MGME1

Chr 20AR

mitochondrial genome maintenance exonuclease 1

Also known as: C20orf72, DDK1, MTDPS11, bA504H3.4

NCBI Gene: 92667ENSG00000125871UniProt: Q9BQP7

The protein is a nuclear-encoded mitochondrial RecB-type exonuclease that cleaves single-stranded DNA and is necessary for maintaining mitochondrial genome synthesis. Mutations cause mitochondrial DNA depletion syndrome-11, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects disrupting mitochondrial DNA maintenance.

Summary from RefSeq, OMIM, UniProt, Mechanism
Research Assistant →

Primary Disease Associations & Inheritance

Mitochondrial DNA depletion syndrome 11MIM #615084
AR
0
Active trials
8
Pubs (1 yr)
39
P/LP submissions
3%
P/LP missense
0.84
LOEUF
DN
Mechanism· predicted
Clinical Summary— MGME1
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 102 VUS of 227 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.002
Z-score 2.03
OE 0.45 (0.25–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.26Z-score
OE missense 1.05 (0.94–1.19)
187 obs / 177.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.45 (0.25–0.84)
0≤0.351.4
Missense OE1.05 (0.94–1.19)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 7 / 15.6Missense obs/exp: 187 / 177.3Syn Z: 0.67
DN
0.6938th %ile
GOF
0.4480th %ile
LOF
0.3260th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

227 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic2
VUS102
Likely Benign67
Benign13
Conflicting4
34
Pathogenic
2
Likely Pathogenic
102
VUS
67
Likely Benign
13
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
28
0
34
Likely Pathogenic
0
0
2
0
2
VUS
3
92
7
0
102
Likely Benign
0
9
23
35
67
Benign
0
2
9
2
13
Conflicting
—4
Total81046937222

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

View in ClinVar →

Protein Context — Lollipop Plot

MGME1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
MGME1 associates with poor prognosis and is vital for cell proliferation in lower-grade glioma
Xiao F et al.·Aging (Albany NY)
2023
The 5'-phosphate enhances the DNA-binding and exonuclease activities of human mitochondrial genome maintenance exonuclease 1 (MGME1)
Urrutia KM et al.·J Biol Chem
2022
Mice lacking the mitochondrial exonuclease MGME1 develop inflammatory kidney disease with glomerular dysfunction
Milenkovic D et al.·PLoS Genet
2022
Integrative multi-omics analysis unveils the connection between transcriptomic characteristics associated with mitochondria and the tumor immune microenvironment in lower-grade gliomas
Jiang C et al.·Sci Rep
2024
Nuclease-induced stepwise photodropping (NISP) to precisely investigate single-stranded DNA degradation behaviors of exonucleases and endonucleases
Chiu HP et al.·Nucleic Acids Res
2024
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Homozygous MGME1 Variant in Turkish Siblings: First Reported Case With Successful Heart Transplantation, Expanding the Clinical Spectrum of MGME1-Related Mitochondrial Disease.
Acikgoz NB et al.·Am J Med Genet A
2026
Unspliced XBP1 enhences metabolic reprogramming in colorectal cancer cells by interfering with the mitochondrial localization of MGME1.
Zhang J et al.·Biochem Biophys Res Commun
2025
Identification of HIBCH and MGME1 as Mitochondrial Dynamics-Related Biomarkers in Alzheimer's Disease Via Integrated Bioinformatics Analysis.
Li H et al.·IET Syst Biol
2025Open Access
Structural basis of how MGME1 processes DNA 5' ends to maintain mitochondrial genome integrity.
Mao EYC et al.·Nucleic Acids Res
2024Open Access
Absence of both MGME1 and POLG EXO abolishes mtDNA whereas absence of either creates unique mtDNA duplications.
Gonzalez CD et al.·J Biol Chem
2024Open Access
Top 5 resultsSearch Europe PMC ↗

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