EYA4 Gene

HGNC Family	Phosphatases
Name	EYA transcriptional coactivator and phosphatase 4
Description	This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EYA4 is emerging as a multifunctional protein whose roles span from development and tissue homeostasis to the regulation of immune responses and tumor suppression. Mutations and deletions in EYA4 disrupt its function as a transcriptional co‐activator and phosphatase, leading to sensorineural hearing loss and, in some cases, dilated cardiomyopathy. In particular, loss‐of‐function alleles that truncate or alter the EYA4 protein compromise its interaction with SIX proteins and impair normal myocardial and auditory development (a detailed example is provided in."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its developmental importance, EYA4 contributes to innate immunity by stimulating the production of interferon‐β and CXCL10 in response to intracellular DNA damage—a function that depends on its threonine‐phosphatase activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Genetic variation in the EYA4 locus also appears clinically relevant; for example, specific alleles are associated with improved responsiveness to anti‐tumor necrosis factor therapy in rheumatoid arthritis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and with altered susceptibility to noise‐induced hearing loss."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the field of oncology, EYA4 frequently exhibits epigenetic silencing through promoter hypermethylation in several cancers, including colorectal, hepatocellular, and esophageal squamous cell carcinomas. Loss of EYA4 expression in these tumors is associated with enhanced oncogenic signaling—via pathways such as Wnt and NF‑κB/RAP1—and contributes to increased tumor cell proliferation, invasion, and migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": " Moreover, aberrant regulation of EYA4 also impacts cell adhesion and survival in malignant peripheral nerve sheath tumors, suggesting additional therapeutic avenues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the collected data underscore a central role for EYA4 in mediating transcriptional regulation through its phosphatase activity and protein interactions. Its normal function is essential for maintaining cardiac and auditory integrity, modulating innate immune defenses, and restraining oncogenic processes. Dysregulation of EYA4—whether by genetic mutation, altered splicing, or epigenetic suppression—can therefore contribute to a broad spectrum of human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jost Schönberger, Libin Wang, Jordan T Shin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1527"}], "href": "https://doi.org/10.1038/ng1527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15735644"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15735644"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Markus Pfister, Tímea Tóth, Holger Thiele, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A 4-bp insertion in the eya-homologous region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12477971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12477971"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tomoko Makishima, Anne C Madeo, Carmen C Brewer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.31793"}], "href": "https://doi.org/10.1002/ajmg.a.31793"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17567890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17567890"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michael S Hildebrand, David Coman, Tao Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel splice site mutation in EYA4 causes DFNA10 hearing loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.31860"}], "href": "https://doi.org/10.1002/ajmg.a.31860"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17568404"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17568404"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yasutaka Okabe, Teruyuki Sano, Shigekazu Nagata "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the innate immune response by threonine-phosphatase of Eyes absent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08138"}], "href": "https://doi.org/10.1038/nature08138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19561593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19561593"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Darren Plant, John Bowes, Catherine Potter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.30130"}], "href": "https://doi.org/10.1002/art.30130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21061259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21061259"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xuhui Zhang, Yi Liu, Lei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Associations of genetic variations in EYA4, GRHL2 and DFNA5 with noise-induced hearing loss in Chinese population: a case- control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Health (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12940-015-0063-2"}], "href": "https://doi.org/10.1186/s12940-015-0063-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26400775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26400775"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shi-Jing Mo, Xun Hou, Xiao-Yi Hao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EYA4 inhibits hepatocellular carcinoma growth and invasion by suppressing NF-κB-dependent RAP1 transactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Commun (Lond) (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40880-018-0276-1"}], "href": "https://doi.org/10.1186/s40880-018-0276-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29764501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29764501"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yanqun Liu, Chee Kian Tham, Simon Y K Ong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum methylation levels of TAC1. SEPT9 and EYA4 as diagnostic markers for early colorectal cancers: a pilot study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomarkers (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/1354750X.2013.798745"}], "href": "https://doi.org/10.3109/1354750X.2013.798745"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23862763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23862763"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sung-Jin Kim, Chung Hyun Tae, Sung Noh Hong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EYA4 Acts as a New Tumor Suppressor Gene in Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.22247"}], "href": "https://doi.org/10.1002/mc.22247"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25620232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25620232"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Mei Luo, Yuan Li, Xuejiao Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.13615"}], "href": "https://doi.org/10.1111/cas.13615"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29660222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29660222"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yi A Ren, Lisa K Mullany, Zhilin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant p53 Promotes Epithelial Ovarian Cancer by Regulating Tumor Differentiation, Metastasis, and Responsiveness to Steroid Hormones."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-15-1046"}], "href": "https://doi.org/10.1158/0008-5472.CAN-15-1046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26964623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26964623"}]}]}]}
Synonyms	DFNA10, CMD1J
Proteins	EYA4_HUMAN
NCBI Gene ID	2070
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EYA4 has 5,635 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for EYA4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EYA4 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 EYA4 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 EYA4 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 EYA4 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 EYA4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of EYA4 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 EYA4 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 EYA4 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 EYA4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EYA4 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 EYA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EYA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EYA4 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 EYA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with EYA4 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EYA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EYA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EYA4 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 EYA4 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 EYA4 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 EYA4 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 EYA4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EYA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EYA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EYA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with EYA4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EYA4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving EYA4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving EYA4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with EYA4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EYA4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with EYA4 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 EYA4 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 EYA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EYA4 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 EYA4 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 EYA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EYA4 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 EYA4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with EYA4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with EYA4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.