ETV4 Gene

HGNC Family	Helix-turn-helix ETS type domain containing
Name	ets variant 4
Description	Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of keratinocyte differentiation and positive regulation of transcription by RNA polymerase II. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ETV4, a member of the PEA3 subfamily of ETS transcription factors, has emerged as a multifunctional regulator with key roles in both normal development and cancer. In prostate cancer, recurrent gene fusions—involving, for example, TMPRSS2 and ETV4—define distinct molecular subtypes that drive neoplastic transformation by deregulating transcriptional programs essential for cell proliferation and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Post‐translational regulation of ETV4 is also critical; under normal conditions, the ubiquitin ligase COP1 targets ETV4 (along with related family members ETV1 and ETV5) for degradation, whereas disruption of this pathway in prostate cancer results in enhanced stability and oncogenic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Elevated ETV4 expression is furthermore a prominent feature of certain round cell sarcomas harboring CIC–DUX4 fusions, where its upregulation contributes to a distinct transcriptional signature that helps to differentiate these tumors from other sarcoma subtypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In developmental contexts, ETV4 plays an essential role in organogenesis. Acting downstream of Ret signaling in the ureteric bud, ETV4—as well as its paralog ETV5—regulates key target genes (including Cxcr4, Myb, Met, and Mmp14) to promote proper renal branching morphogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, ETV4 contributes to the regulation of invasive programs in breast cancer by partnering with transcriptional coactivators (such as AIB1) to enhance matrix metalloproteinase expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Collectively, these studies underscore the dual nature of ETV4 as both a critical developmental regulator and an oncogenic driver whose deregulation perturbs normal cellular differentiation and promotes tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Scott A Tomlins, Rohit Mehra, Daniel R Rhodes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-06-0168"}], "href": "https://doi.org/10.1158/0008-5472.CAN-06-0168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16585160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16585160"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jeremy P Clark, Colin S Cooper "}, {"type": "b", "children": [{"type": "t", "text": "ETS gene fusions in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Urol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrurol.2009.127"}], "href": "https://doi.org/10.1038/nrurol.2009.127"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19657377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19657377"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alberto C Vitari, Kevin G Leong, Kim Newton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COP1 is a tumour suppressor that causes degradation of ETS transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10005"}], "href": "https://doi.org/10.1038/nature10005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21572435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21572435"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Katja Specht, Yun-Shao Sung, Lei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct transcriptional signature and immunoprofile of CIC-DUX4 fusion-positive round cell tumors compared to EWSR1-rearranged Ewing sarcomas: further evidence toward distinct pathologic entities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.22172"}], "href": "https://doi.org/10.1002/gcc.22172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24723486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24723486"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Benson C Lu, Cristina Cebrian, Xuan Chi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.476"}], "href": "https://doi.org/10.1038/ng.476"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19898483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19898483"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Li Qin, Lan Liao, Aisling Redmond, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00579-08"}], "href": "https://doi.org/10.1128/MCB.00579-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18644862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18644862"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sangphil Oh, Sook Shin, Ralf Janknecht "}, {"type": "b", "children": [{"type": "t", "text": "ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbcan.2012.02.002"}], "href": "https://doi.org/10.1016/j.bbcan.2012.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22425584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22425584"}]}]}]}
Synonyms	E1AF, E1A-F, PEA3, PEAS3
Proteins	ETV4_HUMAN
NCBI Gene ID	2118
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ETV4 has 8,533 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 116 datasets.

Click the + buttons to view associations for ETV4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ETV4 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 ETV4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with ETV4 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ETV4 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 ETV4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ETV4 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 ETV4 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 ETV4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ETV4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ETV4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ETV4 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 ETV4 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 ETV4 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 ETV4 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 ETV4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ETV4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ETV4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ETV4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ETV4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ETV4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ETV4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ETV4 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 ETV4 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 ETV4 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 ETV4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ETV4 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 ETV4 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 ETV4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ETV4 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 ETV4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.