MT-CO2

Chr MT

cytochrome c oxidase subunit II

Also known as: COII, MTCO2

This gene encodes cytochrome c oxidase subunit II, a core component of Complex IV of the mitochondrial respiratory chain that catalyzes the final step of electron transport and oxygen consumption. Mutations cause Complex IV deficiency presenting as encephalomyopathy with variable neurological manifestations including developmental delay, seizures, and progressive neurodegeneration. Inheritance is maternal through the mitochondrial genome, with clinical severity often correlating with the degree of heteroplasmy.

Summary from Curated mito context
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Primary Disease Associations & Inheritance

UniProtMitochondrial complex IV deficiency
0
Active trials
24
Pubs (1 yr)
53
P/LP submissions
P/LP missense
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryMT-CO2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · MTLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 57 VUS of 138 total submissions
📖
GeneReview available — MT-CO2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

Constraint data not available from gnomAD.

DN
0.80top 10%
GOF
0.82top 10%
LOF
0.07100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

138 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic8
VUS57
Likely Benign33
Benign29
10
Pathogenic
8
Likely Pathogenic
57
VUS
33
Likely Benign
29
Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
Likely Pathogenic
8
VUS
57
Likely Benign
33
Benign
29
Total137

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MT-CO2 · 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

No active trials found for this gene.

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Clinical Literature
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