STK3 Gene

Name	serine/threonine kinase 3
Description	This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSerine/threonine kinase 3 (STK3), also known as MST2, plays a pivotal role in regulating apoptosis. In renal cell carcinoma models, for example, the apoptogenic factor AIF was found to interact with STK3 and enhance its phosphorylation at Thr180, suggesting that STK3’s activation is important for caspase‐independent programmed cell death and proper maintenance of apoptotic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn melanoma, STK3 (MST2) functions as an important node of cross‐talk between the Hippo and MAPK pathways. Immunoprecipitation studies demonstrated that the serine/threonine kinase RAF-1 directly binds to STK3, intimating that although RAF-1 knockdown did not alter STK3 levels, this interaction modulates the downstream effectors YAP and TAZ. This interrelationship emphasizes that STK3 is embedded within a complex network of growth-regulatory signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn ovarian cancer, STK3 appears to manifest its canonical tumor-suppressive role. Analyses revealed that STK3 is significantly downregulated in ovarian cancer patients, with low expression correlating with poor prognosis. Functional studies showed that forced expression of STK3 inhibited cell proliferation, migration, and tumor growth in vivo while promoting CD8⁺ T-cell chemotaxis via activation of NF-κB signaling. These findings identify STK3 as both a potential prognostic marker and a mediator of anti-tumor immunity in this context."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nContrastingly, in prostate cancer, STK3 adopts a non-canonical, pro-tumorigenic role. Here, STK3 is frequently amplified, and its high expression is associated with decreased overall survival and increased androgen receptor activity. In prostate cancer models, pharmacological inhibition and genetic depletion of STK3 markedly reduced cell proliferation, spheroid growth, and invasion—findings that position STK3 as a potential therapeutic target despite its classical function as a Hippo pathway kinase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shengqiang Xu, Hongjin Wu, Huan Nie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AIF downregulation and its interaction with STK3 in renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0100824"}], "href": "https://doi.org/10.1371/journal.pone.0100824"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24992339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24992339"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ruizheng Feng, Junsheng Gong, Lina Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAPK and Hippo signaling pathways crosstalk via the RAF-1/MST-2 interaction in malignant melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2017.5774"}], "href": "https://doi.org/10.3892/or.2017.5774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28677804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28677804"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiangyu Wang, Fengmian Wang, Zhi-Gang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STK3 Suppresses Ovarian Cancer Progression by Activating NF-"}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "κ"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "B Signaling to Recruit CD8"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " T-Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2020/7263602"}], "href": "https://doi.org/10.1155/2020/7263602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33062724"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33062724"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Amelia U Schirmer, Lucy M Driver, Megan T Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2021.08.029"}], "href": "https://doi.org/10.1016/j.ymthe.2021.08.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34450249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34450249"}]}]}]}
Synonyms	KRS1, MST2
Proteins	STK3_HUMAN
NCBI Gene ID	6788
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

STK3 has 6,780 functional associations with biological entities spanning 8 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) extracted from 116 datasets.

Click the + buttons to view associations for STK3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

STK3 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 STK3 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 STK3 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 STK3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of STK3 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 STK3 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 STK3 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 STK3 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 STK3 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 STK3 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 STK3 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 STK3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with STK3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with STK3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with STK3 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 STK3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of STK3 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 STK3 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 STK3 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 STK3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing STK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with STK3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of STK3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with STK3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with STK3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with STK3 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 STK3 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 STK3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate STK3 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DGIdb Drug Targets 2026	interacting drugs for STK3 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with STK3 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 STK3 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 STK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with STK3 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 STK3 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 STK3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of STK3 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 STK3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with STK3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with STK3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of STK3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.