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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
COX14
cytochrome c oxidase assembly factor COX14
Chromosome 12 Β· 12q13.12
NCBI Gene: 84987Ensembl: ENSG00000178449.10HGNC: HGNC:28216UniProt: Q96I36
19PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingprotein folding chaperonemitochondrial respiratory chain complex IV assemblymitochondrionIsolated cytochrome C oxidase deficiencyleigh syndrome due to mitochondrial complex iv deficiencymitochondrial complex IV deficiency, nuclear type 10hypertension
✦AI Summary

COX14 is a core component of the MITRAC complex that regulates cytochrome c oxidase (complex IV) assembly by coordinating early assembly steps with mitochondrial COX1 synthesis 1. COX14 functions as a translational regulator of COX1, the central mitochondrial-encoded subunit of complex IV 1. Mechanistically, COX14 forms an early assembly intermediate with newly synthesized COX1 and cooperates with assembly factors COA3 and CMC1 to stabilize COX1 prior to incorporation of nuclear-encoded subunits 23. This stabilization occurs independently of metallation factors, suggesting COX14's primary role is COX1 turnover regulation rather than cofactor insertion 2. Mutations in COX14 cause mitochondrial complex IV deficiency (nuclear type 10), a severe mitochondrial disorder 3. In COX14-deficient mice, impaired COX1 translation leads to complex IV dysfunction, triggering increased reactive oxygen species production and secondary mitochondrial RNA release into the cytosol, causing RIG-I-mediated liver inflammation and tissue-specific pathologies 4. The interdependence between COX14 and COA3 demonstrates their coordinated roles in early complex IV biogenesis 3. Notably, disease severity varies by tissue, with some patients showing milder phenotypes including neuropathy, exercise intolerance, obesity, and short stature 3.

Sources cited
1
COX14 is the human ortholog of yeast COX14 and negatively regulates translation of cytochrome c oxidase subunit COX1
PMID: 22356826
2
COX14 forms an early complex IV assembly intermediate with COX1 and stabilizes newly synthesized COX1 prior to incorporation of COX4 and COX5a subunits, independent of metallation factors
PMID: 28082314
3
COA3 and COX14 are interdependent COX assembly factors that stabilize COX1; mutations in COA3 cause isolated complex IV deficiency with variable clinical severity
PMID: 25604084
4
COX14 mutations impair COX1 translation, causing complex IV deficiency with increased ROS production and secondary mitochondrial RNA release triggering RIG-I-mediated liver inflammation
PMID: 39134548
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
Isolated cytochrome C oxidase deficiencyOpen Targets
0.57Moderate
leigh syndrome due to mitochondrial complex iv deficiencyOpen Targets
0.48Moderate
mitochondrial complex IV deficiency, nuclear type 10Open Targets
0.44Moderate
hypertensionOpen Targets
0.27Weak
Varicose veinsOpen Targets
0.06Suggestive
essential hypertensionOpen Targets
0.03Suggestive
cardiovascular diseaseOpen Targets
0.03Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
Increased blood pressureOpen Targets
0.03Suggestive
fibromuscular dysplasiaOpen Targets
0.02Suggestive
systemic juvenile idiopathic arthritisOpen Targets
0.02Suggestive
prostate cancerOpen Targets
0.01Suggestive
asthmaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
lactic acidosisOpen Targets
0.01Suggestive
mitochondrial diseaseOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.00Suggestive
prostate adenocarcinomaOpen Targets
0.00Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.00Suggestive
Mitochondrial complex IV deficiency, nuclear type 10UniProt
Pathogenic Variants2
NM_032901.4(COX14):c.81dup (p.Tyr28fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2015β†’ Residue 28
NM_032901.4(COX14):c.57G>A (p.Met19Ile)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 10
β˜†β˜†β˜†β˜†2012β†’ Residue 19
View on ClinVar β†—
Related Genes
CMC1Shared pathway100%UQCR10Protein interaction100%COX5AProtein interaction100%NDUFS5Protein interaction96%COA6Protein interaction95%COA5Protein interaction84%
Tissue Expression6 tissues
Heart
100%
Liver
76%
Lung
39%
Ovary
32%
Brain
28%
Bone Marrow
20%
Gene Interaction Network
Click a node to explore
COX14CMC1UQCR10COX5ANDUFS5COA6COA5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96I36
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.20LoF Tolerant
pLIβ“˜
0.22Tolerant
Observed/Expected LoF0.47 [0.21–1.20]
RankingsWhere COX14 stands among ~20K protein-coding genes
  • #14,388of 20,598
    Most Researched19
  • #4,558of 5,498
    Most Pathogenic Variants2
  • #12,644of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedCOX14
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in mouse liver.
PMID: 39134548
Nat Commun Β· 2024
1.00
2
Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase.
PMID: 22356826
Genome Biol Β· 2012
0.90
3
Intracranial mesenchymal tumor with (novel) COX14::PTEN rearrangement.
PMID: 37312212
Acta Neuropathol Commun Β· 2023
0.80
4
A
PMID: 28082314
EMBO Rep Β· 2017
0.70
5
Inactivation of PDH can Reduce Anaplastic Thyroid Cancer Cells' Sensitivity to Artemisinin.
PMID: 34515013
Anticancer Agents Med Chem Β· 2022
0.60