RAD51

Chr 15

RAD51 recombinase

Also known as: BRCC5, FANCR, HRAD51, HsRad51, HsT16930, MRMV2, RAD51A, RECA

NCBI Gene: 5888 ENSG00000051180 UniProt: Q06609

RAD51 encodes a protein that catalyzes homologous DNA recombination and repair by forming nucleoprotein filaments that facilitate homology search and strand exchange between damaged and template DNA. Mutations cause Fanconi anemia complementation group R, mirror movements, and increased breast cancer susceptibility, with autosomal dominant inheritance. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.644), consistent with its role in DNA repair where complete loss may be tolerated in some contexts.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBreast cancer

UniProtMirror movements 2

UniProtFanconi anemia, complementation group R

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

654

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

LOF*

Mechanism· G2P

📖

GeneReview available — RAD51

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.027

Z-score 2.68

OE 0.33 (0.18–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.62Z-score

OE missense 0.45 (0.38–0.54)

81 obs / 180.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.33 (0.18–0.64)

0≤0.351.4

Missense OE?0.45 (0.38–0.54)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 6 / 18.4Missense obs/exp: 81 / 180.0Syn Z: -0.63

Background carrier burden — how many people carry a rare variant somewhere in RAD51?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

289 rare PASS variants

Rare truncating (LoF)

1 in 4,700

32 rare PASS variants

Rare synonymous (reference)

1 in 350

148 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAD51. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 6,700
South Asian	~43k	1 in 210	1 in 5,600
Remaining (unassigned)	~30k	1 in 180	1 in 3,400
European (Finnish)	~27k	1 in 860	≈ 1 in 13,000
Admixed American	~22k	1 in 180	≈ 1 in 4,500
African / African American	~21k	1 in 140	1 in 460
East Asian	~20k	1 in 210	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 590	none seen
Middle Eastern	~2,884	≈ 1 in 580	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓