# GSK3B

Source: https://onco.cc/targets/gsk3b/  
OnCo record `gsk3b` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: glycogen synthase kinase 3 beta; Glycogen synthase kinase-3 beta
- Tags: cancer-genes-wave
- Symbol: GSK3B
- Class: kinase
- 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).
- Where found: Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (STAD)

## 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.

## Sources

- HGNC HGNC:4617: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4617
- UniProt P49841: https://www.uniprot.org/uniprotkb/P49841/entry
- NCBI Gene 2932: https://www.ncbi.nlm.nih.gov/gene/2932
- Ensembl ENSG00000082701: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000082701

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/)

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JSON: https://onco.cc/api/v1/entities/gsk3b.json