CHCHD4
Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 4
Gene Information Card
| Symbol | CHCHD4 |
|---|---|
| Full Name | Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 131474 ncbi.nlm.nih.gov/gene/131474 |
| Ensembl ID | ENSG00000163682 |
| UniProt ID | Q8N4Q1 |
| OMIM ID | 611065 |
| HGNC ID | 26587 |
| Aliases | MIA40, TIMM40, MIA40 homolog |
Description
CHCHD4 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 4), also known as MIA40, is a mitochondrial intermembrane space (IMS) protein that functions as a key oxidoreductase in the import and oxidative folding of cysteine-rich proteins. It facilitates the disulfide bond formation in substrate proteins, enabling their proper folding and retention within the IMS. CHCHD4 is essential for mitochondrial function and cellular redox homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial disease (multisystem) | Impaired oxidative folding due to CHCHD4 deficiency leads to mitochondrial dysfunction | PMID: 25609799 |
| Cancer (various types) | Altered CHCHD4 expression affects mitochondrial metabolism and apoptosis | PMID: 25944712 |
| Neurodegenerative disorders | Dysregulation of mitochondrial IMS protein import contributes to neuronal stress | PMID: 28886342 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Brain | 5.6 | Low |
| Skeletal muscle | 10.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.0 | High expression |
| HEK293 | 11.5 | Moderate expression |
| HepG2 | 9.8 | Moderate expression |
| SH-SY5Y | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.238C>T (p.Arg80Trp) | Missense | Rare | Impaired protein stability and reduced import activity |
| c.364G>A (p.Gly122Ser) | Missense | Rare | Decreased disulfide transfer activity |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of translation initiation |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg80Trp) reduce CHCHD4 stability and catalytic activity, impairing mitochondrial IMS protein import.
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)
Pathways
• Mitochondrial protein import (REACT_21300)
• Disulfide bond formation in the mitochondrial intermembrane space
Protein Summary
CHCHD4 (MIA40) is a 16 kDa protein localized to the mitochondrial intermembrane space. It contains a conserved CPC motif that mediates thiol-disulfide exchange with substrate proteins. CHCHD4 acts as an oxidoreductase, introducing disulfide bonds into newly imported IMS proteins, which is critical for their folding and retention. It also participates in redox signaling and apoptosis regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHCHD4 Knockout HEK293 Cell Line | EDJ-KQ51977 | Human | 131474 | Details Get a Quote |
| CHCHD4 Knockout HeLa Cell Line | EDJ-KQ58298 | Human | 131474 | Details Get a Quote |
| CHCHD4 Knockout A-549 Cell Line | EDJ-KQ66786 | Human | 131474 | Details Get a Quote |
| CHCHD4 Knockout HCT 116 Cell Line | EDJ-KQ75189 | Human | 131474 | Details Get a Quote |
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