GCKR: Glucokinase Regulator
Key regulator of hepatic glucose metabolism and lipid homeostasis
Gene Information Card
| Symbol | GCKR |
|---|---|
| Full Name | Glucokinase Regulator |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 2646 ncbi.nlm.nih.gov/gene/2646 |
| Ensembl ID | ENSG00000184727 |
| UniProt ID | Q14397 |
| OMIM ID | 600842 |
| HGNC ID | 4196 |
| Aliases | GKRP, glucokinase regulatory protein |
Description
The GCKR gene encodes the glucokinase regulatory protein (GKRP), a 68-kDa protein predominantly expressed in the liver. GKRP binds to and inhibits glucokinase (GCK) in the nucleus, sequestering it from the cytoplasm. Upon glucose influx, GKRP dissociates, releasing active GCK to phosphorylate glucose, thereby regulating hepatic glucose uptake and glycogen synthesis. GCKR variants influence fasting glucose, triglycerides, and risk for metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-Onset Diabetes of the Young (MODY) | GCKR mutations alter GKRP-GCK interaction, impairing glucose sensing and insulin secretion; rare variants cause MODY-like phenotypes. | ClinVar, OMIM |
| Hypertriglyceridemia, familial | Common GCKR variants (e.g., rs1260326) reduce GKRP inhibition, increasing GCK activity and hepatic lipogenesis, elevating triglycerides. | ClinVar, NCBI |
| Type 2 Diabetes | GCKR polymorphisms modulate fasting glucose and insulin sensitivity; genome-wide association studies link rs780094 to T2D risk. | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Pancreas | 0.8 | Low |
| Kidney | 0.3 | Not detected |
| Small intestine | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line; high expression |
| Huh7 | 13.8 | Hepatoma cell line; high expression |
| HEK293 | 0.5 | Embryonic kidney; very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1260326 (c.1337C>T, p.Pro446Leu) | SNP | ~40% (global) | Reduces GKRP inhibition of GCK; associated with lower fasting glucose and higher triglycerides. |
| rs780094 (intronic) | SNP | ~35% (global) | Linked to altered GCKR expression; associated with T2D and hypertriglyceridemia. |
| c.94G>A (p.Gly32Arg) | Missense | <0.1% | Rare; disrupts GKRP-GCK binding; reported in MODY families. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) reduce GKRP expression or binding, leading to unregulated GCK activity, hypoglycemia, and increased lipogenesis.
Gain of Function (GOF)
Gain-of-function mutations enhance GKRP inhibition of GCK, causing hyperglycemia and reduced triglyceride synthesis; rare.
Dominant Negative (DN)
Dominant-negative variants (e.g., p.Gly32Arg) produce defective GKRP that sequesters GCK but fails to release it, impairing glucose sensing.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glucokinase regulation in liver
• Glycolysis and gluconeogenesis
• Insulin signaling
• Lipid metabolism
Protein Summary
Glucokinase regulatory protein (GKRP) is a 626-amino acid protein that forms a complex with glucokinase (GCK) in the hepatocyte nucleus. It inhibits GCK by binding to its active site, and this inhibition is relieved by fructose-1-phosphate. GKRP acts as a glucose sensor, modulating hepatic glucose flux. Its structure includes a sugar-binding domain and a GCK-binding region. Post-translational modifications include phosphorylation, which affects stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCKR Knockout HEK293 Cell Line | EDJ-KQ4693 | Human | 2646 | Details Get a Quote |
| GCKR Knockout HeLa Cell Line | EDJ-KQ53318 | Human | 2646 | Details Get a Quote |
| GCKR Knockout A-549 Cell Line | EDJ-KQ61801 | Human | 2646 | Details Get a Quote |
| GCKR Knockout HCT 116 Cell Line | EDJ-KQ70286 | Human | 2646 | Details Get a Quote |
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