UQCRFS1: Rieske Iron-Sulfur Protein of Complex III
Mitochondrial respiratory chain subunit and disease-associated gene
Gene Information Card
| Symbol | UQCRFS1 |
|---|---|
| Full Name | Ubiquinol-Cytochrome c Reductase, Rieske Iron-Sulfur Polypeptide 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q12 |
| NCBI Gene ID | 7386 ncbi.nlm.nih.gov/gene/7386 |
| Ensembl ID | ENSG00000104879 |
| UniProt ID | P47985 |
| OMIM ID | 191327 |
| HGNC ID | 12585 |
| Aliases | RISP, UQCRFS1P, MC3DN9 |
Description
UQCRFS1 encodes the Rieske iron-sulfur protein (RISP), a critical component of mitochondrial respiratory chain complex III (cytochrome bc1 complex). RISP transfers electrons from ubiquinol to cytochrome c, coupling electron transport to proton translocation across the inner mitochondrial membrane. Mutations in UQCRFS1 cause mitochondrial complex III deficiency, nuclear type 9 (MC3DN9), presenting with lactic acidosis, hypotonia, and encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex III deficiency, nuclear type 9 (MC3DN9) | Loss-of-function mutations impair complex III assembly/activity, reducing ATP production and causing oxidative stress | OMIM #616111; ClinVar pathogenic variants |
| Leigh syndrome | Complex III deficiency leads to neurodegeneration and basal ganglia lesions | Case reports with UQCRFS1 variants |
| Cardiomyopathy | Complex III dysfunction in cardiac muscle causes energy deficit | Rare association; functional studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 45.2 | High |
| Skeletal Muscle | 38.7 | High |
| Liver | 22.1 | Medium |
| Brain | 18.5 | Medium |
| Kidney | 15.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 32.1 | High expression |
| HeLa | 28.4 | High expression |
| HepG2 | 20.7 | Medium expression |
| K562 | 12.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.248G>A (p.Gly83Asp) | Missense | Rare | Loss of iron-sulfur cluster binding, reduced complex III activity |
| c.364C>T (p.Arg122Trp) | Missense | Rare | Impaired protein stability and assembly |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Most reported UQCRFS1 mutations are loss-of-function, reducing complex III activity and mitochondrial respiration.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; recessive inheritance pattern.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KEGG hsa00190 - Oxidative phosphorylation
• Reactome R-HSA-611105 - Respiratory electron transport
• Reactome R-HSA-1428517 - The citric acid (TCA) cycle and respiratory electron transport
Protein Summary
The Rieske iron-sulfur protein (RISP) is a 274-amino acid nuclear-encoded mitochondrial protein. It contains a [2Fe-2S] cluster coordinated by two cysteine and two histidine residues, essential for electron transfer within complex III. RISP is anchored to the inner mitochondrial membrane via a transmembrane domain and interacts with cytochrome b and c1 subunits. Defects in RISP disrupt complex III assembly and activity, leading to mitochondrial disease.
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