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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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COX19
cytochrome c oxidase assembly factor COX19
Chromosome 7 · 7p22.3
NCBI Gene: 90639Ensembl: ENSG00000240230.6HGNC: HGNC:28074UniProt: Q49B96
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingprotein folding chaperonemitochondrioncytosolneurodegenerative diseaseinflammatory bowel diseaseCrohn's diseasechronic obstructive pulmonary disease
✦AI Summary

COX19 is a mitochondrial assembly factor essential for cytochrome c oxidase (Complex IV) biogenesis in the electron transport chain. COX19 functions as a chaperone protein localized to the mitochondrial intermembrane space and cytoplasm 1, where it acts as a COX11 copper chaperone supporting copper coordination and stimulates SCO2-mediated metalation of COX2 2. In the absence of COX11, COX19 can directly deliver copper to the copper B site of COX1 2. Beyond its canonical mitochondrial role, COX19 regulates cellular copper homeostasis by transducing an SCO1-dependent redox signal to the copper exporter ATP7A 3. COX19 function is particularly critical during iron deficiency stress 4, and operates downstream of LRRK2 as a modulator of copper chaperone redox status in mitochondrial bioenergetics 5. Disease relevance includes potential involvement in Parkinson's disease pathogenesis, where pathogenic LRRK2 mutations disrupt the LRRK2-COX19 signaling axis impairing COX assembly 5. In cancer, COX19 overexpression promotes colorectal cancer progression by enhancing mitochondrial copper content and ATP production 6, 7. Notably, COX19 mutations were not identified in patients with isolated COX deficiency 8, suggesting other assembly factors remain to be characterized in human disease.

Sources cited
1
COX19 is a nuclear-encoded 11-kDa protein localized to cytoplasm and mitochondrial intermembrane space, required for post-translational COX assembly
PMID: 12171940
2
COX19 acts as a COX11 chaperone supporting copper coordination and stimulates SCO2-mediated metalation; can deliver copper to COX1 copper B site
PMID: 35750769
3
COX19 transduces SCO1-dependent redox signal from mitochondria to ATP7A to regulate cellular copper homeostasis
PMID: 23345593
4
COX19 function is particularly important for COX assembly under iron deficiency; influences copper and iron homeostasis in plants
PMID: 30778722
5
COX19 functions downstream of LRRK2 as upstream modulator of COX11 and SCO1 redox status; defective LRRK2-COX19 axis promotes neurodegeneration
PMID: 41621246
6
COX19 overexpression promotes colorectal cancer progression by enhancing mitochondrial copper content and ATP production
PMID: 38141772
7
COX19 promotes colon adenocarcinoma cell invasion and proliferation
PMID: 40391581
8
No COX19 mutations found in 53 patients with isolated COX deficiency, suggesting COX19 is not commonly involved in human COX deficiency
PMID: 15596615
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.49Moderate
inflammatory bowel diseaseOpen Targets
0.29Weak
Crohn's diseaseOpen Targets
0.06Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.05Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.03Suggestive
metabolic syndromeOpen Targets
0.02Suggestive
asthmaOpen Targets
0.02Suggestive
leprosyOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
migraine disorderOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.01Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.01Suggestive
ataxia telangiectasiaOpen Targets
0.01Suggestive
small cell osteogenic sarcomaOpen Targets
0.01Suggestive
osteoporosisOpen Targets
0.01Suggestive
type 2 diabetes mellitusOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.00Suggestive
Huntington diseaseOpen Targets
0.00Suggestive
colorectal carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CHCHD4Protein interaction100%COASYProtein interaction91%CYCSProtein interaction78%COA5Protein interaction76%GFERProtein interaction76%COX17Protein interaction76%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
52%
Lung
49%
Liver
49%
Heart
45%
Brain
29%
Gene Interaction Network
Click a node to explore
COX19CHCHD4COASYCYCSCOA5GFERCOX17
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q49B96
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.36 [0.74–1.91]
RankingsWhere COX19 stands among ~20K protein-coding genes
  • #13,874of 20,598
    Most Researched21
  • #17,331of 17,882
    Most Constrained (LOEUF)1.91
Genes detectedCOX19
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Studies of COX16, COX19, and PET191 in human cytochrome-c oxidase deficiency.
PMID: 15596615
Arch Neurol · 2004
1.00
2
COX19 Is a New Target of MACC1 and Promotes Colorectal Cancer Progression by Regulating Copper Transport in Mitochondria.
PMID: 38141772
J Nutr · 2024
0.90
3
The mitochondrial copper chaperone COX19 influences copper and iron homeostasis in arabidopsis.
PMID: 30778722
Plant Mol Biol · 2019
0.80
4
LRRK2 controls COX assembly through regulation of redox status of mitochondrial copper chaperones.
PMID: 41621246
Redox Biol · 2026
0.70
5
Differential Methylation Patterns Predict HBsAg Seroconversion in Hepatitis B Virus Reactivation Patients.
PMID: 40686026
Immunol Invest · 2025
0.60