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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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COX6C
cytochrome c oxidase subunit 6C
Chromosome 8 · 8q22.2
NCBI Gene: 1345Ensembl: ENSG00000164919.12HGNC: HGNC:2285UniProt: A0A024R9B7
65PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmitochondrial membranemitochondrionmitochondrial inner membraneneurodegenerative diseasediabetes mellitussmall cell lung carcinomalung adenocarcinoma
✦AI Summary

COX6C encodes cytochrome c oxidase subunit 6C, a nuclear-encoded component of mitochondrial complex IV that plays a critical role in oxidative phosphorylation 1. As part of the electron transport chain's final step, COX6C contributes to the transfer of electrons from reduced cytochrome c to molecular oxygen, generating ATP through oxidative phosphorylation 1. The protein requires nuclear translation followed by mitochondrial transport to form the functional COX complex 1. COX6C expression is regulated by specific intron-dependent mechanisms, with DAZAP1 binding to its mRNA and suppressing pre-mRNA splicing efficiency, thereby controlling COX6C protein levels and mitochondrial energy production 2. Disease relevance is significant, as COX6C dysregulation occurs in multiple pathological conditions. Copy number amplification at 8q22.2 drives COX6C overexpression in lung adenocarcinoma, promoting cell proliferation through ROS-AMPK signaling and mitotic regulation 3. Conversely, COX6C downregulation is associated with missed abortion, where reduced expression correlates with decreased mitochondrial function 4. In multiple myeloma, elevated COX6C expression promotes cell proliferation by maintaining mitochondrial structure and ATP levels 5. COX6C also serves as a biomarker in sarcopenia, where decreased expression reflects mitochondrial dysfunction in age-related muscle loss 6. These findings establish COX6C as both a critical metabolic regulator and potential therapeutic target.

Sources cited
1
COX6C encodes cytochrome c oxidase subunit 6C, a nuclear-encoded component of mitochondrial complex IV that plays a critical role in oxidative phosphorylation .
PMID: 33527004
2
COX6C expression is regulated by specific intron-dependent mechanisms, with DAZAP1 binding to its mRNA and suppressing pre-mRNA splicing efficiency, thereby controlling COX6C protein levels and mitochondrial energy production .
PMID: 29505834
3
Copy number amplification at 8q22.2 drives COX6C overexpression in lung adenocarcinoma, promoting cell proliferation through ROS-AMPK signaling and mitotic regulation .
PMID: 38242874
4
Conversely, COX6C downregulation is associated with missed abortion, where reduced expression correlates with decreased mitochondrial function .
PMID: 35605648
5
In multiple myeloma, elevated COX6C expression promotes cell proliferation by maintaining mitochondrial structure and ATP levels .
PMID: 41502258
6
COX6C also serves as a biomarker in sarcopenia, where decreased expression reflects mitochondrial dysfunction in age-related muscle loss .
PMID: 41320776
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.55Moderate
diabetes mellitusOpen Targets
0.24Weak
small cell lung carcinomaOpen Targets
0.21Weak
lung adenocarcinomaOpen Targets
0.20Weak
cutaneous melanomaOpen Targets
0.19Weak
esophageal squamous cell carcinomaOpen Targets
0.19Weak
breast carcinomaOpen Targets
0.19Weak
esophageal adenocarcinomaOpen Targets
0.19Weak
acute myeloid leukemiaOpen Targets
0.19Weak
colon adenocarcinomaOpen Targets
0.18Weak
colonic neoplasmOpen Targets
0.18Weak
colorectal adenocarcinomaOpen Targets
0.18Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.18Weak
Hepatobiliary NeoplasmOpen Targets
0.18Weak
HER2 Positive Breast CarcinomaOpen Targets
0.18Weak
leiomyomaOpen Targets
0.18Weak
lung carcinomaOpen Targets
0.18Weak
lymphoid neoplasmOpen Targets
0.18Weak
pancreatic ductal adenocarcinomaOpen Targets
0.18Weak
skin carcinomaOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NDUFB5Protein interaction100%NDUFA13Protein interaction100%NDUFB3Protein interaction100%NDUFA5Protein interaction100%NDUFB8Protein interaction100%NDUFA6Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Liver
53%
Brain
40%
Bone Marrow
35%
Ovary
29%
Lung
20%
Gene Interaction Network
Click a node to explore
COX6CNDUFB5NDUFA13NDUFB3NDUFA5NDUFB8NDUFA6
PROTEIN STRUCTURE
Preparing viewer…
PDB5Z62 · 3.60 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.23LoF Tolerant
pLIⓘ
0.33Tolerant
Observed/Expected LoF0.40 [0.16–1.23]
RankingsWhere COX6C stands among ~20K protein-coding genes
  • #7,157of 20,598
    Most Researched65
  • #12,960of 17,882
    Most Constrained (LOEUF)1.23
Genes detectedCOX6C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Differential expression and clinical significance of COX6C in human diseases.
PMID: 33527004
Am J Transl Res · 2021
1.00
2
COX6C expression driven by copy amplification of 8q22.2 regulates cell proliferation via mediation of mitosis by ROS-AMPK signaling in lung adenocarcinoma.
PMID: 38242874
Cell Death Dis · 2024
0.90
3
Quantitative proteomics and functional analysis identified novel targets for missed abortion.
PMID: 35605648
Exp Cell Res · 2022
0.80
4
Novel gene fusion of COX6C at 8q22-23 to HMGIC at 12q15 in a uterine leiomyoma.
PMID: 10679920
Genes Chromosomes Cancer · 2000
0.70
5
Specific intron-dependent loading of DAZAP1 onto the cox6c transcript suppresses pre-mRNA splicing efficacy and induces cell growth retardation.
PMID: 29505834
Gene · 2018
0.60