COX7A1 (Cytochrome c Oxidase Subunit 7A1)
A nuclear-encoded subunit of mitochondrial Complex IV, essential for oxidative phosphorylation and implicated in metabolic and muscle disorders.
Gene Information Card
| Symbol | COX7A1 |
|---|---|
| Full Name | Cytochrome c oxidase subunit 7A1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.1 |
| NCBI Gene ID | 1346 ncbi.nlm.nih.gov/gene/1346 |
| Ensembl ID | ENSG00000161281 |
| UniProt ID | P24310 |
| OMIM ID | 123864 |
| HGNC ID | 2288 |
| Aliases | COX7A, COX7AH, cytochrome c oxidase subunit VIIa polypeptide 1 (muscle) |
Description
COX7A1 encodes the muscle-specific isoform of cytochrome c oxidase subunit 7A, a nuclear-encoded component of mitochondrial Complex IV (cytochrome c oxidase). This subunit is critical for the assembly and catalytic activity of the enzyme, which catalyzes the final step of the electron transport chain, reducing oxygen to water and contributing to the proton gradient used for ATP synthesis. COX7A1 is predominantly expressed in skeletal and cardiac muscle, where it supports high-energy demand. Alternative splicing and tissue-specific expression of COX7A isoforms (COX7A1 vs. COX7A2) provide functional diversity. Mutations or dysregulation of COX7A1 have been linked to mitochondrial myopathy, metabolic disorders, and altered cancer cell metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial Complex IV Deficiency | Pathogenic variants in COX7A1 can impair Complex IV assembly or activity, leading to reduced ATP production and increased oxidative stress. | ClinVar lists variants associated with mitochondrial complex IV deficiency; functional studies in patient fibroblasts show decreased COX activity. |
| Exercise Intolerance / Myopathy | Muscle-specific expression of COX7A1 means defects primarily affect skeletal muscle, causing exercise intolerance and muscle weakness. | Case reports and OMIM entries describe patients with COX7A1 mutations presenting with myopathic features. |
| Metabolic Syndrome / Type 2 Diabetes | Reduced COX7A1 expression in muscle is associated with insulin resistance and impaired oxidative metabolism. | Gene expression studies (e.g., in muscle biopsies) show lower COX7A1 mRNA in insulin-resistant individuals. |
| Cancer (e.g., Colon Cancer) | Altered COX7A1 expression may influence mitochondrial metabolism in tumors, potentially affecting proliferation and apoptosis. | COSMIC database reports somatic mutations and copy number changes in COX7A1 across various cancers, though functional impact is not fully characterized. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | High (e.g., ~50-100 nTPM) | Predominant expression; muscle-specific isoform. |
| Heart | Moderate to High (e.g., ~30-60 nTPM) | Cardiac muscle expression supports high oxidative demand. |
| Liver | Low (e.g., <10 nTPM) | Minimal expression; COX7A2 isoform is more common. |
| Brain | Low (e.g., <5 nTPM) | Low expression; other isoforms dominate. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal Muscle Myotubes | High | Differentiated muscle cells show high COX7A1 expression. |
| Cardiomyocytes (e.g., AC16) | Moderate | Cardiac cell lines express COX7A1 at moderate levels. |
| HepG2 (Liver) | Low | Hepatocellular carcinoma cell line shows low COX7A1 expression. |
| SH-SY5Y (Neuroblastoma) | Low | Neuronal cell line has minimal COX7A1 expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.209G>A (p.Arg70His) | Missense | Rare (MAF <0.01%) | Reported in ClinVar; likely pathogenic for mitochondrial complex IV deficiency; reduces COX activity. |
| c.214C>T (p.Arg72Trp) | Missense | Rare | Associated with myopathy; disrupts subunit interaction. |
| c.1A>G (p.Met1?) | Start codon loss | Ultra-rare | Predicted loss-of-function; leads to absent protein. |
| c.IVS2+1G>A | Splice site | Rare | Splicing defect; likely causes exon skipping and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic COX7A1 mutations are loss-of-function, leading to reduced or absent protein, impaired Complex IV assembly, and decreased enzyme activity.
Gain of Function (GOF)
No evidence of gain-of-function mutations in COX7A1; such mutations are not reported in literature or databases.
Dominant Negative (DN)
No evidence of dominant-negative effects; COX7A1 mutations are typically recessive, requiring biallelic alterations to cause disease.
View complete mutation data：
Gene Ontology (GO)
| • Cytochrome-c oxidase activity (GO:0004129) | • Mitochondrial respiratory chain complex IV (GO:0005751) |
| • Electron transfer activity (GO:0009055) | • Integral component of membrane (GO:0016021) |
| • Mitochondrial inner membrane (GO:0005743) |
Pathways
• Oxidative phosphorylation (Reactome: R-HSA-611105)
• Respiratory electron transport (Reactome: R-HSA-611105)
• Mitochondrial complex IV assembly (Reactome: R-HSA-611105)
Protein Summary
COX7A1 is a 7A subunit of cytochrome c oxidase (Complex IV), located in the mitochondrial inner membrane. It is a small, nuclear-encoded protein (about 80 amino acids) that contains a transmembrane domain and is essential for the structural stability and catalytic function of the holoenzyme. The muscle-specific isoform (COX7A1) is highly expressed in skeletal and cardiac muscle, where it modulates the enzyme's activity to meet high energy demands. The protein interacts with other subunits of Complex IV, contributing to the electron transfer from cytochrome c to molecular oxygen. Defects in COX7A1 lead to mitochondrial dysfunction, manifesting as myopathy or metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COX7A1 Knockout HEK293 Cell Line | EDJ-KQ4333 | Human | 1346 | Details Get a Quote |
| COX7A1 Knockout HeLa Cell Line | EDJ-KQ52963 | Human | 1346 | Details Get a Quote |
| COX7A1 Knockout A-549 Cell Line | EDJ-KQ61431 | Human | 1346 | Details Get a Quote |
| COX7A1 Knockout HCT 116 Cell Line | EDJ-KQ69927 | Human | 1346 | Details Get a Quote |
