RAD50

Chr 5

RAD50 double strand break repair protein

Also known as: NBSLD, RAD502, hRad50

NCBI Gene: 10111ENSG00000113522UniProt: Q92878

The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNijmegen breakage syndrome-like disorder

Clinical highlights

Gene-disease validity (ClinGen)
hereditary breast carcinoma · ADRefutedevidence has disproved this relationship2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
132
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.87
LOEUF
LOF
Mechanism· G2P
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GeneReview available — RAD50
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?
0.87LOEUF
pLI 0.000
Z-score 2.48
OE 0.70 (0.56–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.25Z-score
OE missense 0.86 (0.81–0.93)
587 obs / 678.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.70 (0.56–0.87)
0≤0.351.4
Missense OE?0.86 (0.81–0.93)
0≤0.61.4
Synonymous OE?1.07
0≤1.21.6
LoF obs/exp: 54 / 77.6Missense obs/exp: 587 / 678.6Syn Z: -0.86

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RAD50 · 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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients