RAD50

Chr 5AR

RAD50 double strand break repair protein

ENSG00000113522UniProt: Q92878OMIM: 604040

Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28134932, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:15064416, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (PubMed:11741547, PubMed:9590181, PubMed:9651580, PubMed:9705271). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:11741547, PubMed:12805565, PubMed:28134932). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888)

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.871 OMIM phenotype
Clinical Summary— RAD50
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Gene-Disease Validity (ClinGen)
hereditary breast carcinoma · ADRefuted

Refuted — evidence has disproved this relationship

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
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Some data sources returned errors (1)

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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