MAP3K9 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase kinase kinase 9
Description	Enables molecular function activator activity and protein serine/threonine kinase activity. Involved in protein autophosphorylation. Predicted to be located in membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAP3K9 is a mitogen‐activated protein kinase kinase kinase that functions as an important upstream regulator of MAPK signaling cascades – including the ERK, p38, and JNK pathways – thereby modulating key cellular processes such as proliferation, apoptosis, migration, and epithelial–mesenchymal transition. In melanoma cells, inactivating mutations in MAP3K9 reduce downstream MAPK phosphorylation and contribute to chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In neuroblastoma, overexpression of miR‑34a is associated with reduced MAP3K9 mRNA and protein levels, suggesting that post‐transcriptional regulation of MAP3K9 may impact apoptotic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In human colon cancer stem cells, miR‑93 is predicted to target MAP3K9 among other regulators, linking its modulation to altered cellular proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In osteosarcoma stem cells, miR‑1247 has been implicated as a tumor suppressor by targeting MAP3K9, while in nucleus pulposus cells from intervertebral disc degeneration patients, miR‑15a overexpression downregulates MAP3K9, leading to decreased activation of the p38 and ERK MAPK pathways and altered cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the context of lung cancer, gain‐of‐function mutations in MAP3K9 have been identified that enhance ERK pathway signaling and support tumor cell viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Finally, in both esophageal squamous cell carcinoma and lung adenocarcinoma, downregulation or hypermethylation‐associated loss of miR‑148a (or its mature form miR‑148a‑3p) leads to increased MAP3K9 levels, which in turn drive tumor cell invasion and metastasis via the ERK/MAPK cascade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies reveal that MAP3K9 plays a multifunctional role in cancer by integrating diverse upstream regulatory signals – including those from oncogenic microRNAs – to modulate MAPK-driven responses. As such, MAP3K9 represents a promising therapeutic target, with its altered activity having significant implications for tumorigenesis, metastasis, and chemotherapeutic resistance.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mitchell S Stark, Susan L Woods, Michael G Gartside, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.1041"}], "href": "https://doi.org/10.1038/ng.1041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22197930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22197930"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Amanda Tivnan, Lorraine Tracey, Patrick G Buckley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-11-33"}], "href": "https://doi.org/10.1186/1471-2407-11-33"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21266077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21266077"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiao-Feng Yu, Jian Zou, Zhi-Jun Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-93 suppresses proliferation and colony formation of human colon cancer stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v17.i42.4711"}], "href": "https://doi.org/10.3748/wjg.v17.i42.4711"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22180714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22180714"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fuyou Zhao, Jie Lv, Huaiyong Gan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiRNA profile of osteosarcoma with CD117 and stro-1 expression: miR-1247 functions as an onco-miRNA by targeting MAP3K9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25973030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25973030"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ping Cai, Ting Yang, Xingjie Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of miR-15a in intervertebral disc degeneration through targeting MAP3K9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2016.12.128"}], "href": "https://doi.org/10.1016/j.biopha.2016.12.128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28081468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28081468"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shameem Fawdar, Eleanor W Trotter, Yaoyong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1305207110"}], "href": "https://doi.org/10.1073/pnas.1305207110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23836671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23836671"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "B-X Zhang, T Yu, Z Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201908_18533"}], "href": "https://doi.org/10.26355/eurrev_201908_18533"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31378889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31378889"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lu Liang, Wen-Yan Xu, Ao Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Pharmacol Sin (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41401-022-00893-8"}], "href": "https://doi.org/10.1038/s41401-022-00893-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35388129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35388129"}]}]}]}
Synonyms	MLK1, MEKK9, PRKE1
Proteins	M3K9_HUMAN
NCBI Gene ID	4293
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAP3K9 has 5,737 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 121 datasets.

Click the + buttons to view associations for MAP3K9 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAP3K9 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 MAP3K9 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 MAP3K9 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 MAP3K9 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 MAP3K9 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 MAP3K9 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 MAP3K9 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAP3K9 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP3K9 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 MAP3K9 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 MAP3K9 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP3K9 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 MAP3K9 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAP3K9 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAP3K9 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 MAP3K9 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAP3K9 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 MAP3K9 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 MAP3K9 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAP3K9 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 MAP3K9 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 MAP3K9 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 MAP3K9 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 MAP3K9 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAP3K9 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MAP3K9 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MAP3K9 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MAP3K9 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 MAP3K9 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MAP3K9 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with MAP3K9 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 MAP3K9 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 MAP3K9 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 MAP3K9 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAP3K9 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for MAP3K9 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MAP3K9 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 MAP3K9 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAP3K9 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 MAP3K9 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with MAP3K9 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.