DUSP4 Gene

HGNC Family	Phosphatases
Name	dual specificity phosphatase 4
Description	The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DUSP4 is a dual‐specificity phosphatase that plays a critical role as a negative regulator of mitogen‐activated protein kinase (MAPK) signaling, with important implications in cancer and immunity. In lung adenocarcinoma, DUSP4 is involved in the negative feedback control of epidermal growth factor receptor (EGFR) signaling, and its underexpression is functionally linked to oncogenic EGFR mutations and a corresponding growth‐suppressor role ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. In basal‐like breast cancers, a deficiency in DUSP4 leads to aberrant MAPK pathway activation that contributes to resistance against taxane-induced apoptosis and promotes cancer stem cell–like behavior ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "]. In the context of immune regulation, increased DUSP4 transcription in activated CD4⁺ T cells from elderly individuals shortens the expression duration of key costimulatory molecules and cytokines—impairing T cell help and thereby the overall adaptive immune response ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]. Moreover, in gastric cancer cells, targeting of DUSP4 by miR-122-5p modulates cell migration and invasiveness, with downregulation of DUSP4 leading to restrained metastatic capabilities ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]. Finally, dual inactivation of DUSP4 along with its paralog DUSP6 in NRAS- and BRAF-mutant cancer cells results in hyperactivation of MAPK signaling, unveiling a digenic vulnerability that may be exploited for therapeutic gain ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the context-dependent roles of DUSP4 – from its tumor suppressor function via curtailing excessive MAPK activity in epithelial cancers, to modulating immune cell activation – and highlight its potential as a therapeutic target across a spectrum of human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "D Chitale, Y Gong, B S Taylor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.135"}], "href": "https://doi.org/10.1038/onc.2009.135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19525976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19525976"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Justin M Balko, Luis J Schwarz, Neil E Bhola, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-13-1385"}], "href": "https://doi.org/10.1158/0008-5472.CAN-13-1385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23966295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23966295"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mingcan Yu, Guangjin Li, Won-Woo Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1109797109"}], "href": "https://doi.org/10.1073/pnas.1109797109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22434910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22434910"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaofeng Xu, Feng Gao, Jianjiang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384047.2018.1423925"}], "href": "https://doi.org/10.1080/15384047.2018.1423925"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29509059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29509059"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Takahiro Ito, Michael J Young, Ruitong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-021-00967-z"}], "href": "https://doi.org/10.1038/s41588-021-00967-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34857952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34857952"}]}]}]}
Synonyms	HVH2, MKP2, TYP, MKP-2
Proteins	DUS4_HUMAN
NCBI Gene ID	1846
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DUSP4 has 14,490 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 119 datasets.

Click the + buttons to view associations for DUSP4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DUSP4 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 DUSP4 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 DUSP4 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 DUSP4 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 DUSP4 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 DUSP4 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 DUSP4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving DUSP4 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of DUSP4 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 DUSP4 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 DUSP4 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 DUSP4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DUSP4 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 DUSP4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DUSP4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DUSP4 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 DUSP4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DUSP4 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 DUSP4 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 DUSP4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DUSP4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DUSP4 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 DUSP4 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 DUSP4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DUSP4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DUSP4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DUSP4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DUSP4 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 DUSP4 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 DUSP4 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 DUSP4 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 DUSP4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DUSP4 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 DUSP4 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 DUSP4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DUSP4 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 DUSP4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with DUSP4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of DUSP4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DUSP4 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 DUSP4 from the GeneSigDB Published Gene Signatures dataset.