MT-CO1

Chr MTAR

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.

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismAR2 OMIM phenotypes

Clinical Summary— MT-CO1

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Gene-Disease Validity (ClinGen)

Leigh syndrome · MTLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.92top 5%

GOF

0.98top 5%

LOF

0.01100th %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

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

MITOMAP ↗

Variant	AA	Disease	Status	GenBank
m.5906G>A	M1M	MELAS/Leigh overlap Syndrome	Reported	0.000%
m.5911C>T	A3V	Prostate Cancer / PCOS patient	Reported	40.740%
m.5913G>A	D4N	Prostate Cancer / hypertension	Reported	85.780%
m.5920G>A	W6Term	Myoglobinuria / EXIT	Cfrm [LP]	0.000%
m.5935A>G	N11S	Prostate Cancer	Reported	0.150%
m.5973G>A	A24T	Prostate Cancer	Reported	2.450%
m.6020CGAGC>-	AELGQ-AGPATerm	Motor Neuron Disease	Reported	0.000%
m.6020C>A	A39A	Possible association with sepsis	Reported	0.000%
m.6081G>A	A60T	Prostate Cancer	Reported	0.150%
m.6145G>A	W81Term	Unspecified suspected mitochondrial disorder	Reported [VUS]	0.000%
m.6150G>A	V83I	Prostate Cancer / POAG (primary open-angle glaucoma) risk factor	Reported	39.370%
m.6253T>C	M117T	Prostate Cancer / enriched in POAG cohort / PCOS patient	Reported	95.430%
m.6261G>A	A120T	Prostate Cancer / LHON	Reported	79.340%
m.6267G>A	A122T	Prostate Cancer	Reported	16.240%
m.6285G>A	V128I	Prostate Cancer	Reported	20.830%
m.6307A>G	N135S	Asthenozoospermic infertility	Reported	0.460%
m.6328C>T	S142F	EXIT (Exercise Intolerance)	Reported [VUS]	0.000%
m.6340C>T	T146I	Prostate Cancer	Reported	16.390%
m.6367T>C	V155A	Possible association with sepsis	Reported	3.680%
m.6459T>C	W186R	Sepsis susceptibility	Reported	0.000%
m.6474A>G	T191A	Maternally inherited childhood epilepsy and ataxia	Reported	0.000%
m.6480G>A	V193I	Prostate Cancer / enriched in POAG cohort	Reported	25.120%
m.6489C>A	L196I	CO1 deficiency with epilepsia partialis continua	Reported	13.790%
m.6526T>C	M208T	Developmental delay, hypotonia, myopathy, failure to thrive	Reported [VUS]	0.000%
m.6544A>C	N214T	Possible association with sepsis	Reported	0.000%
m.6547T>C	L215P	Leigh Syndrome	Reported	0.610%
m.6579G>A	G226Term	Leigh Syndrome	Reported	0.000%
m.6597C>A	Q232K	MELAS-like syndrome	Reported	0.000%
m.6649C>T	P249L	Possible association with sepsis	Reported	0.000%
m.6663A>G	I254V	Prostate Cancer	Reported (~3% AF Lineage L)	32.930%
m.6698A>-	K-K_frameshift	Myopathy	Reported	0.000%
m.6708G>A	G269Term	MM & Rhabdomyolysis	Reported	0.000%
m.6721T>C	M273T	Acquired Idiopathic Sideroblastic Anemia	Reported [VUS]	0.000%
m.6742T>C	I280T	Acquired Idiopathic Sideroblastic Anemia	Reported [VUS]	0.000%
m.6853G>C	G317A	Seizures +myopathy + speech delay	Reported	0.150%
m.6860A>C	K319N	Dilated Cardiomyopathy	Reported	0.000%
m.6930G>A	G343Term	Multisystem Disorder	Cfrm [LP]	0.000%
m.6955G>A	G351D	Mild EXIT and MR	Reported	0.150%
m.6962G>A	L353L	Possible helper variant for 15927A	Reported	242.930%
m.7023G>A	V374M	MELAS-like syndrome	Reported	0.150%
m.7041G>A	V380I	Prostate Cancer	Reported	0.920%
m.7065G>A	A388T	Possible association with sepsis	Reported	0.000%
m.7080T>C	F393L	Prostate Cancer / PCOS patient	Reported	10.570%
m.7083A>G	I394V	Prostate Cancer	Reported	2.450%
m.7158A>G	I419V	Prostate Cancer	Reported	9.340%
m.7222A>G	Y440C	Mitochondrial myopathy	Reported [VUS]	0.000%
m.7299A>G	M466V	LHON	Reported	13.480%
m.7305A>C	M468L	Prostate Cancer	Reported	0.000%
m.7379G>A	L492L	Possible association with sepsis	Reported	3.680%
m.7402C>-	frameshift	Isolated complex IV deficiency	Reported	0.000%
m.7443A>G	Term514G	DEAF	Reported [VUS]	0.150%
m.7444G>A	Term514K	LHON / SNHL / DEAF modulator	Reported [LB]	36.300%
m.7445A>T	—	SNHL	Reported [VUS]	0.610%
m.7445A>G	Term514Term	SNHL	Cfrm [P]	0.150%
m.7445A>C	Term514S	DEAF	Reported [VUS]	2.600%
m.7445A>C	—	DEAF	Reported [VUS]	2.600%
m.7445A>T	Term514S	SNHL	Reported [VUS]	0.610%
m.7445A>G	—	SNHL	Cfrm [P]	0.150%