COA4
Cytochrome c Oxidase Assembly Factor 4
Gene Information Card
| Symbol | COA4 |
|---|---|
| Full Name | Cytochrome c Oxidase Assembly Factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.4 |
| NCBI Gene ID | 51257 ncbi.nlm.nih.gov/gene/51257 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q9BRX2 |
| OMIM ID | 617512 |
| HGNC ID | 25173 |
| Aliases | COX18, C11orf52, HSPC209 |
Description
COA4 (cytochrome c oxidase assembly factor 4) is a nuclear-encoded mitochondrial protein essential for the assembly of cytochrome c oxidase (Complex IV) in the mitochondrial respiratory chain. It facilitates the incorporation of copper ions into the COX2 subunit and stabilizes early assembly intermediates. COA4 is highly conserved across eukaryotes and is critical for oxidative phosphorylation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex IV deficiency | Loss-of-function mutations in COA4 impair COX assembly, leading to reduced Complex IV activity and ATP production. | OMIM #617512; PMID: 29276050 |
| Leigh syndrome | Biallelic COA4 variants cause early-onset mitochondrial encephalopathy with COX deficiency. | PMID: 29276050 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Skeletal muscle | 10.8 | Medium |
| Liver | 7.5 | Low |
| Brain | 6.2 | Low |
| Kidney | 8.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.5 | High expression |
| HeLa | 11.2 | Moderate expression |
| HepG2 | 9.8 | Moderate expression |
| K562 | 6.3 | Low expression |
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 function; disrupts protein stability and COX assembly |
| c.238_239del (p.Leu80Valfs*12) | Frameshift | Rare | Loss of function; premature truncation |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein translation |
Mutation functional classification
Loss of Function (LOF)
Most reported COA4 mutations are loss-of-function, leading to COX deficiency and mitochondrial disease.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • mitochondrial intermembrane space (GO:0005758) |
| • mitochondrial electron transport (GO:0006123) | • copper chaperone activity (GO:0016531) |
| • mitochondrial respiratory chain complex IV assembly (GO:0033615) |
Pathways
• Mitochondrial complex IV assembly (Reactome: R-HSA-611105)
• Respiratory electron transport (Reactome: R-HSA-611105)
• Oxidative phosphorylation (KEGG: hsa00190)
Protein Summary
COA4 is a small mitochondrial protein (approx. 12 kDa) localized to the intermembrane space. It acts as a copper chaperone specifically for the COX2 subunit of cytochrome c oxidase. COA4 binds copper ions and transfers them to the CuA site of COX2, a critical step for complex IV activity. Loss of COA4 leads to accumulation of COX assembly intermediates and severe respiratory chain deficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COA4 Knockout HEK293 Cell Line | EDJ-KQ11013 | Human | 51287 | Details Get a Quote |
| COA4 Knockout A-549 Cell Line | EDJ-KQ38890 | Human | 51287 | Details Get a Quote |
| COA4 Knockout HCT 116 Cell Line | EDJ-KQ38891 | Human | 51287 | Details Get a Quote |
| COA4 Knockout HeLa Cell Line | EDJ-KQ38892 | Human | 51287 | Details Get a Quote |
