DUSP9 Gene

HGNC Family	Phosphatases
Name	dual specificity phosphatase 9
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 is 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 shows selectivity for members of the ERK family of MAP kinases and is localized to the cytoplasm and nucleus. Aberrant expression of this gene is associated with type 2 diabetes and cancer progression in several cell types. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dual‐specificity phosphatase 9 (DUSP9), also known as MKP‑4, is emerging as an important regulator at the crossroads of MAP kinase signaling, epigenetic modulation, and metabolic homeostasis. Genome‐wide association studies have identified the X‐chromosomal DUSP9 locus as a risk factor for type 2 diabetes in diverse populations, suggesting that altered DUSP9 expression can impact beta‐cell function and insulin action."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In human pancreatic islets, epigenetic studies have revealed sex‐specific differences in DNA methylation at the DUSP9 locus that correlate with differences in insulin secretion and the metabolic phenotype"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", a finding further supported by observations in pluripotent stem cells where DUSP9 contributes to female‐specific hypomethylation patterns."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in metabolism, genetic deletion experiments in mice have demonstrated that DUSP9 is indispensable for placental labyrinth development, as loss of DUSP9 in extraembryonic tissues leads to embryonic lethality—a defect that can be rescued by correcting placental function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " At the molecular level, DUSP9 functions as a dual‐specificity phosphatase capable of dephosphorylating key MAP kinases such as ERK1/2 and p38α. Moreover, its phosphatase activity is subject to regulation by post‐translational modifications; for instance, phosphorylation by protein kinase A attenuates the binding of DUSP9 to its substrates, thereby modulating MAPK signaling output."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight DUSP9 as a multifaceted molecule that not only governs MAPK signaling cascades but also influences epigenetic states and metabolic processes. Its critical functions in placental development and association with type 2 diabetes underscore the potential of DUSP9 as an attractive target for therapeutic intervention in metabolic and developmental disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.609"}], "href": "https://doi.org/10.1038/ng.609"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20581827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20581827"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Huaixing Li, Wei Gan, Ling Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db12-0454"}], "href": "https://doi.org/10.2337/db12-0454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22961080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22961080"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hisashi Fukuda, Minako Imamura, Yasushi Tanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0046263"}], "href": "https://doi.org/10.1371/journal.pone.0046263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23029454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23029454"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Elin Hall, Petr Volkov, Tasnim Dayeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13059-014-0522-z"}], "href": "https://doi.org/10.1186/s13059-014-0522-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25517766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25517766"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jiho Choi, Kendell Clement, Aaron J Huebner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2017.03.002"}], "href": "https://doi.org/10.1016/j.stem.2017.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28366588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28366588"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Graham R Christie, David J Williams, Fiona Macisaac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The dual-specificity protein phosphatase DUSP9/MKP-4 is essential for placental function but is not required for normal embryonic development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.18.8323-8333.2005"}], "href": "https://doi.org/10.1128/MCB.25.18.8323-8333.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16135819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16135819"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Robin J Dickinson, Laurent Delavaine, Rocío Cejudo-Marín, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of the kinase interaction motif in mitogen-activated protein (MAP) kinase phosphatase-4 mediates cross-talk between protein kinase A and MAP kinase signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.255844"}], "href": "https://doi.org/10.1074/jbc.M111.255844"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21908610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21908610"}]}]}]}
Synonyms	MKP4, MKP-4
Proteins	DUS9_HUMAN
NCBI Gene ID	1852
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DUSP9 has 5,631 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 114 datasets.

Click the + buttons to view associations for DUSP9 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DUSP9 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 DUSP9 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 DUSP9 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 DUSP9 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 DUSP9 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 DUSP9 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 DUSP9 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving DUSP9 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of DUSP9 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 DUSP9 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of DUSP9 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DUSP9 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 DUSP9 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DUSP9 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 DUSP9 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DUSP9 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 DUSP9 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 DUSP9 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 DUSP9 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DUSP9 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DUSP9 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 DUSP9 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 DUSP9 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DUSP9 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DUSP9 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DUSP9 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DUSP9 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 DUSP9 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with DUSP9 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DUSP9 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 DUSP9 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 DUSP9 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DUSP9 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 DUSP9 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 DUSP9 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DUSP9 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 DUSP9 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DUSP9 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with DUSP9 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 DUSP9 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DUSP9 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.