MT-CO2

Chr MT

cytochrome c oxidase subunit II

Also known as: COII, MTCO2

NCBI Gene: 4513 ENSG00000198712 UniProt: P00403

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.

GeneReviews ResearchSummary from Curated mito context

Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— MT-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

10 unique Pathogenic / Likely Pathogenic· 57 VUS of 130 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MT-CO2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

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

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic5

VUS57

Likely Benign33

Benign29

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

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

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	—	—	—	—	5
Likely Pathogenic	—	—	—	—	5
VUS	—	—	—	—	57
Likely Benign	—	—	—	—	33
Benign	—	—	—	—	29
Total	—				129

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap MT-CO2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

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.

MITOMAP Disease Variants — MT-CO2

MITOMAP ↗

Variant	AA	Disease	Status	GenBank
m.7587T>C	M1T	Mitochondrial Encephalomyopathy	Cfrm [LP]	0.000%
m.7598G>A	A5T	Possible LHON helper variant	Reported	104.920%
m.7623C>T	T13I	LHON	Reported	0.000%
m.7630T>-	frameshift	MELAS	Reported	0.000%
m.7637G>A	E18K	PD risk factor / neurological impairment	Reported [VUS]	0.310%
m.7671T>A	M29K	MM	Reported [VUS]	0.000%
m.7695T>C	L37P	Cerebellar and pyramidal syndrome with cognitive impairment	Reported	0.000%
m.7697G>A	V38I	Possible HCM susceptibility, high altitude adaptation	Reported	48.100%
m.7706G>A	A41T	Alpers-Huttenlocher-like	Reported	1.680%
m.7749T>C	I55T	Possible association with sepsis	Reported	0.310%
m.7859G>A	D92N	Progressive Encephalomyopathy	Reported	28.640%
m.7868C>T	L95F	LHON	Reported - possibly synergistic	2.140%
m.7877A>C	K98Q	PEG glaucoma	Reported	0.000%
m.7887G>A	G101D	Cerebellar ataxia + neuropathy + exercise intolerance	Reported	0.000%
m.7896G>A	W104Term	Multisystem Disorder	Cfrm [P]	0.000%
m.7943T>C	S120P	Possible association with sepsis	Reported	0.000%
m.7965T>C	F127S	Hepatic failure / COX deficiency	Reported	0.150%
m.7970G>T	E129Term	Encephalopathy	Reported	0.000%
m.7989T>C	L135P	Rhabdomyolysis	Reported [VUS]	0.000%
m.8010T>C	V142A	Developmental delay, ataxia, seizure, hypotonia, lactic acidosis	Reported	0.610%
m.8021A>G	I146V	Asthenozoospermia	Reported	0.610%
m.8024G>A	E147K	Bioenergetic deficiency with optic atrophy	Reported	0.150%
m.8042AT>-	frameshift	Lactic Acidosis	Reported [VUS]	0.000%
m.8078G>A	V165I	DEAF	Reported	4.290%
m.8088T>-	frameshift	Mitochondrial myopathy with complex IV deficiency	Cfrm [LP]	0.000%
m.8108A>G	I175V	SNHL	Reported	12.100%
m.8119T>-	frameshift	Biliary atresia	Reported	0.000%
m.8156G>-	frameshift	Multi-system mitochondrial disorder	Reported	0.000%
m.8163A>G	Y193C	Late-onset cerebellar ataxia	Reported	0.000%
m.8231C>A	L216M	Coronary artery disease risk factor	Reported	0.000%
m.8241T>G	F219C	MIDD+retinopathy	Conflicting reports	0.000%
m.8249G>A	G222Term	Mitochondrial myopathy	Reported	0.000%