MTO1

Chr 6AR

mitochondrial tRNA translation optimization 1

Also known as: CGI-02, COXPD10

NCBI Gene: 25821ENSG00000135297UniProt: Q9Y2Z2

This gene encodes a mitochondrial protein thought to be involved in mitochondrial tRNA modification. The encoded protein may also play a role in the expression of the non-syndromic and aminoglycoside-induced deafness phenotypes associated with a specific mutation in the mitochondrial 12S rRNA gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 10MIM #614702
AR
100
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MTO1
🧬
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
10 Pathogenic / Likely Pathogenic· 85 VUS of 100 total submissions

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.
0.64LOEUF
pLI 0.000
Z-score 3.25
OE 0.42 (0.28–0.64)
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.
0.65Z-score
OE missense 0.91 (0.83–0.99)
373 obs / 410.0 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.0.42 (0.28–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.83–0.99)
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.0.94
0≤1.21.6
LoF obs/exp: 15 / 36.1Missense obs/exp: 373 / 410.0Syn Z: 0.54

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS85
Likely Benign3
Conflicting2
8
Pathogenic
2
Likely Pathogenic
85
VUS
3
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
6
0
8
Likely Pathogenic
1
0
1
0
2
VUS
2
74
9
0
85
Likely Benign
0
1
0
2
3
Benign
0
0
0
0
0
Conflicting
—2
Total575162100

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

View in ClinVar →

Protein Context — Lollipop Plot

MTO1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MTO1-related infantile hypertrophic cardiomyopathy and lactic acidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 10

MIM #614702

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MTO1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and genetic analysis of combined oxidative phosphorylation defificiency-10 caused by MTO1 mutation.
Zhou C et al.·Clin Chim Acta
2022
Taurine hypomodification underlies mitochondrial tRNATrp-related genetic diseases.
Lu JL et al.·Nucleic Acids Res
2024
MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy.
Becker L et al.·PLoS One
2014Functional
Circular RNA circ-MTO1 serves as a novel potential diagnostic and prognostic biomarker for gallbladder cancer.
Wang X et al.·Eur Rev Med Pharmacol Sci
2020
Modern genomic techniques in the identification of genetic causes of cardiomyopathy.
Spracklen TF et al.·Heart
2022Review
Circular RNA MTO1 intercorrelates with microRNA-630, both associate with Enneking stage and/or pathological fracture as well as prognosis in osteosarcoma patients.
Shi Z et al.·J Clin Lab Anal
2021Cohort
The genotypic and phenotypic spectrum of MTO1 deficiency.
O'Byrne JJ et al.·Mol Genet Metab
2018Case report
Clinical, Genetic, and Histological Characterization of Patients with Rare Neuromuscular and Mitochondrial Diseases Presenting with Different Cardiomyopathy Phenotypes.
Monda E et al.·Int J Mol Sci
2023Cohort
Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis.
Ghezzi D et al.·Am J Hum Genet
2012
MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.
Baruffini E et al.·Hum Mutat
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools