MT-CO3

Chr MT

cytochrome c oxidase subunit III

Also known as: COIII, MTCO3

NCBI Gene: 4514 ENSG00000198938 UniProt: P00414 OMIM: 516050

This gene encodes cytochrome c oxidase subunit III, a core component of Complex IV in the mitochondrial respiratory chain that catalyzes the final step of electron transport. Mutations cause Complex IV deficiency presenting as Leigh syndrome, MELAS-like episodes, or recurrent myoglobinuria. Inheritance is maternal through mitochondrial DNA, with clinical severity depending on the degree of heteroplasmy in affected tissues.

GeneReviews OMIM ResearchSummary from Curated mito context

Predicted to enable electron transfer activity. 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, Jun 2026]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy

UniProtMitochondrial complex IV deficiency

UniProtRecurrent myoglobinuria mitochondrial

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — MT-CO3

Authoritative clinical overview · Recommended first read

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Nuclear-gene analyses omitted

MT-CO3 is a mitochondrial protein-coding gene. gnomAD constraint, carrier burden and exome coverage, the ClinVar type breakdown, AlphaFold and transcript-architecture views are built for nuclear genes and are not shown. Population data for mtDNA variants (gnomAD v3.1, homoplasmy and heteroplasmy) is on each variant page.

Where it sits in the mitochondrial genome

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proteinrRNAtRNAouter ring H-strand · inner L-strandMITOMAP confirmedreported (as of 2026-10-07)

37 genes from Ensembl (rCRS numbering, matched to MITOMAP’s Gene Loci); landmarks and disease alleles from MITOMAP (CC BY 3.0). Circular layout after MitoWheel.

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

MITOMAP Disease Variants — MT-CO3

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.9237G>A	V11M	Mitochondrial Respiratory Chain Disorder	Uncertain significance · reported	0
m.9247G>C	S14T	MELAS	Reported	0
m.9266G>T	G20G	Possible association with sepsis	Reported	1
m.9267G>C	A21P	MIDD	Reported	0
m.9331T>C	L42P	Failure to thrive with metabolic acidosis, cognitive impairment, optic atrophy	Reported	1
m.9379G>A	W58Term	MM w lactic acidosis	Uncertain significance · reported	0
m.9387G>A	V61M	Asthenozoospermia	Reported	0
m.9399A>G	S65G	Patient with epilepsy, myopathy, hypoacusis, psychiatric disorders	Reported	1
m.9403C>A	T66K	Possible association with sepsis	Reported	0
m.9415A>G	H70R	Possible association with sepsis	Reported	0
m.9438G>A	G78S	LHON / gout	Conflicting reports	830
m.9444C>T	R80W	Possible LHON helper mutation	Reported	1
m.9478T>C	V91A	Leigh Disease	Uncertain significance · reported	23
m.9480TTTTTCTTCGCAGGA>-	FFFAG-del	Myoglobinuria	Likely pathogenic · confirmed	0
m.9487TCGCAGGATTTTTCT>-	FFAGFF-del	Myoglobinuria	Likely pathogenic	0
m.9490C>T	A95V	Gout	Reported	26
m.9537C>CC	frameshift	Leigh Disease	Likely pathogenic · confirmed	0
m.9544G>A	G113E	Sporadic bilateral optic neuropathy / rhabdomyolysis	Reported	0
m.9553G>A	W116Term	Adult-onset MELAS	Reported	0
m.9559C>-	frameshift	Rhabdomyolysis	Reported	0
m.9660A>C	M152L	LHON	Reported	0
m.9738G>A	A178T	Marfan Syndrome patients	Reported	231
m.9738G>T	A178S	LHON	Reported	0
m.9789T>C	S195P	Myopathy	Reported	0
m.9804G>A	A200T	LHON / MS	Uncertain significance · reported	194
m.9856T>C	I217T	LVNC cardiomyopathy / gout	Reported	21
m.9861T>C	F219L	AD	Reported	141
m.9907G>A	G234D	Cavitating leukodystrophy	Reported	0
m.9921G>A	A239T	Possible LHON helper mutation	Reported	68
m.9952G>A	W249Term	Mitochondrial Encephalopathy	Likely pathogenic · confirmed	0
m.9957T>C	F251L	PEM / MELAS / NAION / HCM / gout	Reported	53
m.9966G>A	V254I	LHON possible helper variant	Reported	451
m.9972A>C	I256L	EXIT & APS2 - possible link	Reported	2
m.9984G>A	G260Term	Suspected mito disease	Reported	0