MT-CO1

Chr MT

cytochrome c oxidase subunit I

Also known as: COI, MTCO1

NCBI Gene: 4512 ENSG00000198804 UniProt: P00395 OMIM: 516030

Cytochrome c oxidase subunit I is the catalytic core of Complex IV in the mitochondrial respiratory chain, responsible for the final step of electron transport and oxygen reduction during oxidative phosphorylation. Mutations cause Complex IV deficiency presenting with variable manifestations including sideroblastic anemia and recurrent myoglobinuria, with clinical severity depending on the degree of heteroplasmy in affected tissues. Inheritance is maternal through mitochondrial DNA.

GeneReviews OMIM ResearchSummary from Curated mito context

Contributes to cytochrome-c oxidase activity. Predicted to be involved in aerobic respiration; positive regulation of vasoconstriction; and respiratory electron transport chain. Located in mitochondrial membrane. Part of respiratory chain complex IV. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy

UniProtMitochondrial complex IV deficiency

UniProtRecurrent myoglobinuria mitochondrial

UniProtDeafness, sensorineural, 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

—

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — MT-CO1

Authoritative clinical overview · Recommended first read

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Nuclear-gene analyses omitted

MT-CO1 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-CO1 · protein map & ClinVar variants

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

MITOMAP Disease Variants — MT-CO1

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.5906G>A	M1M	MELAS/Leigh overlap Syndrome	Reported	0
m.5911C>T	A3V	Prostate Cancer / PCOS patient	Reported	299
m.5913G>A	D4N	Prostate Cancer / hypertension	Reported	560
m.5920G>A	W6Term	Myoglobinuria / EXIT	Likely pathogenic · confirmed	0
m.5935A>G	N11S	Prostate Cancer	Reported	1
m.5973G>A	A24T	Prostate Cancer	Reported	16
m.6020C>A	A39A	Possible association with sepsis	Reported	0
m.6020CGAGC>-	AELGQ-AGPATerm	Motor Neuron Disease	Reported	0
m.6081G>A	A60T	Prostate Cancer	Reported	1
m.6145G>A	W81Term	Unspecified suspected mitochondrial disorder	Uncertain significance · reported	0
m.6150G>A	V83I	Prostate Cancer / POAG (primary open-angle glaucoma) risk factor	Reported	292
m.6253T>C	M117T	Prostate Cancer / enriched in POAG cohort / PCOS patient	Reported	660
m.6261G>A	A120T	Prostate Cancer / LHON	Reported	531
m.6267G>A	A122T	Prostate Cancer	Reported	109
m.6285G>A	V128I	Prostate Cancer	Reported	136
m.6307A>G	N135S	Asthenozoospermic infertility	Reported	3
m.6328C>T	S142F	EXIT (Exercise Intolerance)	Uncertain significance · reported	0
m.6340C>T	T146I	Prostate Cancer	Reported	111
m.6367T>C	V155A	Possible association with sepsis	Reported	24
m.6459T>C	W186R	Sepsis susceptibility	Reported	0
m.6474A>G	T191A	Maternally inherited childhood epilepsy and ataxia	Reported	0
m.6480G>A	V193I	Prostate Cancer / enriched in POAG cohort	Reported	175
m.6489C>A	L196I	CO1 deficiency with epilepsia partialis continua	Reported	90
m.6526T>C	M208T	Developmental delay, hypotonia, myopathy, failure to thrive	Uncertain significance · reported	0
m.6544A>C	N214T	Possible association with sepsis	Reported	0
m.6547T>C	L215P	Leigh Syndrome	Reported	4
m.6579G>A	G226Term	Leigh Syndrome	Reported	0
m.6597C>A	Q232K	MELAS-like syndrome	Reported	0
m.6649C>T	P249L	Possible association with sepsis	Reported	0
m.6663A>G	I254V	Prostate Cancer	Reported	230
m.6698A>-	K-K_frameshift	Myopathy	Reported	0
m.6708G>A	G269Term	MM & Rhabdomyolysis	Reported	0
m.6721T>C	M273T	Acquired Idiopathic Sideroblastic Anemia	Uncertain significance · reported	0
m.6742T>C	I280T	Acquired Idiopathic Sideroblastic Anemia	Uncertain significance · reported	0
m.6853G>C	G317A	Seizures +myopathy + speech delay	Reported	1
m.6860A>C	K319N	Dilated Cardiomyopathy	Reported	0
m.6930G>A	G343Term	Multisystem Disorder	Likely pathogenic · confirmed	0
m.6955G>A	G351D	Mild EXIT and MR	Reported	1
m.6962G>A	L353L	Possible helper variant for 15927A	Reported	1,587
m.7023G>A	V374M	MELAS-like syndrome	Reported	1
m.7041G>A	V380I	Prostate Cancer	Reported	6
m.7065G>A	A388T	Possible association with sepsis	Reported	0
m.7080T>C	F393L	Prostate Cancer / PCOS patient	Reported	70
m.7083A>G	I394V	Prostate Cancer	Reported	16
m.7158A>G	I419V	Prostate Cancer	Reported	63
m.7222A>G	Y440C	Mitochondrial myopathy	Uncertain significance · reported	0
m.7299A>G	M466V	LHON	Reported	90
m.7305A>C	M468L	Prostate Cancer	Reported	0
m.7379G>A	L492L	Possible association with sepsis	Reported	25
m.7402C>-	frameshift	Isolated complex IV deficiency	Reported	0
m.7443A>G	Term514G	DEAF	Uncertain significance · reported	1
m.7444G>A	Term514K	LHON / SNHL / DEAF modulator	Likely benign · reported	238
m.7445A>G	—	SNHL	Pathogenic · confirmed	1
m.7445A>G	Term514Term	SNHL	Pathogenic · confirmed	1
m.7445A>T	Term514S	SNHL	Uncertain significance · reported	4
m.7445A>T	—	SNHL	Uncertain significance · reported	4
m.7445A>C	Term514S	DEAF	Uncertain significance · reported	17
m.7445A>C	—	DEAF	Uncertain significance · reported	17