UQCC4: A Key Assembly Factor for Mitochondrial Complex III
Explore the genomic context, expression patterns, and clinical relevance of the UQCC4 gene, a critical player in oxidative phosphorylation.
Gene Information Card
| Symbol | UQCC4 |
|---|---|
| Full Name | Ubiquinol-Cytochrome C Reductase Complex Assembly Factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 100130729 ncbi.nlm.nih.gov/gene/100130729 |
| Ensembl ID | ENSG00000214113 |
| UniProt ID | Q5TFF3 |
| OMIM ID | 617565 |
| HGNC ID | 43853 |
| Aliases | C3orf75, MGC26717 |
Description
UQCC4 encodes a small mitochondrial protein that functions as an assembly factor for ubiquinol-cytochrome c reductase (Complex III) in the electron transport chain. It is involved in the early steps of Complex III assembly, stabilizing the cytochrome b subunit and facilitating the incorporation of other subunits. UQCC4 is essential for normal mitochondrial respiration and ATP production.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex III deficiency, nuclear type 10 | Biallelic loss-of-function mutations in UQCC4 lead to defective Complex III assembly, resulting in reduced enzymatic activity and impaired oxidative phosphorylation. | ClinVar and OMIM (617565) report pathogenic variants in UQCC4 associated with this condition. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Skeletal Muscle | 10.1 | Medium |
| Liver | 8.5 | Low |
| Brain | 6.2 | Low |
| Kidney | 7.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.4 | High expression |
| HEK293 | 12.8 | Moderate expression |
| HepG2 | 9.3 | Low expression |
| K562 | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.238C>T (p.Arg80Ter) | Nonsense | Rare | Premature stop codon leading to loss of function |
| c.1A>G (p.Met1Val) | Missense | Rare | Disrupts translation initiation, likely loss of function |
| c.200T>C (p.Leu67Pro) | Missense | Rare | Alters protein structure, likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic variants in UQCC4 are loss-of-function, leading to reduced or absent protein and impaired Complex III assembly.
Gain of Function (GOF)
No gain-of-function mutations have been reported for UQCC4.
Dominant Negative (DN)
No dominant-negative effects have been described; the disease is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrial respiratory chain complex III assembly | • Protein binding |
| • Mitochondrion |
Pathways
• Oxidative phosphorylation (Reactome: R-HSA-611105)
• Mitochondrial complex III assembly (Reactome: R-HSA-611105)
Protein Summary
UQCC4 is a 12 kDa mitochondrial membrane protein localized to the inner mitochondrial membrane. It contains a single transmembrane domain and a conserved C-terminal domain. It interacts with UQCC1 and UQCC2 to form a complex that stabilizes the newly synthesized cytochrome b protein, facilitating its incorporation into Complex III. UQCC4 is essential for proper Complex III function and cellular respiration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UQCC4 Knockout HEK293 Cell Line | EDJ-KQ16041 | Human | 283951 | Details Get a Quote |
| UQCC4 Knockout A-549 Cell Line | EDJ-KQ47155 | Human | 283951 | Details Get a Quote |
| UQCC4 Knockout HCT 116 Cell Line | EDJ-KQ47156 | Human | 283951 | Details Get a Quote |
| UQCC4 Knockout HeLa Cell Line | EDJ-KQ47157 | Human | 283951 | Details Get a Quote |
