ATOX1 Gene

Name	antioxidant 1 copper chaperone
Description	This gene encodes a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network for later incorporation to the ceruloplasmin. This protein also functions as an antioxidant against superoxide and hydrogen peroxide, and therefore, may play a significant role in cancer carcinogenesis. Because of its cytogenetic location, this gene represents a candidate gene for 5q-syndrome. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATOX1 is a multifunctional protein that plays a central role in the maintenance of cellular copper homeostasis. In its classical role as a copper chaperone, ATOX1 binds Cu(I) in the cytosol and delivers it to copper‐transporting ATPases (such as ATP7A and ATP7B), thereby ensuring the proper metallation of enzymes and facilitating copper efflux during conditions of excess copper ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. More recently, ATOX1 has been demonstrated to act as a copper‐dependent transcription factor. Upon copper stimulation, ATOX1 translocates to the nucleus where it directly binds to promoter regions—such as that of extracellular superoxide dismutase (SOD3) and the NADPH oxidase organizer p47^phox—to upregulate gene expression involved in antioxidant defense, cell proliferation, and neovascularization ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]. In addition, the redox state of ATOX1—regulated by the intracellular glutathione/glutathione disulfide balance and modulated by glutaredoxin—affects its copper‐binding properties and, consequently, its ability to shuttle copper and regulate downstream processes ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]. Furthermore, ATOX1 has been implicated in mediating the cellular response to chemotherapeutic agents; for example, its involvement in the polyubiquitination of the copper importer CTR1 influences cisplatin uptake and resistance ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. Finally, by coordinating copper delivery via ATP7A, ATOX1 also contributes to processes such as cancer cell migration through activation of downstream targets like lysyl oxidase, highlighting its relevance in tumor progression ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]. Taken together, these findings establish ATOX1 as a pivotal regulator that integrates copper transport, redox signaling, transcriptional control, and cellular responses to stress, thereby influencing diverse physiological and pathophysiological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shinichi Itoh, Ha Won Kim, Osamu Nakagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M709463200"}], "href": "https://doi.org/10.1074/jbc.M709463200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18245776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18245776"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Iqbal Hamza, Joseph Prohaska, Jonathan D Gitlin "}, {"type": "b", "children": [{"type": "t", "text": "Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0336230100"}], "href": "https://doi.org/10.1073/pnas.0336230100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12538877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12538877"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shinichi Itoh, Kiyoshi Ozumi, Ha Won Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mechanism for regulation of extracellular SOD transcription and activity by copper: role of antioxidant-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2008.09.039"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2008.09.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18977292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18977292"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gin-Fu Chen, Varadarajan Sudhahar, Seock-Won Youn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Copper Transport Protein Antioxidant-1 Promotes Inflammatory Neovascularization via Chaperone and Transcription Factor Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep14780"}], "href": "https://doi.org/10.1038/srep14780"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26437801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26437801"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuta Hatori, Sara Clasen, Nesrin M Hasan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional partnership of the copper export machinery and glutathione balance in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.381178"}], "href": "https://doi.org/10.1074/jbc.M112.381178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22648419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22648419"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jens Brose, Sharon La Fontaine, Anthony G Wedd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Redox sulfur chemistry of the copper chaperone Atox1 is regulated by the enzyme glutaredoxin 1, the reduction potential of the glutathione couple GSSG/2GSH and the availability of Cu(I)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metallomics (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1039/c4mt00020j"}], "href": "https://doi.org/10.1039/c4mt00020j"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24522867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24522867"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Roohangiz Safaei, Mohammad H Maktabi, Brian G Blair, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of the loss of Atox1 on the cellular pharmacology of cisplatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inorg Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jinorgbio.2008.11.012"}], "href": "https://doi.org/10.1016/j.jinorgbio.2008.11.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19124158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19124158"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Stéphanie Blockhuys, Xiaolu Zhang, Pernilla Wittung-Stafshede "}, {"type": "b", "children": [{"type": "t", "text": "Single-cell tracking demonstrates copper chaperone Atox1 to be required for breast cancer cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1910722117"}], "href": "https://doi.org/10.1073/pnas.1910722117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31932435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31932435"}]}]}]}
Synonyms	HAH1, ATX1
Proteins	ATOX1_HUMAN
NCBI Gene ID	475
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ATOX1 has 8,895 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 120 datasets.

Click the + buttons to view associations for ATOX1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ATOX1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ATOX1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ATOX1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ATOX1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ATOX1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ATOX1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ATOX1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ATOX1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ATOX1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ATOX1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ATOX1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ATOX1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ATOX1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ATOX1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ATOX1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ATOX1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ATOX1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ATOX1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ATOX1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ATOX1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ATOX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ATOX1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ATOX1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ATOX1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ATOX1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ATOX1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ATOX1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ATOX1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ATOX1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ATOX1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ATOX1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ATOX1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ATOX1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ATOX1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ATOX1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ATOX1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ATOX1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ATOX1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing ATOX1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ATOX1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ATOX1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.