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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UQCC3
ubiquinol-cytochrome c reductase complex assembly factor 3
Chromosome 11 · 11q12.3
NCBI Gene: 790955Ensembl: ENSG00000204922.6HGNC: HGNC:34399UniProt: Q6UW78
25PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphatidic acid bindingcardiolipin bindingmitochondrial electron transport, ubiquinol to cytochrome cmitochondrial respiratory chain complex III assemblyIsolated CoQ-cytochrome C reductase deficiencymitochondrial complex III deficiencyAbnormality of the skeletal systemsmoking initiation
✦AI Summary

UQCC3 is a mitochondrial inner membrane protein essential for assembly and stabilization of respiratory complex III (cytochrome bc1 complex), functioning downstream of assembly factors UQCC1 and UQCC2 1. The protein mediates cytochrome b recruitment and stabilization within the complex, thereby supporting mitochondrial ATP production 2. UQCC3 binds cardiolipin through its α-helices 2 and 3, regulating cardiolipin composition and cristae morphology 2. Beyond its canonical respiratory function, UQCC3 orchestrates mitochondrial bioenergetics by forming a positive feedback loop with reactive oxygen species to coordinate OXPHOS and glycolysis, particularly under hypoxic stress 3. Clinically, loss-of-function mutations in UQCC3 cause mitochondrial complex III deficiency (nuclear type 9), presenting with severe multisystem manifestations including lactic acidosis, hypoglycemia, hypotonia, and developmental delay 1. Complex III deficiency frequently manifests as combined respiratory chain dysfunction affecting complexes I and IV, suggesting UQCC3's role in supercomplex stabilization 4. Emerging evidence links reduced UQCC3 expression to malignant hyperthermia susceptibility, suggesting involvement in skeletal muscle mitochondrial dysfunction 5. Additionally, UQCC3 functions as an interferon-independent antiviral protein through OAS3-RNase L pathway activation 6, expanding its biological roles beyond energy metabolism.

Sources cited
1
UQCC3 mutation impairs complex III assembly, cytochrome b stability, and causes isolated complex III deficiency with lactic acidosis and developmental delay
PMID: 25008109
2
UQCC3 is a cardiolipin-binding mitochondrial inner membrane protein involved in bc1 complex assembly, supercomplex stabilization, and cristae morphology
PMID: 25605331
3
UQCC3 orchestrates OXPHOS and glycolysis through ROS feedback loop during hypoxia adaptation in hepatocellular carcinoma
PMID: 33147459
4
UQCC3 deficiency causes combined respiratory chain deficiency affecting complexes I and III
PMID: 28804536
5
UQCC3 expression is dysregulated in malignant hyperthermia susceptibility with sex-linked effects
PMID: 38542460
6
UQCC3 functions as an interferon-independent antiviral protein through OAS3-RNase L pathway
PMID: 28418037
7
UQCC3 is involved in respiratory supercomplex formation and mitoflash signaling regulation
PMID: 28630166
Disease Associationsⓘ21
Isolated CoQ-cytochrome C reductase deficiencyOpen Targets
0.52Moderate
mitochondrial complex III deficiencyOpen Targets
0.43Moderate
Abnormality of the skeletal systemOpen Targets
0.14Weak
smoking initiationOpen Targets
0.11Weak
neoplasmOpen Targets
0.08Suggestive
irritable bowel syndromeOpen Targets
0.05Suggestive
viral diseaseOpen Targets
0.04Suggestive
esophageal diseaseOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
Crohn's diseaseOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
adrenal cortex carcinomaOpen Targets
0.01Suggestive
mitochondrial diseaseOpen Targets
0.00Suggestive
ceroid lipofuscinosis, neuronal, 4 (Kufs type)Open Targets
0.00Suggestive
COVID-19–associated multisystem inflammatory syndrome in adultsOpen Targets
0.00Suggestive
gliomaOpen Targets
0.00Suggestive
neuronal ceroid lipofuscinosisOpen Targets
0.00Suggestive
schizophreniaOpen Targets
0.00Suggestive
squamous cell lung carcinomaOpen Targets
0.00Suggestive
Mitochondrial complex III deficiency, nuclear type 9UniProt
Pathogenic Variants1
NM_001085372.3(UQCC3):c.59T>A (p.Val20Glu)Pathogenic
Mitochondrial complex III deficiency nuclear type 9
☆☆☆☆2014→ Residue 20
View on ClinVar ↗
Related Genes
LYRM7Protein interaction70%UQCC2Protein interaction59%UQCC1Protein interaction56%UQCRFS1Shared pathway40%UQCRHLShared pathway33%UQCC4Shared pathway33%
Tissue Expression6 tissues
Liver
100%
Ovary
57%
Brain
50%
Lung
49%
Bone Marrow
30%
Heart
29%
Gene Interaction Network
Click a node to explore
UQCC3LYRM7UQCC2UQCC1UQCRFS1UQCRHLUQCC4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6UW78
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.08 [0.61–1.81]
RankingsWhere UQCC3 stands among ~20K protein-coding genes
  • #13,113of 20,598
    Most Researched25
  • #5,323of 5,498
    Most Pathogenic Variants1
  • #16,623of 17,882
    Most Constrained (LOEUF)1.81
Genes detectedUQCC3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability.
PMID: 25008109
Hum Mol Genet · 2014
1.00
2
An Association between OXPHOS-Related Gene Expression and Malignant Hyperthermia Susceptibility in Human Skeletal Muscle Biopsies.
PMID: 38542460
Int J Mol Sci · 2024
0.90
3
Mitochondrial UQCC3 Modulates Hypoxia Adaptation by Orchestrating OXPHOS and Glycolysis in Hepatocellular Carcinoma.
PMID: 33147459
Cell Rep · 2020
0.80
4
Deficiency of PHB complex impairs respiratory supercomplex formation and activates mitochondrial flashes.
PMID: 28630166
J Cell Sci · 2017
0.70
5
Combined Respiratory Chain Deficiency and
PMID: 28804536
Oxid Med Cell Longev · 2017
0.60