MRE11

Chr 11AR

MRE11 double strand break repair nuclease

Also known as: ATLD, HNGS1, MRE11A, MRE11B

NCBI Gene: 4361ENSG00000020922UniProt: P49959

This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Ataxia-telangiectasia-like disorder 1MIM #604391
AR
519
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— MRE11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 329 VUS of 519 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.84LOEUF
pLI 0.000
Z-score 2.40
OE 0.60 (0.44–0.84)
Tolerant

Typical tolerance to LoF variation

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 (0.90–1.07)
378 obs / 385.2 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.0.60 (0.44–0.84)
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 (0.90–1.07)
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.1.11
0≤1.21.6
LoF obs/exp: 26 / 43.0Missense obs/exp: 378 / 385.2Syn Z: -0.97

ClinVar Variant Classifications

519 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic21
VUS329
Likely Benign132
Benign5
Conflicting14
18
Pathogenic
21
Likely Pathogenic
329
VUS
132
Likely Benign
5
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
16
0
18
Likely Pathogenic
14
2
5
0
21
VUS
0
308
19
2
329
Likely Benign
0
7
16
109
132
Benign
0
1
3
1
5
Conflicting
—14
Total1631859112519

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

View in ClinVar →

Protein Context — Lollipop Plot

MRE11 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MRE11-related ataxia telangiectasia-like disorder

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ataxia-telangiectasia-like disorder 1

MIM #604391

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.
Huang RX et al.·Signal Transduct Target Ther
2020Review
Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2.
Samuel D et al.·Cells
2022Review
Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta-analysis.
Stastna B et al.·Int J Cancer
2024Meta-analysis
MRE11 UFMylation promotes ATM activation.
Wang Z et al.·Nucleic Acids Res
2019
NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.
Belhadj S et al.·Clin Cancer Res
2023
NBS1 facilitates preribosomal RNA biogenesis.
Luo M et al.·Proc Natl Acad Sci U S A
2025
Targeting MTAP increases PARP inhibitor susceptibility in triple-negative breast cancer through a feed-forward loop.
Zeng X et al.·J Clin Invest
2025
Cell stretching activates an ATM mechano-transduction pathway that remodels cytoskeleton and chromatin.
Bastianello G et al.·Cell Rep
2023Functional
MRNIP condensates promote DNA double-strand break sensing and end resection.
Wang YL et al.·Nat Commun
2022
Saikosaponin D Mitigates Radioresistance in Triple-Negative Breast Cancer by Inducing MRE11 De-Lactylation via HIF1α/HDAC5 Pathway.
Li J et al.·Theranostics
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
DNA polymerase kappa stabilized by Ptbp2 interacts with MRE11 and promotes genomic instability in leukemia.
Lama S et al.·Cell Death Discov
2026🔓 Open Access
MRE11 deacetylation by SIRT2 promotes DNA binding to facilitate DNA end resection and ATM-dependent signaling.
Sesay F et al.·J Clin Invest
2026🔓 Open Access
Molecular characterisation of Toxoplasma gondii Mre11 reveals unique structural features and potential as a therapeutic target.
Ruiz DM et al.·Sci Rep
2025🔓 Open Access
Mutual, spatially limited control of meiotic DNA break formation by Mre11-Rad50-Nbs1 DNA repair complex and Tel1 (ATM) protein kinase.
Hyppa RW et al.·Nucleic Acids Res
2025🔓 Open Access
Differential expression of a disease-associated MRE11 variant reveals distinct phenotypic outcomes.
DeFoer MB et al.·Hum Mol Genet
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
Prostate Cancer Metastatic Castration-ResistantAbnormal DNA RepairMetastatic Prostate Carcinoma

Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

ACTIVE NOT RECRUITING
NCT03012321Phase PHASE2Northwestern UniversityStarted 2017-01-12
OlaparibAbiraterone AcetatePrednisone
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

External Resources

Links to major genomics databases and tools