COX4I2
Cytochrome c Oxidase Subunit 4 Isoform 2
Gene Information Card
| Symbol | COX4I2 |
|---|---|
| Full Name | cytochrome c oxidase subunit 4 isoform 2 (lung) |
| Gene Type | protein-coding |
| Chromosomal Location | 20q11.21 |
| NCBI Gene ID | 84701 ncbi.nlm.nih.gov/gene/84701 |
| Ensembl ID | ENSG00000131055 |
| UniProt ID | Q96KJ9 |
| OMIM ID | 607976 |
| HGNC ID | 16232 |
| Aliases | COX4-2, COX4L2, COX4B |
Description
COX4I2 encodes an isoform of cytochrome c oxidase subunit 4, a nuclear-encoded component of mitochondrial complex IV (cytochrome c oxidase). This isoform is predominantly expressed in lung and is induced under hypoxic conditions, replacing the ubiquitous COX4I1 isoform to optimize electron transport chain efficiency in low oxygen. The protein is essential for mitochondrial respiration and ATP production.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex IV deficiency | Loss-of-function mutations in COX4I2 impair cytochrome c oxidase activity, reducing ATP synthesis and causing tissue-specific energy failure. | ClinVar, OMIM |
| Lung cancer | Altered COX4I2 expression may contribute to hypoxic adaptation in lung tumors, promoting survival under low oxygen. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Heart | 3.2 | Low |
| Liver | 1.1 | Not detected |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.3 | High expression; hypoxia-inducible |
| HEK 293 | 2.1 | Low baseline expression |
| HeLa | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.214C>T (p.Arg72Trp) | Missense | <0.01% | Likely loss of function; associated with complex IV deficiency |
| c.337G>A (p.Gly113Ser) | Missense | <0.01% | Uncertain significance; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg72Trp) reduce cytochrome c oxidase activity, leading to mitochondrial dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described for COX4I2.
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) |
| • mitochondrion (GO:0005739) |
Pathways
• KEGG: hsa00190 - Oxidative phosphorylation
• Reactome: R-HSA-611105 - Respiratory electron transport
Protein Summary
COX4I2 is a 171-amino acid protein (UniProt Q96KJ9) that localizes to the mitochondrial inner membrane. It is a regulatory subunit of cytochrome c oxidase (complex IV), modulating enzyme activity in response to oxygen availability. The protein contains a transmembrane domain and interacts with other COX subunits to form the functional holoenzyme.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COX4I2 Knockout HEK293 Cell Line | EDJ-KQ10173 | Human | 84701 | Details Get a Quote |
| COX4I2 Knockout HeLa Cell Line | EDJ-KQ57654 | Human | 84701 | Details Get a Quote |
| COX4I2 Knockout A-549 Cell Line | EDJ-KQ66152 | Human | 84701 | Details Get a Quote |
| COX4I2 Knockout HCT 116 Cell Line | EDJ-KQ74579 | Human | 84701 | Details Get a Quote |
