GSK3B
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.
Overview
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.
Open 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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at GSK3B yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:4617 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P49841 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000082701 (association with cancer (MONDO_0004992) 0.67; (GraphQL API, CC0)); IntOGen GSK3B (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (STAD)
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"GSK3B" OR ABSTRACT:"GSK3B" OR TITLE:"glycogen synthase kinase 3 beta" OR ABSTRACT:"glycogen synthase kinase 3 beta" OR TITLE:"Glycogen synthase kinase-3 beta" OR ABSTRACT:"Glycogen synthase kinase-3 beta") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about GSK3B, not a curated reading list.