MAPK4 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase 4
Description	Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAPK4 is an atypical mitogen‐activated protein kinase that has emerged as an important regulator of oncogenic signaling and cell motility. Its function extends to directly phosphorylating downstream effectors—most notably, the MAPK‐activated protein kinase MK5—and modulating actin dynamics to influence tumor cell migration. In tumor‐derived cells, IGF2BP1 has been shown to control the cytoplasmic fate of MAPK4 mRNA, with inhibition of its translation leading to reduced MK5 activation and subsequent changes in actin monomer availability that enhance both migration velocity and directionality."}, {"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, MAPK4 has been implicated as a driver of oncogenic signaling by promoting AKT activation through a noncanonical mechanism. It directly phosphorylates AKT at threonine 308 and concurrently stimulates mTORC2-mediated phosphorylation at serine 473, thereby fostering cell survival, proliferation, and resistance to therapy independent of the classical PI3K pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The oncogenic roles of MAPK4 have been further underscored in cancers such as triple‐negative breast cancer and prostate cancer, where its elevated expression correlates with poor clinical outcomes. In these contexts, MAPK4 not only drives aberrant AKT signaling but also appears to support androgen receptor activation via enhanced expression and stabilization of key transcriptional regulators, contributing to castration resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight the multifaceted role of MAPK4 in regulating signal transduction pathways that enhance cancer cell migration, survival, and proliferation, thereby representing a promising biomarker and therapeutic target in diverse malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nadine Stöhr, Marcel Köhn, Marcell Lederer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.177642.111"}], "href": "https://doi.org/10.1101/gad.177642.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22279049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22279049"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shashi Kant, Stefanie Schumacher, Manvendra Kumar Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M606693200"}], "href": "https://doi.org/10.1074/jbc.M606693200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16973613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16973613"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tao Shen, Wei Wang, Wolong Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI135465"}], "href": "https://doi.org/10.1172/JCI135465"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33586682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33586682"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wei Wang, Dong Han, Qinbo Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-27921-1"}], "href": "https://doi.org/10.1038/s41467-021-27921-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35017531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35017531"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wei Wang, Tao Shen, Bingning Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI97712"}], "href": "https://doi.org/10.1172/JCI97712"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30688659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30688659"}]}]}]}
Synonyms	P63MAPK, ERK4, P63-MAPK, PRKM4, ERK-4
Proteins	MK04_HUMAN
NCBI Gene ID	5596
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAPK4 has 5,274 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 113 datasets.

Click the + buttons to view associations for MAPK4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAPK4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by MAPK4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAPK4 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 MAPK4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAPK4 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAPK4 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 MAPK4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAPK4 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 MAPK4 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 MAPK4 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 MAPK4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAPK4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MAPK4 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 MAPK4 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 MAPK4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAPK4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAPK4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAPK4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by MAPK4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for MAPK4 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MAPK4 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 MAPK4 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 MAPK4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAPK4 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 MAPK4 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 MAPK4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAPK4 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 MAPK4 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 MAPK4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with MAPK4 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 MAPK4 from the GeneSigDB Published Gene Signatures dataset.