MAP4K1 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase kinase kinase kinase 1
Description	Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Mitogen‐activated protein kinase kinase kinase kinase 1 (MAP4K1), also known as hematopoietic progenitor kinase 1 (HPK1), is a serine/threonine kinase that links extracellular and intracellular signals to both oncogenic and immunoregulatory pathways. In tumor cells, MAP4K1 functions as an upstream activator of the stress‐activated JNK cascade, leading to c‐Jun phosphorylation and consequent AP‐1–dependent transcription that promotes cancer cell invasion and progression. For instance, loss of the tumor suppressor PDCD4 results in increased MAP4K1 expression along with enhanced JNK and c‐Jun activity, thereby facilitating cellular invasion and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Additionally, aberrant expression of specific microRNAs – such as miR‐96 – upregulates MAP4K1 levels, contributing to oncogenic processes in bladder cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the immune compartment, MAP4K1 plays a pivotal negative regulatory role. High MAP4K1 expression in T cells is associated with T cell exhaustion and impaired effector functions, which can hinder effective anti‐tumor responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, regulatory proteins such as PDIA6 modulate MAP4K1 activity by impacting its phosphorylation status, thus influencing the downstream JNK/c‐Jun pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies position MAP4K1 as a critical bifunctional mediator: in tumor cells, it drives pro‐invasive signaling via the JNK/c‐Jun axis, while in immune cells, its elevated activity contributes to T cell dysfunction and immune evasion. This duality renders MAP4K1 an attractive therapeutic target for modulating both cancer cell aggressiveness and anti‐tumor immunity.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hsin-Sheng Yang, Connie P Matthews, Timothy Clair, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.4.1297-1306.2006"}], "href": "https://doi.org/10.1128/MCB.26.4.1297-1306.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16449643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16449643"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qing Wang, Yan Zhang, Hsin-Sheng Yang "}, {"type": "b", "children": [{"type": "t", "text": "Pdcd4 knockdown up-regulates MAP4K1 expression and activation of AP-1 dependent transcription through c-Myc."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2012.07.004"}], "href": "https://doi.org/10.1016/j.bbamcr.2012.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22801218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22801218"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yi Wang, Hongmei Luo, Yangle Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hsa-miR-96 up-regulates MAP4K1 and IRS1 and may function as a promising diagnostic marker in human bladder urothelial carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2011.621"}], "href": "https://doi.org/10.3892/mmr.2011.621"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21993544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21993544"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jingwen Si, Xiangjun Shi, Shuhao Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2020.08.001"}], "href": "https://doi.org/10.1016/j.ccell.2020.08.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32860752"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32860752"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuxin Bai, Xuefeng Liu, Xiaoyu Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDIA6 modulates apoptosis and autophagy of non-small cell lung cancer cells via the MAP4K1/JNK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2019.03.045"}], "href": "https://doi.org/10.1016/j.ebiom.2019.03.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30922965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30922965"}]}]}]}
Synonyms	HPK1
Proteins	M4K1_HUMAN
NCBI Gene ID	11184
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAP4K1 has 5,701 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 119 datasets.

Click the + buttons to view associations for MAP4K1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAP4K1 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 MAP4K1 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 MAP4K1 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 MAP4K1 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 MAP4K1 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 MAP4K1 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 MAP4K1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAP4K1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP4K1 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 MAP4K1 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 MAP4K1 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 MAP4K1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP4K1 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 MAP4K1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAP4K1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAP4K1 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 MAP4K1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAP4K1 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 MAP4K1 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 MAP4K1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAP4K1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAP4K1 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 MAP4K1 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 MAP4K1 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 MAP4K1 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 MAP4K1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAP4K1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MAP4K1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by MAP4K1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate MAP4K1 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MAP4K1 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 MAP4K1 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 MAP4K1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAP4K1 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 MAP4K1 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 MAP4K1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAP4K1 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 MAP4K1 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 MAP4K1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with MAP4K1 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 MAP4K1 from the GeneSigDB Published Gene Signatures dataset.