GSK3B Gene

Name	glycogen synthase kinase 3 beta
Description	The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine kinase that serves as a nodal regulator integrating signals from pathways such as PI3K/Akt, MAPK, and Wnt to influence cell fate in diverse biological contexts. In some settings, GSK3β phosphorylates substrates to promote their ubiquitin‐mediated degradation—for example, it mediates phosphorylation‐dependent proteasomal turnover of PD-L1, thereby modulating tumor-associated immune escape."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cardiac tissue, upstream inactivation of GSK3β by Akt is critical for permitting nuclear translocation of Nrf2 and consequent activation of mitochondrial biogenesis programs that protect against cardiomyocyte apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, during heart development, signals that lead to GSK3β inactivation via the IGF pathway contribute to increased β-catenin stability and promote cardiomyocyte proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In other cellular contexts, GSK3β phosphorylates the transcription factor Nrf2, thereby restricting its nuclear residence and diminishing antioxidant phase II gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, GSK3β activity can be modulated by alternative upstream kinases such as p38 MAPK, with such phosphorylation events contributing to β-catenin accumulation and influencing cell survival mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the nervous system, aberrant activity of GSK3β is implicated in the pathogenesis of Alzheimer’s disease, where it phosphorylates tau protein, thereby promoting neurofibrillary tangle formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the heart, regulation of GSK3β by Akt and its subsequent effects on β-catenin and downstream transcription factors underscores its importance in hypertrophic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, in colorectal cancer, persistent and active GSK3β supports tumor cell survival and proliferation, as evidenced by experiments in which its inhibition induced apoptosis and attenuated cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these studies highlight the context-dependent and multifaceted roles of GSK3β in modulating protein stability, transcriptional programs, and cell survival across a spectrum of physiological and pathological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chia-Wei Li, Seung-Oe Lim, Weiya Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms12632"}], "href": "https://doi.org/10.1038/ncomms12632"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27572267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27572267"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Claude A Piantadosi, Martha Sue Carraway, Abdelwahid Babiker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.RES.0000338597.71702.ad"}], "href": "https://doi.org/10.1161/01.RES.0000338597.71702.ad"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18845810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18845810"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mei Xin, Yuri Kim, Lillian B Sutherland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2002278"}], "href": "https://doi.org/10.1126/scisignal.2002278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22028467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22028467"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "María Salazar, Ana I Rojo, Diego Velasco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycogen synthase kinase-3beta inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M513737200"}], "href": "https://doi.org/10.1074/jbc.M513737200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16551619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16551619"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tina M Thornton, Gustavo Pedraza-Alva, Bin Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1156037"}], "href": "https://doi.org/10.1126/science.1156037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18451303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18451303"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hideki Shimura, Daniel Schwartz, Steven P Gygi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival."}]}, {"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.M305838200"}], "href": "https://doi.org/10.1074/jbc.M305838200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14612456"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14612456"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gianluigi Condorelli, Alessandra Drusco, Giorgio Stassi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.172376399"}], "href": "https://doi.org/10.1073/pnas.172376399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12237475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12237475"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Abbas Shakoori, Andrei Ougolkov, Zhi Wei Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deregulated GSK3beta activity in colorectal cancer: its association with tumor cell survival and proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.07.041"}], "href": "https://doi.org/10.1016/j.bbrc.2005.07.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16043125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16043125"}]}]}]}
Proteins	GSK3B_HUMAN
NCBI Gene ID	2932
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GSK3B has 26,120 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 149 datasets.

Click the + buttons to view associations for GSK3B from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GSK3B 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 GSK3B 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 GSK3B 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 GSK3B 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 GSK3B 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 GSK3B 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 GSK3B 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 GSK3B gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving GSK3B protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of GSK3B 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 GSK3B 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 GSK3B 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 GSK3B gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GSK3B 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 GSK3B gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with GSK3B gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GSK3B protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GSK3B 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 GSK3B gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GSK3B 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 GSK3B 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 GSK3B gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of GSK3B gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing GSK3B protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GSK3B gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GSK3B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GSK3B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing GSK3B 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 GSK3B 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 GSK3B protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing GSK3B protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GSK3B gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GSK3B gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GSK3B gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GSK3B gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate GSK3B protein from the curated DEPOD Substrates of Phosphatases dataset.
	DGIdb Drug Targets 2026	interacting drugs for GSK3B protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving GSK3B gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving GSK3B gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GSK3B 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 GSK3B gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.