GYS2 Gene: Glycogen Synthase 2 – Function, Disease Associations, and Clinical Significance
Comprehensive biomedical overview of GYS2, including gene structure, expression, mutations, and associated disorders.
Gene Information Card
| Symbol | GYS2 |
|---|---|
| Full Name | Glycogen synthase 2 (liver) |
| Gene Type | protein coding |
| Chromosomal Location | 12p12.1 |
| NCBI Gene ID | 2998 ncbi.nlm.nih.gov/gene/2998 |
| Ensembl ID | ENSG00000111713 |
| UniProt ID | P54840 |
| OMIM ID | 138571 |
| HGNC ID | 4707 |
| Aliases | GSY2, glycogen synthase, liver |
Description
The GYS2 gene encodes glycogen synthase 2, the liver isoform of glycogen synthase, which catalyzes the rate-limiting step in glycogen synthesis by transferring glucose from UDP-glucose to the growing glycogen chain. This enzyme is primarily expressed in the liver and is regulated by both allosteric activation (glucose-6-phosphate) and covalent modification (phosphorylation/dephosphorylation). Mutations in GYS2 cause glycogen storage disease type 0 (GSD0), characterized by fasting hypoglycemia and postprandial hyperglycemia. GYS2 is also implicated in other metabolic conditions and is a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen storage disease type 0 (GSD0) | Loss-of-function mutations in GYS2 reduce hepatic glycogen synthesis, leading to fasting hypoglycemia and postprandial hyperglycemia. | ClinVar, OMIM |
| Hyperglycemia / Type 2 diabetes (susceptibility) | Variants in GYS2 may impair glycogen synthesis, contributing to insulin resistance and hyperglycemia. | PubMed, ClinVar |
| Non-alcoholic fatty liver disease (NAFLD) | Altered GYS2 expression may affect hepatic glycogen storage and lipid metabolism, though direct causal evidence is limited. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (nTPM ~ 100) | High |
| Kidney | Low (nTPM ~ 5) | Low |
| Small intestine | Low (nTPM ~ 3) | Low |
| Adipose tissue | Not detected | Not detected |
| Skeletal muscle | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver carcinoma) | High | Liver-derived cell line; high GYS2 expression |
| HEK293 (embryonic kidney) | Low | Low expression; used for recombinant studies |
| HeLa (cervical carcinoma) | Not detected | No significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1006C>T (p.Arg336Ter) | Nonsense | Rare | Truncated protein; loss of function |
| c.1210G>A (p.Gly404Ser) | Missense | Rare | Impaired catalytic activity |
| c.1346A>G (p.Tyr449Cys) | Missense | Rare | Reduced enzyme activity |
| c.1600C>T (p.Arg534Trp) | Missense | Rare | Loss of function; associated with GSD0 |
Mutation functional classification
Loss of Function (LOF)
Most GYS2 mutations are loss-of-function, leading to reduced or absent glycogen synthase activity, causing GSD0.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GYS2.
Dominant Negative (DN)
No dominant-negative effects have been documented; GYS2 mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • glycogen synthase activity (GO:0004373) | • glycogen biosynthetic process (GO:0005978) |
| • UDP-glucose binding (GO:0030345) | • glucose-6-phosphate binding (GO:0030346) |
| • cytoplasm (GO:0005737) | • glycogen particle (GO:0042587) |
Pathways
• Glycogen metabolism (Reactome: R-HSA-8982491)
• Insulin signaling pathway (KEGG: hsa04910)
• Starch and sucrose metabolism (KEGG: hsa00500)
Protein Summary
Glycogen synthase 2 (GYS2) is a 703-amino acid protein (UniProt P54840) that exists as a homotetramer and catalyzes the addition of glucose residues to glycogen. It is regulated by phosphorylation at multiple serine residues (inactivating) and allosteric activation by glucose-6-phosphate. The protein is predominantly expressed in the liver, where it plays a central role in maintaining blood glucose homeostasis. Defects in GYS2 lead to glycogen storage disease type 0, a metabolic disorder with clinical features of fasting hypoglycemia and postprandial hyperglycemia. The enzyme is a target for therapeutic intervention in metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GYS2 Knockout HEK293 Cell Line | EDJ-KQ805 | Human | 2998 | Details Get a Quote |
| GYS2 Knockout HeLa Cell Line | EDJ-KQ53468 | Human | 2998 | Details Get a Quote |
| GYS2 Knockout A-549 Cell Line | EDJ-KQ61940 | Human | 2998 | Details Get a Quote |
| GYS2 Knockout HCT 116 Cell Line | EDJ-KQ70421 | Human | 2998 | Details Get a Quote |
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