GCK across dismech

GCK (glucokinase) is named by 4 disorder entries.

Normal function

ai-gene-review gives GCK's core molecular function as glucokinase activity, acting in glucose homeostasis; glucose metabolic process; and glycolytic process. Glucokinase's low glucose affinity makes it the glucose sensor of the pancreatic beta cell and the hepatocyte. The upstream review is being updated to add the beta-cell insulin-secretion role to its core functions.

Causative records

Three entries type GCK as causative: Congenital Isolated Hyperinsulinism; Diabetes mellitus; and Hyperinsulinemic Hypoglycemia. All three record the variants as germline (Congenital Isolated Hyperinsulinism; Diabetes mellitus; and Hyperinsulinemic Hypoglycemia).

The hyperinsulinism entries carry the activating (gain-of-function) arm. In Congenital Isolated Hyperinsulinism the gene sits on the node Glucokinase Glucose-Sensing Threshold Shift, and in Hyperinsulinemic Hypoglycemia on Lowered Beta-Cell Glucose Set-Point. The inactivating arm (GCK-MODY and permanent neonatal diabetes) appears in Diabetes mellitus, on the node Monogenic Beta-Cell Dysfunction.

ClinGen rates GCK definitive for the hyperinsulinism of Congenital Isolated Hyperinsulinism and definitive for the monogenic diabetes matched to Diabetes mellitus.

Where the layers disagree

Type 2 Diabetes Mellitus names GCK but has no genetic record for it.

The KB's GCK nodes are annotated with insulin-secretion processes (insulin secretion; and regulation of insulin secretion), while the ingested ai-gene-review core functions describe glucose metabolism and homeostasis, so the two share 0 GO process terms by exact identifier. The molecular function does agree: Congenital Isolated Hyperinsulinism binds glucokinase activity, marked increased, on its GCK node.