing, and while it does not eliminate genetic risk, it may contribute to a reduced risk of disease in the general population. This includes a balanced diet rich in fruits, vegetables, and whole grains, regular physical activity, and maintaining a healthy weight. Limiting alcohol consumption and avoiding tobacco products are also widely recognised as beneficial for public health. For individuals with a genetic predisposition to cancer, personalised lifestyle advice should be discussed with a healthcare professional.
Supplement considerations
Currently, there is no conclusive scientific evidence to suggest that specific dietary supplements can prevent cancer development in individuals with RAD51C pathogenic variants. Any decision to take supplements should be made in consultation with a healthcare provider, as some supplements can interact with medications or have adverse effects. supplements are not a substitute for medical screening or conventional cancer prevention strategies recommended by healthcare professionals.
Frequently asked questions
What does the RAD51C gene do?
The RAD51C gene provides instructions for making a protein that plays a crucial role in repairing damaged DNA, specifically through a process called homologous recombination. This repair mechanism helps maintain the stability and integrity of the genome.
How are RAD51C variants inherited?
Pathogenic variants in the RAD51C gene are typically inherited in an autosomal dominant pattern. This means that an individual only needs to inherit one copy of the altered gene from either parent to have an increased risk of developing certain cancers.
What types of cancer are associated with RAD51C variants?
Variants in the RAD51C gene are primarily associated with an increased risk of developing inherited breast cancer and ovarian cancer.
If I have a RAD51C variant, does that mean I will definitely get cancer?
No, having a pathogenic RAD51C variant means you have an increased lifetime risk of developing certain cancers compared to the general population. It does not mean you will definitely get cancer, but rather predisposes you to a higher risk.
Where is the RAD51C gene located in the human genome?
The RAD51C gene is located on chromosome 17, specifically at position 17q22. This specifies its exact address on the long arm of chromosome 17.