GCK (Glucokinase) Gene
Key regulator of glucose homeostasis and MODY2 diabetes
Gene Information Card
| Symbol | GCK |
|---|---|
| Full Name | Glucokinase |
| Gene Type | Protein coding |
| Chromosomal Location | 7p13 |
| NCBI Gene ID | 2645 ncbi.nlm.nih.gov/gene/2645 |
| Ensembl ID | ENSG00000106633 |
| UniProt ID | P35557 |
| OMIM ID | 138079 |
| HGNC ID | 4195 |
| Aliases | GK, GLK, HHF3, HK4, HXKP, MODY2, hexokinase 4 |
Description
The GCK gene encodes glucokinase, a hexokinase isozyme that catalyzes the first step of glycolysis, converting glucose to glucose-6-phosphate. It acts as a glucose sensor in pancreatic beta cells and regulates glucose metabolism in the liver. Mutations in GCK cause maturity-onset diabetes of the young type 2 (MODY2) and can also lead to hyperinsulinemic hypoglycemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maturity-onset diabetes of the young type 2 (MODY2) | Heterozygous inactivating mutations reduce glucokinase activity, impairing glucose sensing and insulin secretion, leading to mild fasting hyperglycemia. | ClinVar, OMIM |
| Permanent neonatal diabetes mellitus (PNDM) | Homozygous or compound heterozygous inactivating mutations cause complete loss of glucokinase function, resulting in severe insulin deficiency. | ClinVar, OMIM |
| Hyperinsulinemic hypoglycemia (HHF3) | Activating mutations increase glucokinase activity, causing excessive insulin secretion and hypoglycemia. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.3 | Medium |
| Liver | 8.7 | Medium |
| Brain | 1.2 | Low |
| Small intestine | 0.8 | Low |
| Kidney | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (beta cell) | 15.2 | Rat insulinoma line |
| HepG2 | 9.1 | Human hepatoma line |
| HeLa | 0.3 | Cervical cancer line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.683C>T (p.Thr228Met) | Missense | Common in MODY2 | Reduced enzyme activity |
| c.784G>A (p.Glu262Lys) | Missense | Rare | Loss of function |
| c.1139G>A (p.Arg380His) | Missense | Rare | Gain of function, hypoglycemia |
| c.145C>T (p.Arg49Trp) | Missense | Rare | Dominant negative effect |
Mutation functional classification
Loss of Function (LOF)
Heterozygous loss-of-function mutations cause MODY2; homozygous cause PNDM.
Gain of Function (GOF)
Activating mutations cause hyperinsulinemic hypoglycemia (HHF3).
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg49Trp) exert a dominant negative effect, reducing overall glucokinase activity.
View complete mutation data：
Gene Ontology (GO)
| • glucokinase activity (GO:0004340) | • glucose binding (GO:0005536) |
| • glycolytic process (GO:0006096) | • glucose homeostasis (GO:0042593) |
| • insulin secretion (GO:0030073) |
Pathways
• Glycolysis (Reactome:R-HSA-70171)
• Glucose metabolism (KEGG:hsa00010)
• Maturity onset diabetes of the young (KEGG:hsa04950)
Protein Summary
Glucokinase (UniProt P35557) is a 465-amino acid protein that functions as a monomeric enzyme with a molecular weight of approximately 52 kDa. It has a low affinity for glucose (Km ~8 mM) and is not inhibited by glucose-6-phosphate, allowing it to act as a glucose sensor. The protein is expressed primarily in pancreatic beta cells and hepatocytes, where it regulates insulin secretion and hepatic glucose uptake.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCK Knockout HEK293 Cell Line | EDJ-KQ3139 | Human | 2645 | Details Get a Quote |
| GCKR Knockout HEK293 Cell Line | EDJ-KQ4693 | Human | 2646 | Details Get a Quote |
| PGCKA1 Knockout HEK293 Cell Line | EDJ-KQ51443 | Human | 55286 | Details Get a Quote |
| GCK Knockout HeLa Cell Line | EDJ-KQ53317 | Human | 2645 | Details Get a Quote |
| GCKR Knockout HeLa Cell Line | EDJ-KQ53318 | Human | 2646 | Details Get a Quote |
| PGCKA1 Knockout HeLa Cell Line | EDJ-KQ56571 | Human | 55286 | Details Get a Quote |
| GCK Knockout A-549 Cell Line | EDJ-KQ61800 | Human | 2645 | Details Get a Quote |
| GCKR Knockout A-549 Cell Line | EDJ-KQ61801 | Human | 2646 | Details Get a Quote |
| PGCKA1 Knockout A-549 Cell Line | EDJ-KQ65068 | Human | 55286 | Details Get a Quote |
| GCK Knockout HCT 116 Cell Line | EDJ-KQ70285 | Human | 2645 | Details Get a Quote |
| GCKR Knockout HCT 116 Cell Line | EDJ-KQ70286 | Human | 2646 | Details Get a Quote |
| PGCKA1 Knockout HCT 116 Cell Line | EDJ-KQ73513 | Human | 55286 | Details Get a Quote |
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