RAD51
Chr 15ADSomaticRAD51 recombinase
Also known as: BRCC5, FANCR, HRAD51, HsRad51, HsT16930, MRMV2, RAD51A, RECA
The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
References
ClinVar Variant Classifications
505 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 3 | 0 | 0 | 5 |
Likely Pathogenic | 2 | 7 | 0 | 0 | 9 |
VUS | 6 | 236 | 3 | 2 | 247 |
Likely Benign | 2 | 16 | 36 | 143 | 197 |
Benign | 0 | 2 | 26 | 0 | 28 |
Conflicting | — | 7 | |||
| Total | 12 | 264 | 65 | 145 | 493 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →6 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap RAD51 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
RAD51 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase II Clinical Trial Evaluating the Combination of Olaparib and Temozolomide for the Treatment of Advanced Uterine Leiomyosarcoma
ACTIVE NOT RECRUITINGA Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy
ACTIVE NOT RECRUITINGOlaparib In Metastatic Breast Cancer
ACTIVE NOT RECRUITINGNordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC
ACTIVE NOT RECRUITINGAbiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects
ACTIVE NOT RECRUITINGMeasuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
RECRUITINGStudying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes
RECRUITINGPancreatic Cancer Genetics
RECRUITINGMicrodevice In Ovarian, Fallopian Tube, And Peritoneal Cancer
RECRUITINGTesting the Addition of an Anti-cancer Drug, Elimusertib (BAY 1895344) ATR Inhibitor, to the Chemotherapy Treatment (Gemcitabine) for Advanced Pancreatic and Ovarian Cancer, and Advanced Solid Tumors
ACTIVE NOT RECRUITINGTesting How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers
RECRUITINGOlaparib and Durvalumab (MEDI4736) in Patients with Metastatic Pancreatic Cancer and DNA Damage Repair Genes Alterations
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools