{"entity":{"id":"gsk3b","kind":"target","name":"GSK3B","aka":["glycogen synthase kinase 3 beta","Glycogen synthase kinase-3 beta"],"tldr":"GSK3B (Glycogen synthase kinase-3 beta) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target and a tumour suppressor, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Gastric & gastro-oesophageal junction cancer.","summary":"Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signalling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis.\n\nOpen Targets scores its association with cancer at 0.67 (direct and indirect evidence; datatypes clinical 0.20, affected pathway 0.89, literature 1.00, genetic association 0.39, somatic mutation 0.44, animal model 0.58). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Stomach Adenocarcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:4617","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4617"},{"label":"UniProt P49841","url":"https://www.uniprot.org/uniprotkb/P49841/entry"},{"label":"NCBI Gene 2932","url":"https://www.ncbi.nlm.nih.gov/gene/2932"},{"label":"Ensembl ENSG00000082701","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000082701"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.20; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"GSK3B","role":["drug-target","tumour-suppressor"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:4617","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4617","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P49841","url":"https://www.uniprot.org/uniprotkb/P49841/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000082701","url":"https://platform.opentargets.org/target/ENSG00000082701/associations","note":"association with cancer (MONDO_0004992) 0.67;  (GraphQL API, CC0)"},{"label":"IntOGen GSK3B","url":"https://www.intogen.org/search?gene=GSK3B","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"one-type","specificityNote":"Tumour-specific alteration: the catalogues call it a tumour suppressor (IntOGen finds it knocked out more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA GSK3B: RNA low tissue specificity; high antibody staining in 4 normal tissues; highest cancer staining carcinoid (1 of 4 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Gastric & gastro-oesophageal junction cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P49841","url":"https://www.uniprot.org/uniprotkb/P49841/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"IntOGen GSK3B","url":"https://www.intogen.org/search?gene=GSK3B","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas GSK3B tissue","url":"https://www.proteinatlas.org/ENSG00000082701-GSK3B/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000082701 associations","url":"https://platform.opentargets.org/target/ENSG00000082701/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4617","ensembl":"ENSG00000082701","uniprot":"P49841","entrez":"2932","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Stambolic et al, Biochem. J, 1994, \"Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7980435/","biology":"Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signalling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signalling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Location: Cytoplasm; Nucleus; Cell membrane (UniProt). Locus 3q13.33 (HGNC).","whereFound":["Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (STAD)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/gsk3b/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"}]}}