EYA3 Gene

HGNC Family	Phosphatases
Name	EYA transcriptional coactivator and phosphatase 3
Description	This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator and have a role during development. It can act as a mediator of chemoresistance and cell survival in Ewing sarcoma cells, where this gene is up-regulated via a micro-RNA that binds to the 3' UTR of the transcript. A similar protein in mice acts as a transcriptional activator. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Eyes absent 3 (EYA3) is a multifunctional protein that integrates dual activities as a transcriptional coactivator and phosphatase to orchestrate critical cellular processes. Its phosphatase function is exemplified by its ability to dephosphorylate the C‐terminal tyrosine residue (Y142) on the histone variant H2AX, a modification that decisively shifts the cellular response from apoptotic signaling to efficient DNA repair upon genotoxic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In developmental contexts, EYA3 functions as a cofactor—for example, through its synergistic interaction with Six1—to regulate gene expression programs involved in muscle differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and to activate thyroid-stimulating hormone β expression in the pars tuberalis, thereby contributing to photoperiodic and seasonal timekeeping."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the context of disease, aberrantly high levels of EYA3 have been linked to enhanced DNA repair and chemoresistance in cancers such as Ewing sarcoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and to the survival of pulmonary arterial smooth muscle cells under DNA-damaging conditions in pulmonary hypertension."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, EYA3 modulates oncogenic pathways by interacting with the PP2A-B55α holoenzyme, thereby promoting c-Myc stabilization"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and its own phosphorylation status—regulated by Src kinase—further influences cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Recent studies in vertebrate models also reveal that EYA3 plays a central role in reproductive physiology, with its expression in the pituitary correlating with seasonal breeding signals in both teleosts"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "and amphibians."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, the identification of a conserved threonine phosphatase domain within EYA3 suggests that, in addition to its tyrosine phosphatase activity, it may possess distinct regulatory functions"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and emerging evidence implicates EYA3 in oncogenic networks involving non-coding RNAs that modulate the EYA3/c-Myc axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight EYA3 as a pivotal regulator at the intersection of DNA repair, developmental signaling, and disease progression, underscoring its potential as a therapeutic target in conditions characterized by aberrant DNA damage responses and proliferative signaling.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peter J Cook, Bong Gun Ju, Francesca Telese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07849"}], "href": "https://doi.org/10.1038/nature07849"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19234442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19234442"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Navasona Krishnan, Dae Gwin Jeong, Suk-Kyeong Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C900032200"}], "href": "https://doi.org/10.1074/jbc.C900032200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19351884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19351884"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hong Zhang, Ed Stavnezer "}, {"type": "b", "children": [{"type": "t", "text": "Ski regulates muscle terminal differentiation by transcriptional activation of Myog in a complex with Six1 and Eya3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M807526200"}], "href": "https://doi.org/10.1074/jbc.M807526200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19008232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19008232"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Koh-Hei Masumoto, Maki Ukai-Tadenuma, Takeya Kasukawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acute induction of Eya3 by late-night light stimulation triggers TSHβ expression in photoperiodism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2010.11.038"}], "href": "https://doi.org/10.1016/j.cub.2010.11.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21129973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21129973"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuhua Wang, Ram Naresh Pandey, Kaushik Roychoudhury, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting EYA3 in Ewing Sarcoma Retards Tumor Growth and Angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-20-0749"}], "href": "https://doi.org/10.1158/1535-7163.MCT-20-0749"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33649104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33649104"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tyler P Robin, Anna Smith, Erin McKinsey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EWS/FLI1 regulates EYA3 in Ewing sarcoma via modulation of miRNA-708, resulting in increased cell survival and chemoresistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-12-0086"}], "href": "https://doi.org/10.1158/1541-7786.MCR-12-0086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22723308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22723308"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yuhua Wang, Ram Naresh Pandey, Allen J York, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The EYA3 tyrosine phosphatase activity promotes pulmonary vascular remodeling in pulmonary arterial hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-12226-1"}], "href": "https://doi.org/10.1038/s41467-019-12226-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31515519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31515519"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lingdi Zhang, Hengbo Zhou, Xueni Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03327-4"}], "href": "https://doi.org/10.1038/s41467-018-03327-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29535359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29535359"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Aura E Ionescu, Mihaela Mentel, Cristian V A Munteanu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of EYA3 Phosphorylation by Src Kinase Identifies Residues Involved in Cell Proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms20246307"}], "href": "https://doi.org/10.3390/ijms20246307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31847183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31847183"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "A Doyle, M E Cowan, H Migaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuroendocrine regulation of reproduction in Atlantic cod (Gadus morhua): Evidence of Eya3 as an integrator of photoperiodic cues and nutritional regulation to initiate sexual maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comp Biochem Physiol A Mol Integr Physiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cbpa.2021.111000"}], "href": "https://doi.org/10.1016/j.cbpa.2021.111000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34089890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34089890"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Bijoy Krishna Borah, Zothanmawii Renthlei, Amit Tripathi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular and epigenetic regulation of seasonal reproduction in Terai tree frog (Polypedates teraiensis)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Photochem Photobiol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s43630-022-00195-2"}], "href": "https://doi.org/10.1007/s43630-022-00195-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35262895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35262895"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Teruyuki Sano, Shigekazu Nagata "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the threonine-phosphatase of mouse eyes absent 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2011.07.029"}], "href": "https://doi.org/10.1016/j.febslet.2011.07.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21821028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21821028"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Shengxian Xu, Zhenpeng Lian, Siyang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircGNG4 Promotes the Progression of Prostate Cancer by Sponging miR-223 to Enhance EYA3/c-myc Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2021.684125"}], "href": "https://doi.org/10.3389/fcell.2021.684125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34395419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34395419"}]}]}]}
Proteins	EYA3_HUMAN
NCBI Gene ID	2140
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EYA3 has 6,325 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 121 datasets.

Click the + buttons to view associations for EYA3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EYA3 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 EYA3 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 EYA3 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 EYA3 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 EYA3 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 EYA3 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 EYA3 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 EYA3 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 EYA3 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 EYA3 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 EYA3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EYA3 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 EYA3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EYA3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EYA3 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 EYA3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EYA3 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 EYA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EYA3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EYA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EYA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EYA3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing EYA3 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 EYA3 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 EYA3 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 EYA3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EYA3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EYA3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EYA3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EYA3 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 EYA3 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 EYA3 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 EYA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EYA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at EYA3 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 EYA3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EYA3 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 EYA3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of EYA3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with EYA3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing EYA3 from the GeneSigDB Published Gene Signatures dataset.