COX1 (Cytochrome c Oxidase Subunit I): Genetics, Function, and Clinical Significance
A comprehensive biomedical overview of the mitochondrial-encoded COX1 gene, including genomic annotations, expression profiles, disease associations, and mutation data.
Gene Information Card
| Symbol | COX1 |
|---|---|
| Full Name | Cytochrome c oxidase subunit I (mitochondrially encoded) |
| Gene Type | Protein-coding (mitochondrial) |
| Chromosomal Location | Mitochondrial DNA (MT), position 5904–7445 (NC_012920.1) |
| NCBI Gene ID | 4512 ncbi.nlm.nih.gov/gene/4512 |
| Ensembl ID | ENSG00000198804 |
| UniProt ID | P00395 |
| OMIM ID | 516030 |
| HGNC ID | HGNC:7427 |
| Aliases | COI, MTCO1, cytochrome c oxidase polypeptide I, COX I |
Description
COX1 (also known as MT-CO1) is a mitochondrial-encoded gene that encodes the catalytic core subunit I of cytochrome c oxidase (Complex IV) in the electron transport chain. This enzyme is essential for oxidative phosphorylation, catalyzing the transfer of electrons from cytochrome c to molecular oxygen and contributing to the proton gradient that drives ATP synthesis. COX1 contains the heme a3 and CuB centers that form the oxygen reduction site. Mutations in COX1 are associated with various mitochondrial disorders, including Leber hereditary optic neuropathy, mitochondrial encephalomyopathy, and some cancers. The gene is located on the mitochondrial genome and is transcribed and translated within the mitochondrion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leber Hereditary Optic Neuropathy (LHON) | Pathogenic variants in MT-CO1 impair Complex IV activity, leading to reduced ATP production and increased reactive oxygen species in retinal ganglion cells, causing optic nerve degeneration. | ClinVar: Multiple pathogenic variants (e.g., m.6597A>G, m.6708G>A) reported; OMIM #535000. |
| Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) | COX1 mutations can disrupt Complex IV assembly or function, causing energy deficiency in high-demand tissues (brain, muscle), leading to lactic acidosis and stroke-like episodes. | ClinVar: Variants such as m.6597A>G associated with MELAS; OMIM #540000. |
| Cytochrome c Oxidase Deficiency | Biallelic or heteroplasmic pathogenic variants in COX1 reduce enzyme activity, leading to a spectrum of phenotypes including hypotonia, cardiomyopathy, and encephalopathy. | ClinVar: Multiple loss-of-function variants; OMIM #220110. |
| Colorectal Cancer | Somatic mutations in MT-CO1 have been identified in colorectal tumors, potentially contributing to metabolic reprogramming and tumor progression. | COSMIC: COSMIC mutation data show recurrent somatic variants (e.g., c.6597A>G) in colorectal cancer samples. |
| Prostate Cancer | Mitochondrial DNA mutations, including in COX1, are found in prostate cancer tissues, possibly affecting oxidative phosphorylation and apoptosis resistance. | COSMIC: Somatic mutations reported in prostate cancer; ClinVar lists some as variants of unknown significance. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High (nTPM ~ 2000) | High expression due to high energy demand. |
| Skeletal Muscle | High (nTPM ~ 1800) | High expression for ATP production. |
| Liver | Moderate (nTPM ~ 800) | Moderate expression; metabolic activity. |
| Brain | Moderate (nTPM ~ 700) | Expression varies by region; high in neurons. |
| Kidney | Moderate (nTPM ~ 600) | Moderate expression for active transport. |
| Lung | Low (nTPM ~ 300) | Lower expression relative to muscle. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | High (nTPM ~ 1500) | Cancer cell line with high mitochondrial activity. |
| K562 (leukemia) | Moderate (nTPM ~ 900) | Myelogenous leukemia line; moderate expression. |
| MCF7 (breast cancer) | Moderate (nTPM ~ 850) | Breast cancer line; expression varies. |
| HepG2 (liver cancer) | High (nTPM ~ 1200) | Hepatocellular carcinoma line; high metabolic rate. |
| A549 (lung cancer) | Low (nTPM ~ 400) | Lung carcinoma; lower expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| m.6597A>G (p.Asn? ) | Missense | Rare (found in LHON/MELAS cases) | Impairs Complex IV activity; associated with LHON and MELAS. |
| m.6708G>A (p.Val? ) | Missense | Rare (LHON) | Reduced COX activity; pathogenic in LHON. |
| m.7445A>G (3' UTR) | Non-coding | Rare (deafness, neuropathy) | Affects RNA processing; linked to sensorineural hearing loss. |
| c.6597A>G (somatic) | Missense | Somatic in colorectal cancer | May alter mitochondrial metabolism in tumors. |
| c.6708G>A (somatic) | Missense | Somatic in prostate cancer | Potential role in cancer progression. |
Mutation functional classification
Loss of Function (LOF)
Pathogenic variants that reduce or abolish cytochrome c oxidase activity, leading to mitochondrial dysfunction and energy deficiency. Examples include m.6597A>G and m.6708G>A, which are associated with LHON and MELAS.
Gain of Function (GOF)
No clear gain-of-function mutations reported for COX1. Some somatic variants may confer a proliferative advantage in cancer, but mechanisms are not fully defined.
Dominant Negative (DN)
Mitochondrial heteroplasmy can result in dominant-negative effects if mutant mtDNA copies exceed a threshold, impairing Complex IV assembly and function.
View complete mutation data：
Gene Ontology (GO)
| • Cytochrome-c oxidase activity (GO:0004129) | • Electron transfer activity (GO:0009055) |
| • Metal ion binding (GO:0046872) | • Mitochondrial inner membrane (GO:0005743) |
| • Respiratory chain complex IV (GO:0005751) | • Oxidation-reduction process (GO:0055114) |
| • ATP synthesis coupled electron transport (GO:0042775) |
Pathways
• Oxidative phosphorylation (KEGG: hsa00190)
• Electron transport chain (Reactome: R-HSA-611105)
• Respiratory electron transport (Reactome: R-HSA-163200)
Protein Summary
COX1 is a 57 kDa protein (513 amino acids) localized to the mitochondrial inner membrane. It is the largest and most conserved subunit of cytochrome c oxidase, containing the heme a3 and CuB binuclear center where oxygen is reduced to water. The protein is synthesized within the mitochondrion and requires assembly factors for proper incorporation into Complex IV. COX1 also plays a role in proton pumping across the membrane, contributing to the proton motive force used for ATP synthesis. Defects in COX1 lead to impaired oxidative phosphorylation and are linked to a range of mitochondrial diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COX1 Knockout HEK293 Cell Line | EDJ-KQ5251 | Human | 4512 | Details Get a Quote |
| COX14 Knockout HEK293 Cell Line | EDJ-KQ10295 | Human | 84987 | Details Get a Quote |
| COX19 Knockout HEK293 Cell Line | EDJ-KQ10625 | Human | 90639 | Details Get a Quote |
| COX16 Knockout HEK293 Cell Line | EDJ-KQ10994 | Human | 51241 | Details Get a Quote |
| COX18 Knockout HEK293 Cell Line | EDJ-KQ12986 | Human | 285521 | Details Get a Quote |
| COX19 Knockout A-549 Cell Line | EDJ-KQ38121 | Human | 90639 | Details Get a Quote |
| COX19 Knockout HCT 116 Cell Line | EDJ-KQ38122 | Human | 90639 | Details Get a Quote |
| COX1 Knockout A-549 Cell Line | EDJ-KQ28284 | Human | 4512 | Details Get a Quote |
| COX1 Knockout HCT 116 Cell Line | EDJ-KQ28285 | Human | 4512 | Details Get a Quote |
| COX1 Knockout HeLa Cell Line | EDJ-KQ28286 | Human | 4512 | Details Get a Quote |
| COX19 Knockout HeLa Cell Line | EDJ-KQ36820 | Human | 90639 | Details Get a Quote |
| COX14 Knockout A-549 Cell Line | EDJ-KQ37566 | Human | 84987 | Details Get a Quote |
| COX14 Knockout HCT 116 Cell Line | EDJ-KQ37567 | Human | 84987 | Details Get a Quote |
| COX14 Knockout HeLa Cell Line | EDJ-KQ37568 | Human | 84987 | Details Get a Quote |
| COX16 Knockout A-549 Cell Line | EDJ-KQ38839 | Human | 51241 | Details Get a Quote |
