GSK3B (Glycogen Synthase Kinase 3 Beta)
A multifunctional serine/threonine kinase involved in glycogen metabolism, Wnt signaling, and multiple disease pathways.
Gene Information Card
| Symbol | GSK3B |
|---|---|
| Full Name | Glycogen Synthase Kinase 3 Beta |
| Gene Type | protein-coding |
| Chromosomal Location | 3q13.33 |
| NCBI Gene ID | 2932 ncbi.nlm.nih.gov/gene/2932 |
| Ensembl ID | ENSG00000082701 |
| UniProt ID | P49841 |
| OMIM ID | 605004 |
| HGNC ID | 4617 |
| Aliases | GSK3B, GSK-3beta, GSK3beta, GSK3BETA |
Description
GSK3B (Glycogen Synthase Kinase 3 Beta) is a serine/threonine protein kinase that plays a central role in glycogen metabolism, cell cycle regulation, apoptosis, and signal transduction pathways, including Wnt, PI3K/Akt, and Hedgehog. It is constitutively active in resting cells and is inactivated by phosphorylation at Ser9. Dysregulation of GSK3B is implicated in Alzheimer disease, bipolar disorder, diabetes, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | GSK3B hyperphosphorylates tau protein, leading to neurofibrillary tangles | PMID: 12504013; ClinVar |
| Bipolar disorder | GSK3B is a target of lithium; altered activity affects circadian rhythm and mood regulation | PMID: 17334997; OMIM |
| Diabetes mellitus type 2 | GSK3B inhibits glycogen synthase, contributing to insulin resistance | PMID: 10995757; NCBI Gene |
| Colorectal cancer | GSK3B phosphorylates beta-catenin, promoting its degradation; loss of function leads to Wnt pathway activation | PMID: 10655591; COSMIC |
| Prostate cancer | GSK3B overexpression correlates with poor prognosis and androgen receptor signaling | PMID: 16951133; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.5 | High |
| Heart | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Kidney | 18.1 | Medium |
| Testis | 22.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 32.1 | High expression |
| HeLa | 25.4 | Moderate expression |
| HepG2 | 20.7 | Moderate expression |
| SH-SY5Y | 35.6 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.110C>T (p.Pro37Leu) | Missense | <0.01% | Reduced kinase activity; associated with bipolar disorder |
| c.863G>A (p.Arg288Gln) | Missense | <0.01% | Altered substrate specificity; reported in colorectal cancer |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; rare |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish kinase activity, such as p.Pro37Leu, impair Wnt signaling and may contribute to neurodevelopmental disorders.
Gain of Function (GOF)
Mutations that increase kinase activity, often through loss of inhibitory Ser9 phosphorylation, are linked to tau hyperphosphorylation in Alzheimer disease.
Dominant Negative (DN)
No well-characterized dominant-negative mutations are currently reported in GSK3B.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0005524 (ATP binding) |
| • GO:0006468 (protein phosphorylation) | • GO:0016055 (Wnt signaling pathway) |
| • GO:0046777 (protein autophosphorylation) | • GO:0005813 (centrosome) |
| • GO:0005737 (cytoplasm) |
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Insulin signaling pathway (KEGG: hsa04910)
• Alzheimer disease (KEGG: hsa05010)
• Circadian rhythm (KEGG: hsa04710)
Protein Summary
GSK3B is a 420-amino-acid serine/threonine kinase with a conserved catalytic domain. It is ubiquitously expressed and phosphorylates over 100 substrates, including tau, beta-catenin, and glycogen synthase. Its activity is tightly regulated by phosphorylation, subcellular localization, and protein-protein interactions. GSK3B is a key drug target for Alzheimer disease, bipolar disorder, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSK3B Knockout HEK293 Cell Line | EDJ-KQ902 | Human | 2932 | Details Get a Quote |
| GSK3B Knockout HeLa Cell Line | EDJ-KQ18408 | Human | 2932 | Details Get a Quote |
| GSK3B Knockout A-549 Cell Line | EDJ-KQ19751 | Human | 2932 | Details Get a Quote |
| GSK3B Knockout HCT 116 Cell Line | EDJ-KQ19752 | Human | 2932 | Details Get a Quote |
| GSK3B Knockout HAP1 Cell Line | EDC08001 | Human | 2932 | Details Get a Quote |
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