GCK

About GCK

GCK on chromosome 7p13 encodes glucokinase, an enzyme that phosphorylates glucose and acts as the glucose sensor of pancreatic beta cells and liver cells, setting the blood glucose level at which insulin is released. Heterozygous inactivating variants raise this set point slightly, causing GCK maturity onset diabetes of the young, often called MODY2, characterized by mild, stable fasting hyperglycemia present from birth that typically does not worsen with age. Complications of diabetes are rare in this form, and it is often discovered incidentally, for example during pregnancy. Inactivating variants on both copies of the gene cause permanent neonatal diabetes, a much more severe condition. Activating variants have the opposite effect, lowering the set point and causing hyperinsulinemic hypoglycemia. GCK is a classic example of how the degree of change in a single protein shifts a physiological threshold.