RAD51C
Chr 17ARRAD51 paralog C
Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD51 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis
Primary Disease Associations & Inheritance
Definitive β sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 β loss-of-function & missense intolerance
Highly tolerant β LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
594 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar Β· 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 53 | 0 | 32 | 0 | 85 |
Likely Pathogenic | 20 | 3 | 13 | 0 | 36 |
VUS | 4 | 149 | 43 | 5 | 201 |
Likely Benign | 0 | 10 | 114 | 73 | 197 |
Benign | 0 | 19 | 8 | 22 | 49 |
Conflicting | β | 26 | |||
| Total | 77 | 181 | 210 | 100 | 594 |
LoF = frameshift, stop gained/lost, canonical splice Β· Counts from ClinVar esearch Β· Updated hourly
View in ClinVar βProtein Context β Lollipop Plot
RAD51C Β· protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
Gene2Phenotype curations Β· DECIPHER consortium patient cohort (public variants) Β· deciphergenomics.org
OMIM β Genotype-Phenotype Relationships
1 OMIM entry
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A PARG Inhibitor DAT-2645 Monotherapy in Patients with Advanced/Metastatic Solid Tumors Harboring BRCA1/2 Loss of Function Alterations And/or Other Defects in the DDR Pathway
NOT YET RECRUITINGStudy of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations
RECRUITINGSurgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
ACTIVE NOT RECRUITINGEvaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction: the PROVE Study
RECRUITINGA Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors
RECRUITINGAn Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results
RECRUITINGPHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer
RECRUITINGTUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention
RECRUITINGNiraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects
ACTIVE NOT RECRUITINGRisk-reducing Strategies, Including Fimbriectomy, in Women With a Germline Mutation Predisposing to Ovarian or Pelvic Cancer
NOT YET RECRUITINGAscending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents
ACTIVE NOT RECRUITINGSerial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer
RECRUITINGExternal Resources
Links to major genomics databases and tools