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

{Breast-ovarian cancer, familial, susceptibility to, 3}MIM #613399
Fanconi anemia, complementation group OMIM #613390
AR
UniProtFanconi anemia complementation group O
594
ClinVar variants
121
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summaryβ€” RAD51C
🧬
Gene-Disease Validity (ClinGen)
RAD51C-related cancer predisposition Β· ADDefinitive

Definitive β€” sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚑
Population Constraint (gnomAD)
Low constraint (pLI 0.00) β€” loss-of-function variants are relatively tolerated in the population.
πŸ“‹
ClinVar Variants
121 Pathogenic / Likely PathogenicΒ· 201 VUS of 594 total submissions
πŸ’Š
Clinical Trials
12 active or recruiting trials β€” potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 β€” loss-of-function & missense intolerance

Tolerant β€” LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE β€” the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.49LOEUF
pLI 0.000
Z-score -0.11
OE 1.03 (0.72–1.49)
Tolerant

Highly tolerant β€” LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.13Z-score
OE missense 0.98 (0.87–1.10)
200 obs / 205.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≀ 0.35 = strong LoF constraint signal.1.03 (0.72–1.49)
0≀0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≀ 0.6 = fewer missense variants than expected by chance.0.98 (0.87–1.10)
0≀0.61.4
Synonymous OE?Control metric β€” synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≀1.21.6
LoF obs/exp: 20 / 19.5Missense obs/exp: 200 / 205.1Syn Z: 0.18

ClinVar Variant Classifications

594 submitted variants in ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic36
VUS201
Likely Benign197
Benign49
Conflicting26
85
Pathogenic
36
Likely Pathogenic
201
VUS
197
Likely Benign
49
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar Β· 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
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
Total77181210100594

LoF = frameshift, stop gained/lost, canonical splice Β· Counts from ClinVar esearch Β· Updated hourly

View in ClinVar β†’

Protein 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

RAD51C-related Fanconi anemia

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P β†—
missense variantinframe deletioninframe insertion

RAD51C-related cancer

definitive
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Cancer
G2P β†—

Gene2Phenotype curations Β· DECIPHER consortium patient cohort (public variants) Β· deciphergenomics.org

OMIM β€” Genotype-Phenotype Relationships

1 OMIM entry

RAD51 PARALOG C; RAD51C
MIM #602774 Β· *

{Breast-ovarian cancer, familial, susceptibility to, 3}

MIM #613399

Molecular basis of disorder known

Fanconi anemia, complementation group O

MIM #613390

Molecular basis of disorder known

Autosomal recessive
πŸ“–
GeneReview available β€” RAD51C
Authoritative clinical overview Β· NCBI Bookshelf Β· Recommended first read
Open GeneReview β†—
Clinical Literature
Landmark / reviewRecent case evidence

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Solid CancersBRCA MutationHRD Cancer

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 RECRUITING
NCT06614751Phase PHASE1Danatlas Pharmaceuticals Co., LtdStarted 2024-11-01
DAT-2645 tabletDAT-2645 tablet
Renal Cell CarcinomaMetastatic Renal Cell CarcinomaKidney Cancer

Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations

RECRUITING
NCT03786796Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2019-06-03
Olaparib
Deleterious BARD1 Gene MutationDeleterious BRCA1 Gene MutationDeleterious BRCA2 Gene Mutation

Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations

ACTIVE NOT RECRUITING
NCT02760849Phase NAM.D. Anderson Cancer CenterStarted 2016-05-02
Laboratory Biomarker AnalysisOophorectomyQuality-of-Life Assessment
Ovarian Cancer

Evaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction: the PROVE Study

RECRUITING
NCT06935344Catholic University of the Sacred HeartStarted 2025-06-01
Polygenic Risk ScoreBiopsy on normal contralateral ovaryPharmacogenetic profiles
Advanced or Metastatic Solid TumorsBreast CancerOvarian Cancer

A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors

RECRUITING
NCT05787587Phase PHASE1IDEAYA BiosciencesStarted 2023-04-18
IDE-161Pembrolizumab
BRCA1 MutationPOLD1 Gene MutationCDKN2A Mutation

An 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

RECRUITING
NCT05420064Phase NAMemorial Sloan Kettering Cancer CenterStarted 2022-12-01
Intervention Arm At-risk Relative/ARR ContactsMyGene PortalStandard of Care
Breast NeoplasmTriple Negative Breast Cancer (TNBC)HRD

PHOENIX 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

RECRUITING
NCT03740893Phase PHASE2Institute of Cancer Research, United KingdomStarted 2019-10-15
AZD6738OlaparibDurvalumab
BRCA1 Gene MutationBRCA2 Gene MutationRAD51C Gene Mutation

TUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention

RECRUITING
NCT04294927Phase NAUniversity Medical Center NijmegenStarted 2020-03-01
Risk-reducing salpingectomy with delayed oophorectomyRisk-reducing salpingo-oophorectomy
ATM Gene MutationBRCA1 Gene MutationBRCA2 Gene Mutation

Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects

ACTIVE NOT RECRUITING
NCT04030559Phase PHASE2Marc Dall'Era, MDStarted 2020-02-25
NiraparibNiraparib Tosylate MonohydrateRadical Prostatectomy
Tubo-ovarian CarcinomaHigh-grade Serous CarcinomaPrimary Peritoneal Carcinoma Stage III

Risk-reducing Strategies, Including Fimbriectomy, in Women With a Germline Mutation Predisposing to Ovarian or Pelvic Cancer

NOT YET RECRUITING
NCT06726330Phase NACentre Oscar LambretStarted 2025-03
Fimbriectomy Followed by Delayed Oophorectomy (F-DO)Bilateral Salpingo-Oophorectomy
Adv Solid Malig - H&N SCC, ATM Pro / Def NSCLC, Gastric, Breast and Ovarian Cancer

Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents

ACTIVE NOT RECRUITING
NCT02264678Phase PHASE1, PHASE2AstraZenecaStarted 2014-10-31
Administration of ceralasertibAdministration of ceralasertib in combination with olaparibAdministation of ceralasertib in combination with durvalumab
Triple Negative Breast CancerBreast Cancer

Serial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer

RECRUITING
NCT04768426Phase PHASE2Stanford UniversityStarted 2021-02-03
Capecitabine