COX5A: Cytochrome c Oxidase Subunit 5A
Mitochondrial Complex IV Nuclear-Encoded Subunit
Gene Information Card
| Symbol | COX5A |
|---|---|
| Full Name | Cytochrome c oxidase subunit 5A |
| Gene Type | protein-coding |
| Chromosomal Location | 15q24.2 |
| NCBI Gene ID | 9377 ncbi.nlm.nih.gov/gene/9377 |
| Ensembl ID | ENSG00000137806 |
| UniProt ID | P20674 |
| OMIM ID | 603773 |
| HGNC ID | 2267 |
| Aliases | COX, COX-VA, MC4DN20 |
Description
COX5A encodes a nuclear-encoded subunit of cytochrome c oxidase (Complex IV), the terminal enzyme of the mitochondrial respiratory chain. This subunit is essential for the assembly and catalytic activity of the holoenzyme, which transfers electrons from cytochrome c to molecular oxygen, contributing to the proton gradient that drives ATP synthesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex IV deficiency, nuclear type 20 (MC4DN20) | Loss-of-function mutations in COX5A impair complex IV assembly and activity, leading to reduced ATP production and oxidative stress. | OMIM #619064; ClinVar |
| Leigh syndrome | COX5A mutations cause complex IV deficiency, a common biochemical hallmark of Leigh syndrome, resulting in neurodegeneration. | PubMed; NCBI Gene |
| Cardiomyopathy | Complex IV deficiency due to COX5A variants can manifest as hypertrophic cardiomyopathy in infancy. | OMIM; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 28.5 | High |
| Skeletal Muscle | 22.3 | High |
| Liver | 12.1 | Medium |
| Brain | 10.8 | Medium |
| Kidney | 9.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| HEK293 | 14.8 | Embryonic kidney cells |
| SH-SY5Y | 12.5 | Neuroblastoma cell line |
| HepG2 | 11.9 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.154C>T (p.Arg52Trp) | Missense | Rare | Loss of complex IV activity; associated with MC4DN20 |
| c.287A>G (p.Tyr96Cys) | Missense | Rare | Impaired subunit assembly; Leigh syndrome phenotype |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of protein; severe mitochondrial disease |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish COX5A protein function, leading to complex IV deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported for COX5A.
Dominant Negative (DN)
No dominant-negative mutations reported; COX5A mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • cytochrome-c oxidase activity (GO:0004129) | • mitochondrial inner membrane (GO:0005743) |
| • integral component of membrane (GO:0016021) | • oxidative phosphorylation (GO:0006119) |
| • respiratory electron transport chain (GO:0022904) |
Pathways
• KEGG: hsa00190 - Oxidative phosphorylation
• Reactome: R-HSA-611105 - Respiratory electron transport
• Reactome: R-HSA-163200 - Formation of ATP by chemiosmotic coupling
Protein Summary
COX5A is a 12.5 kDa nuclear-encoded subunit of cytochrome c oxidase (Complex IV). It is located in the mitochondrial inner membrane and is required for the structural integrity and catalytic function of the enzyme. The protein contains a mitochondrial targeting presequence that is cleaved upon import. COX5A interacts with other subunits to form the holoenzyme complex, which catalyzes the reduction of oxygen to water.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COX5A Knockout HEK293 Cell Line | EDJ-KQ6566 | Human | 9377 | Details Get a Quote |
| COX5A Knockout HCT 116 Cell Line | EDJ-KQ30770 | Human | 9377 | Details Get a Quote |
| COX5A Knockout HeLa Cell Line | EDJ-KQ30771 | Human | 9377 | Details Get a Quote |
| COX5A Knockout A-549 Cell Line | EDJ-KQ63625 | Human | 9377 | Details Get a Quote |
