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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ATOX1
antioxidant 1 copper chaperone
Chromosome 5 · 5q33.1
NCBI Gene: 475Ensembl: ENSG00000177556.13HGNC: HGNC:798UniProt: O00244
104PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
copper ion bindingprotein bindingcopper chaperone activitycopper-dependent protein bindingneurodegenerative diseasemouth neoplasmbasal cell carcinomabreast cancer
✦AI Summary

ATOX1 (antioxidant 1 copper chaperone) is a cytosolic metallochaperone that delivers cuprous ions (Cu+) to copper ATPases ATP7A and ATP7B, functioning as a critical component of the CTR1-ATOX1-ATP7A/ATP7B copper homeostasis axis 1. The protein binds Cu+ through its conserved CxxC metal-binding motif involving Cys12 and Cys15 residues 2, enabling conformational flexibility for protein-protein interactions and copper transfer to partner proteins including CCS 3. Beyond copper transport, ATOX1 possesses transcription factor activity, regulating genes including CCND1, MDC1, and SOD3, thereby supporting cell proliferation and survival 4. ATOX1 protects cells against oxidative stress through multiple mechanisms: maintaining mitochondrial copper balance, facilitating mitophagy via DJ-1 interaction, and regulating antioxidant enzyme activity 5. Pathologically, ATOX1 dysregulation is implicated in cancer progression through altered copper-dependent signaling and metastatic capacity 4. In lymphoma, ATOX1 overexpression promotes proliferation via MAPK pathway activation in a copper-dependent manner 6. Additionally, ATOX1 oxidation and cisplatin binding influence chemotherapy resistance 7. Copper metabolism dysregulation involving ATOX1 is associated with neurodegenerative diseases, cardiovascular disease, and cancer 18.

Sources cited
1
ATOX1 delivers Cu+ to ATP7A/ATP7B in the CTR1-ATOX1-ATP7A/ATP7B route and is involved in copper homeostasis; copper imbalance causes neurodegenerative, cardiovascular, and other diseases
PMID: 32506322
2
ATOX1 copper binding involves Cys12 and Cys15 residues; protein exhibits conformational flexibility dependent on Cu(I) coordination
PMID: 32396355
3
ATOX1 exchanges copper ions with CCS; copper transfer requires functional Cu-binding cysteine residues
PMID: 25673218
4
ATOX1 has transcription factor activity regulating CCND1, MDC1, and SOD3; frequently overexpressed in cancer; supports cell proliferation and protects from oxidative stress; influences drug resistance
PMID: 40721800
5
ATOX1 protects neurons from oxidative stress after traumatic brain injury via DJ-1 interaction and mitochondrial mitophagy; copper-binding motif is critical for DJ-1 interaction
PMID: 38640584
6
ATOX1 is elevated in diffuse large B-cell lymphoma and promotes proliferation through copper-dependent MAPK pathway activation
PMID: 39036924
7
ATOX1 oxidation forms a disulfide bond preventing Cu(I) binding and antioxidant function; cisplatin binds to both Cu(I)-bound and oxidized forms of ATOX1, implicating it in chemotherapy resistance
PMID: 31500118
8
ATOX1 is involved in copper metabolism regulation affecting cell death pathways and autophagy; impaired copper metabolism implicated in Wilson disease and cancers
PMID: 37055935
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.33Weak
mouth neoplasmOpen Targets
0.28Weak
basal cell carcinomaOpen Targets
0.23Weak
breast cancerOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
diffuse large B-cell lymphomaOpen Targets
0.08Suggestive
cervical carcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
placenta praeviaOpen Targets
0.05Suggestive
triple-negative breast cancerOpen Targets
0.05Suggestive
colitisOpen Targets
0.04Suggestive
cerebral atherosclerosisOpen Targets
0.03Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
cataractOpen Targets
0.03Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
Wilson diseaseOpen Targets
0.02Suggestive
atherosclerosisOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCSProtein interaction99%ATP7AProtein interaction98%CPProtein interaction98%COMMD1Protein interaction98%COX11Protein interaction96%UBA52Protein interaction96%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
41%
Brain
37%
Lung
35%
Heart
30%
Ovary
26%
Gene Interaction Network
Click a node to explore
ATOX1CCSATP7ACPCOMMD1COX11UBA52
PROTEIN STRUCTURE
Preparing viewer…
PDB3IWL · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.36LoF Tolerant
pLIⓘ
0.08Tolerant
Observed/Expected LoF0.60 [0.29–1.36]
RankingsWhere ATOX1 stands among ~20K protein-coding genes
  • #4,571of 20,598
    Most Researched104 · top quartile
  • #14,204of 17,882
    Most Constrained (LOEUF)1.36
Genes detectedATOX1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Copper metabolism in cell death and autophagy.
PMID: 37055935
Autophagy · 2023
1.00
2
The molecular mechanisms of copper metabolism and its roles in human diseases.
PMID: 32506322
Pflugers Arch · 2020
0.90
3
Atox1 protects hippocampal neurons after traumatic brain injury via DJ-1 mediated anti-oxidative stress and mitophagy.
PMID: 38640584
Redox Biol · 2024
0.80
4
Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.
PMID: 40721800
J Exp Clin Cancer Res · 2025
0.70
5
Cuproptosis-related gene
PMID: 39036924
Biomol Biomed · 2024
0.60