RAD51D

Chr 17

RAD51 paralog D

Also known as: BROVCA4, R51H3, RAD51L3, TRAD

NCBI Gene: 5892 ENSG00000185379 UniProt: O75771

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, which are known to be involved in the homologous recombination and repair of DNA. This protein forms a complex with several other members of the RAD51 family, including RAD51L1, RAD51L2, and XRCC2. The protein complex formed with this protein has been shown to catalyze homologous pairing between single- and double-stranded DNA, and is thought to play a role in the early stage of recombinational repair of DNA. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream ring finger and FYVE-like domain containing 1 (RFFL) gene. [provided by RefSeq, Jan 2011]

Primary Disease Associations & Inheritance

{Breast-ovarian cancer, familial, susceptibility to, 4}MIM #614291

Active trials

Pathogenic / LP

600

ClinVar variants

Pubs (1 yr)

-0.1

Missense Z

1.22

LOEUF

Clinical Summary— RAD51D

🧬

Gene-Disease Validity (ClinGen)

RAD51D-related cancer predisposition · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

90 Pathogenic / Likely Pathogenic· 237 VUS of 600 total submissions

💊

Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

📖

GeneReview available — RAD51D

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — 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 — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.22LOEUF

pLI 0.000

Z-score 0.82

OE 0.80 (0.54–1.22)

Tolerant

Highly tolerant — 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.

-0.11Z-score

OE missense 1.02 (0.91–1.15)

198 obs / 193.6 exp

Tolerant

Tolerant to missense variation

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.0.80 (0.54–1.22)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.91–1.15)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01

0≤1.21.6

LoF obs/exp: 16 / 20.0Missense obs/exp: 198 / 193.6Syn Z: -0.04

0.74top 25%

GOF

0.5268th %ile

LOF

0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55

Likely Pathogenic35

VUS237

Likely Benign215

Benign43

Conflicting15

Pathogenic

Likely Pathogenic

237

VUS

215

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	32	0	23	0	55
Likely Pathogenic	32	0	3	0	35
VUS	12	189	28	8	237
Likely Benign	0	2	121	92	215
Benign	0	0	4	39	43
Conflicting	—				15
Total	76	191	179	139	600

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

View in ClinVar →

Protein Context — Lollipop Plot

RAD51D · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RAD51D related cancer

definitive

ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure

Cancer

G2P ↗

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

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GeneReview available — RAD51D

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

Metastatic Pancreatic Cancer

Olaparib and Durvalumab (MEDI4736) in Patients with Metastatic Pancreatic Cancer and DNA Damage Repair Genes Alterations

ACTIVE NOT RECRUITING

NCT05659914Phase PHASE2Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)Started 2022-11-28

olaparib+durvalumab

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

Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING

NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21

NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

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

Malignant Neoplasm of BreastBreast Cancer

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO

ACTIVE NOT RECRUITING

NCT05033756Phase PHASE2Institut fuer FrauengesundheitStarted 2022-07-30

Pembrolizumab Injection [Keytruda]Olaparib Oral Tablet [Lynparza]

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

Breast CancerTriple Negative Breast Neoplasms

NordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC

ACTIVE NOT RECRUITING

NCT04335669Phase PHASE3Lund University HospitalStarted 2019-12-20

epirubicin, cyclophosphamide, paclitaxel, carboplatin, pembrolizumabepirubicin, cyclophosphamide, capecitabine, paclitaxel, carboplatin, pembrolizumab

Advanced Malignant Solid NeoplasmAnn Arbor Stage III Non-Hodgkin LymphomaAnn Arbor Stage IV Non-Hodgkin Lymphoma

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

ACTIVE NOT RECRUITING

NCT03155620Phase PHASE2National Cancer Institute (NCI)Started 2017-07-31

Biopsy ProcedureBiospecimen CollectionBone Marrow Aspiration and Biopsy

BRCA MutationPALB2 Gene MutationDuctal Carcinoma in Situ

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion

ACTIVE NOT RECRUITING

NCT06033092Phase PHASE2European Institute of OncologyStarted 2024-06-21

Tamoxifen 10 mg TabletIntermittent caloric restrictionStep counter Device

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

Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING

NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01

ST-01156

Clinical Literature

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3