MT-CO3

Chr MTAR

cytochrome c oxidase subunit III

Also known as: COIII, MTCO3

NCBI Gene: 4514ENSG00000198938UniProt: P00414

Predicted to contribute to cytochrome-c oxidase activity. Involved in respiratory chain complex IV assembly. Located in mitochondrial membrane. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2025]

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 24MIM #621431
AR
Mitochondrial complex IV deficiency, nuclear type 24MIM #621431
AR
UniProtLeber hereditary optic neuropathy
UniProtRecurrent myoglobinuria mitochondrial
186
ClinVar variants
25
Pathogenic / LP
—
pLI score
0
Active trials
Clinical Summary— MT-CO3
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · MTLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 82 VUS of 186 total submissions

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic7
VUS82
Likely Benign39
Benign39
Conflicting1
18
Pathogenic
7
Likely Pathogenic
82
VUS
39
Likely Benign
39
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————18
Likely Pathogenic
————7
VUS
————82
Likely Benign
————39
Benign
————39
Conflicting
—1
Total—186

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MT-CO3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

3 OMIM entries

OMIM

Mitochondrial complex IV deficiency, nuclear type 24

MIM #621431

Molecular basis of disorder known

Autosomal recessive

Mitochondrial complex IV deficiency, nuclear type 24

MIM #621431

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MT-CO3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
Tostes K et al.·Autophagy
2022
Rhabdomyolysis due to mtDNA pathogenic variants: Report of a subject with a novel MT-CO3 variant and review of the literature.
Barca E et al.·Mol Genet Metab
2026Review
Analysis of Inherited Optic Neuropathies.
Lazdinyte S et al.·Klin Monbl Augenheilkd
2019
Inherited and de novo variants in young females potentially associated with pelvic organ prolapse.
Sadakierska-Chudy A et al.·Am J Obstet Gynecol
2025
A novel nonsense variant in MT-CO3 causes MELAS syndrome.
Wang W et al.·Neuromuscul Disord
2021Case report
Next-generation sequencing profiling of mitochondrial genomes in gout.
Tseng CC et al.·Arthritis Res Ther
2018
Next-generation sequencing of the whole mitochondrial genome identifies functionally deleterious mutations in patients with multiple sclerosis.
Al-Kafaji G et al.·PLoS One
2022Cohort
Clinical and molecular characterization of pediatric mitochondrial disorders in south of China.
Hu C et al.·Eur J Med Genet
2020
Novel non-neutral mitochondrial DNA mutations found in childhood acute lymphoblastic leukemia.
Järviaho T et al.·Clin Genet
2018
Mitochondrial variants in MT-CO2 and D-loop instability are involved in MUTYH-associated polyposis.
Errichiello E et al.·J Mol Med (Berl)
2015
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