MAP3K1 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Description	The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAP3K1—a mitogen‐activated protein kinase kinase kinase also known as MEKK1—functions as an integral signaling node that modulates multiple cellular processes in a highly context‐dependent manner. Genetic studies have consistently implicated MAP3K1 variants in predisposition to cancers, such as breast cancer, while mutations in this gene are also causally associated with disorders of sex development in 46,XY individuals"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the signaling level, MAP3K1 acts upstream in the mitogen‐activated protein kinase cascades to coordinate cellular responses. In fibroblasts, for example, MAP3K1 regulates the balance between the Ras/MEK/ERK and JNK pathways to fine‐tune transforming growth factor–β (TGF‐β)–mediated induction of connective tissue growth factor, thereby influencing cell type–specific gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In gut epithelial cells, MAP3K1 is activated by interleukin–1β and is essential for triggering the canonical nuclear factor–κB (NF–κB) pathway that modulates tight junction permeability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, in cancer cells MAP3K1 exerts dual roles depending on the cellular context. In lung cancer cells, constitutive MAP3K1 activity can suppress mitogenic signals mediated by transcription factors such as TR3, while activation of MAP3K1 has also been shown to promote phosphorylation‐dependent nuclear export of the proapoptotic receptor Nur77, thereby facilitating apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, MAP3K1 is embedded within epidermal differentiation signaling networks that regulate involucrin gene expression—a key marker of keratinocyte differentiation—thus highlighting its role in tissue homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence indicates that MAP3K1 is subject to post‐transcriptional regulation; for instance, its expression is modulated by tumor–suppressive microRNAs such as miR–23b, which can influence metastasis by targeting MAP3K1 among other prometastatic genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these studies underscore that MAP3K1 is a multifunctional kinase whose activity governs critical decisions in cell survival, apoptosis, differentiation, and developmental processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gilles Thomas, Kevin B Jacobs, Peter Kraft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.353"}], "href": "https://doi.org/10.1038/ng.353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19330030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19330030"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Montserrat Garcia-Closas, Per Hall, Heli Nevanlinna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1000054"}], "href": "https://doi.org/10.1371/journal.pgen.1000054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18437204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18437204"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Antonis C Antoniou, Jonathan Beesley, Lesley McGuffog, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-10-1907"}], "href": "https://doi.org/10.1158/0008-5472.CAN-10-1907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21118973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21118973"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alexander Pearlman, Johnny Loke, Cedric Le Caignec, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.11.003"}], "href": "https://doi.org/10.1016/j.ajhg.2010.11.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21129722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21129722"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Andrew Leask, Alan Holmes, Carol M Black, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M210366200"}], "href": "https://doi.org/10.1074/jbc.M210366200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12571253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12571253"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rana Al-Sadi, Dongmei Ye, Hamid M Said, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-1beta-induced increase in intestinal epithelial tight junction permeability is mediated by MEKK-1 activation of canonical NF-kappaB pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2010.100371"}], "href": "https://doi.org/10.2353/ajpath.2010.100371"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21048223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21048223"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Siva Kumar Kolluri, Nathalie Bruey-Sedano, Xihua Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitogenic effect of orphan receptor TR3 and its regulation by MEKK1 in lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.23.8651-8667.2003"}], "href": "https://doi.org/10.1128/MCB.23.23.8651-8667.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14612408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14612408"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Y-H Han, X Cao, B Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209358"}], "href": "https://doi.org/10.1038/sj.onc.1209358"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16434970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16434970"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Richard L Eckert, James F Crish, Tatiana Efimova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of involucrin gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.0022-202X.2004.22723.x"}], "href": "https://doi.org/10.1111/j.0022-202X.2004.22723.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15191537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15191537"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hanshuo Zhang, Yang Hao, Junyu Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms1555"}], "href": "https://doi.org/10.1038/ncomms1555"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22109528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22109528"}]}]}]}
Synonyms	MEKK, MAPKKK1, MEKK 1, MEKK1, SRXY6
Proteins	M3K1_HUMAN
NCBI Gene ID	4214
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAP3K1 has 10,428 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 142 datasets.

Click the + buttons to view associations for MAP3K1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAP3K1 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 MAP3K1 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 MAP3K1 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 MAP3K1 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 MAP3K1 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 RNA-seq	tissue samples with high or low expression of MAP3K1 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 MAP3K1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAP3K1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP3K1 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 MAP3K1 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 MAP3K1 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 MAP3K1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP3K1 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 MAP3K1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAP3K1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAP3K1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAP3K1 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 MAP3K1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAP3K1 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 MAP3K1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MAP3K1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MAP3K1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAP3K1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MAP3K1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAP3K1 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 MAP3K1 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 MAP3K1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing MAP3K1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP3K1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAP3K1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAP3K1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAP3K1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MAP3K1 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 MAP3K1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving MAP3K1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MAP3K1 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 MAP3K1 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 MAP3K1 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 MAP3K1 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 MAP3K1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAP3K1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.