MRE11

Chr 11AR

MRE11 double strand break repair nuclease

Also known as: ATLD, HNGS1, MRE11A, MRE11B

This gene encodes MRE11, a nuclease that forms the MRN complex essential for DNA double-strand break repair, homologous recombination, and telomere maintenance. Mutations cause ataxia-telangiectasia-like disorder 1, an autosomal recessive condition characterized by progressive ataxia and telangiectasias affecting the nervous system and vasculature. The gene is highly constrained against loss-of-function variants (pLI near 1.0), indicating that complete loss of function is likely incompatible with normal development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.841 OMIM phenotype
Clinical SummaryMRE11
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Gene-Disease Validity (ClinGen)
hereditary breast carcinoma · ADRefuted

Refuted — evidence has disproved this relationship

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 312 VUS of 500 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — MRE11
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.40
OE 0.60 (0.440.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.98 (0.901.07)
378 obs / 385.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.440.84)
00.351.4
Missense OE0.98 (0.901.07)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 26 / 43.0Missense obs/exp: 378 / 385.2Syn Z: -0.97
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMRE11-related ataxia telangiectasia-like disorderLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6744th %ile
GOF
0.3590th %ile
LOF
0.4331th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic20
VUS312
Likely Benign123
Conflicting5
14
Pathogenic
20
Likely Pathogenic
312
VUS
123
Likely Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
6
0
14
Likely Pathogenic
18
0
2
0
20
VUS
0
297
12
3
312
Likely Benign
0
3
21
99
123
Benign
0
0
0
0
0
Conflicting
5
Total2630041102474

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗