MAPK12 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase 12
Description	Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMAPK12 (p38γ) plays multifaceted roles in normal physiology. In skeletal muscle, it is predominantly expressed where its activation increases basal glucose uptake while concomitantly reducing the insulin‐independent, stimulated uptake by modulating GLUT4 levels, thereby contributing to cellular energy balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In hepatocytes, p38γ functions in a CDK‐like manner to phosphorylate the retinoblastoma protein, promoting the G0‐to‐G1 cell cycle transition and facilitating liver regeneration, while it also participates in oncogene‐induced senescence via phosphorylation of p53."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Tissue distribution studies have revealed high levels of p38γ expression in the heart and skeletal muscle, supporting its tissue‐specific roles"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and compensatory upregulation of p38γ is observed when p38α/β activities are pharmacologically inhibited during differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Further, studies employing intrinsically active p38γ mutants have uncovered its distinct capacity to regulate transcription factor activity, and its requirement for proper mitotic progression and cell viability has been demonstrated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn oncogenic contexts, MAPK12 exerts a strong pro‐tumorigenic influence. Its PDZ-binding motif enables cooperation with protein phosphatases such as PTPH1 to potentiate Ras-dependent transformation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while p38γ-mediated p53 phosphorylation is implicated in the senescence response that can act as a barrier to tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Aberrant p38γ expression has been further linked to enhanced metastatic and proliferative properties in breast and colorectal cancers by upregulating RhoC and driving cell cycle regulators, notably through increased Rb phosphorylation and cyclin E1/A expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " This oncogenic potential extends to diverse malignancies: in nasopharyngeal and esophageal squamous cell carcinomas as well as in colorectal tumors, overexpression of p38γ correlates with aggressive clinicopathological features and heightened tumor cell viability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in metabolism and tumor cell proliferation, MAPK12 is a key mediator of stress and therapeutic responses. In cancer cells treated with topoisomerase II inhibitors, p38γ is selectively activated to phosphorylate and stabilize Topo IIα, thereby enhancing drug efficacy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " In estrogen receptor–positive breast cancer, p38γ activation by tamoxifen leads to phosphorylation of ER at Ser-118 and a shift from classical to nonclassical transcriptional regulation, impacting hormone sensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Reciprocal regulatory interactions further underscore its signaling versatility; p38γ directly phosphorylates its specific phosphatase partners—PTPH1 and PTPN4—to modulate downstream pro-oncogenic and apoptotic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " In the context of immune cells, p38γ contributes to apoptosis of T cells during viral infections, while in laryngeal carcinogenesis exosomal lncRNAs have been shown to upregulate p38γ expression, further linking it to cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " Moreover, metabolomic analyses in breast cancer underscore the emerging promise of p38γ both as a biomarker and as a therapeutic target"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ", and its activation in response to DNA damage via MRK further broadens its role in cellular checkpoint regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richard C Ho, Oscar Alcazar, Nobuharu Fujii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p38gamma MAPK regulation of glucose transporter expression and glucose uptake in L6 myotubes and mouse skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Regul Integr Comp Physiol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpregu.00563.2003"}], "href": "https://doi.org/10.1152/ajpregu.00563.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14592936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14592936"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Antonia Tomás-Loba, Elisa Manieri, Bárbara González-Terán, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p38γ is essential for cell cycle progression and liver tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-019-1112-8"}], "href": "https://doi.org/10.1038/s41586-019-1112-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30971822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30971822"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jinny Kwong, Lixin Hong, Rong Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p38alpha and p38gamma mediate oncogenic ras-induced senescence through differential mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M808327200"}], "href": "https://doi.org/10.1074/jbc.M808327200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19251701"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19251701"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Naomi W Court, Cristobal G dos Remedios, Jacky Cordell, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Hyperactive variants of p38alpha induce, whereas hyperactive variants of p38gamma suppress, activating protein 1-mediated transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M608012200"}], "href": "https://doi.org/10.1074/jbc.M608012200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17088247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17088247"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anu Kukkonen-Macchi, Oana Sicora, Katarzyna Kaczynska, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation and stabilization of topoisomerase IIα protein by p38γ mitogen-activated protein kinase sensitize breast cancer cells to its poisons."}]}, {"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.M111.229260"}], "href": "https://doi.org/10.1074/jbc.M111.229260"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21878638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21878638"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Xiaomei Qi, Huiying Zhi, Adrienne Lepp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p38γ mitogen-activated protein kinase (MAPK) confers breast cancer hormone sensitivity by switching estrogen receptor (ER) signaling from classical to nonclassical pathway via stimulating ER phosphorylation and c-Jun transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.349357"}], "href": "https://doi.org/10.1074/jbc.M112.349357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22399296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22399296"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Songwang Hou, Padmanaban S Suresh, Xiaomei Qi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Impact of p38γ mitogen-activated protein kinase (MAPK) on MDA-MB-231 breast cancer cells using metabolomic approach."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2018.11.002"}], "href": "https://doi.org/10.1016/j.biocel.2018.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30447427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30447427"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Elena Tosti, Linda Waldbaum, Gregg Warshaw, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M409961200"}], "href": "https://doi.org/10.1074/jbc.M409961200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15342622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15342622"}]}]}]}
Synonyms	SAPK-3, P38GAMMA, ERK-6, ERK6, PRKM12, SAPK3, MAPK 12
Proteins	MK12_HUMAN
NCBI Gene ID	6300
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAPK12 has 6,993 functional associations with biological entities spanning 9 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, sequence feature) extracted from 120 datasets.

Click the + buttons to view associations for MAPK12 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAPK12 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 MAPK12 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 MAPK12 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 MAPK12 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 MAPK12 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 MAPK12 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 MAPK12 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAPK12 protein from the Biocarta Pathways dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MAPK12 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 MAPK12 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAPK12 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 MAPK12 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAPK12 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAPK12 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAPK12 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 MAPK12 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAPK12 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 MAPK12 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 MAPK12 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAPK12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MAPK12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAPK12 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MAPK12 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 MAPK12 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 MAPK12 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAPK12 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAPK12 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAPK12 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MAPK12 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 MAPK12 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate MAPK12 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with MAPK12 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 MAPK12 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 MAPK12 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 MAPK12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAPK12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for MAPK12 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MAPK12 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 MAPK12 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAPK12 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 MAPK12 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.