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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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COX11
cytochrome c oxidase copper chaperone COX11
Chromosome 17 Β· 17q22
NCBI Gene: 1353Ensembl: ENSG00000166260.13HGNC: HGNC:2261UniProt: B4DEY8
54PubMed Papers
21Diseases
0Drugs
4Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrionprotein-containing complexprotein bindingATP biosynthetic processmitochondrial complex IV deficiency, nuclear type 23neurodegenerative diseasebreast carcinomabreast cancer
✦AI Summary

COX11 (cytochrome c oxidase copper chaperone COX11) functions as an essential assembly factor for mitochondrial respiratory chain complex IV (cytochrome c oxidase) 1. The protein acts as a metallochaperone that specifically delivers copper to the copper B site of COX1, facilitating proper complex IV assembly and function 1. COX11 is critical for maintaining cellular ATP production through oxidative phosphorylation, as demonstrated by studies showing that COX11 knockdown significantly decreases cellular ATP levels derived from respiration 2. Interestingly, these ATP deficits can be restored by coenzyme Q10 supplementation, suggesting COX11 has broader roles in mitochondrial energy metabolism beyond direct complex IV assembly 2. The protein localizes to mitochondria and shows evolutionary conservation from yeast to humans 3. Disease-wise, biallelic pathogenic variants in COX11 cause infantile-onset mitochondrial encephalopathies, classified as mitochondrial complex IV deficiency nuclear type 23 24. Additionally, alternative splicing of COX11 mediated by PTBP3 affects copper homeostasis and cellular sensitivity to cuproptosis, with implications for cancer progression 5. COX11 expression levels also correlate with patient outcomes in various cancers, including colorectal cancer where low expression associates with poor prognosis 6.

Sources cited
1
COX11 functions as assembly factor for complex IV and acts as metallochaperone delivering copper to COX1
PMID: 35750769
2
COX11 knockdown decreases cellular ATP levels and biallelic variants cause infantile mitochondrial encephalopathies
PMID: 36030551
3
COX11 shows evolutionary conservation and mitochondrial targeting
PMID: 9878253
4
Alternative splicing of COX11 affects copper homeostasis and cuproptosis sensitivity
PMID: 40270362
5
Novel COX11 variants cause Leigh-like features and affect oxidative stress sensitivity
PMID: 38068960
6
COX11 expression correlates with colorectal cancer prognosis and immune cell infiltration
PMID: 39901036
Disease Associationsβ“˜21
mitochondrial complex IV deficiency, nuclear type 23Open Targets
0.69Moderate
neurodegenerative diseaseOpen Targets
0.53Moderate
breast carcinomaOpen Targets
0.27Weak
breast cancerOpen Targets
0.23Weak
luminal A breast carcinomaOpen Targets
0.19Weak
Abnormality of the skeletal systemOpen Targets
0.19Weak
ovarian carcinomaOpen Targets
0.18Weak
contractureOpen Targets
0.16Weak
estrogen-receptor positive breast cancerOpen Targets
0.15Weak
psoriasisOpen Targets
0.12Weak
prostate carcinomaOpen Targets
0.08Suggestive
breast neoplasmOpen Targets
0.07Suggestive
agingOpen Targets
0.06Suggestive
hypothyroidismOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.04Suggestive
gastric cancerOpen Targets
0.04Suggestive
clonal hematopoiesisOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
type 2 diabetes mellitusOpen Targets
0.04Suggestive
jaw diseaseOpen Targets
0.03Suggestive
Mitochondrial complex IV deficiency, nuclear type 23UniProt
Pathogenic Variants4
NM_004375.5(COX11):c.35_36delinsG (p.Val12fs)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2024β†’ Residue 12
NM_004375.5(COX11):c.766dup (p.Thr256fs)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2024β†’ Residue 256
NM_004375.5(COX11):c.739C>A (p.Pro247Thr)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2024β†’ Residue 247
NM_004375.5(COX11):c.730G>C (p.Ala244Pro)Pathogenic
Mitochondrial complex IV deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2023β†’ Residue 244
View on ClinVar β†—
Related Genes
SURF1Protein interaction99%SCO1Protein interaction98%UQCRFS1Protein interaction98%SCO2Protein interaction98%ATOX1Protein interaction96%COX10Protein interaction93%
Tissue Expression6 tissues
Heart
100%
Brain
96%
Liver
86%
Ovary
83%
Lung
52%
Bone Marrow
46%
Gene Interaction Network
Click a node to explore
COX11SURF1SCO1UQCRFS1SCO2ATOX1COX10
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9Y6N1
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.79LoF Tolerant
pLIβ“˜
0.02Tolerant
Observed/Expected LoF0.51 [0.33–0.79]
RankingsWhere COX11 stands among ~20K protein-coding genes
  • #8,299of 20,598
    Most Researched54
  • #3,787of 5,498
    Most Pathogenic Variants4
  • #6,527of 17,882
    Most Constrained (LOEUF)0.79
Genes detectedCOX11
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Copper metabolism in cell death and autophagy.
PMID: 37055935
Autophagy Β· 2023
1.00
2
Targeting PTBP3-Mediated Alternative Splicing of COX11 Induces Cuproptosis for Inhibiting Gastric Cancer Peritoneal Metastasis.
PMID: 40270362
Adv Sci (Weinh) Β· 2025
0.90
3
Association of STXBP4/COX11 rs6504950 (G>A) polymorphism with breast cancer risk: evidence from 17,960 cases and 22,713 controls.
PMID: 22863968
Arch Med Res Β· 2012
0.80
4
Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy.
PMID: 36030551
Hum Mutat Β· 2022
0.70
5
Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain.
PMID: 9878253
Genomics Β· 1998
0.60