Target intelligence / Profile preview

Glucose-6-phosphatase catalytic subunit (G6PC)

Target
G6PC
Molecular classification
Enzyme, Integral membrane protein
01

Overview

Glucose-6-phosphatase catalytic subunit (G6PC) is a critical enzyme located on the endoplasmic reticulum membrane that catalyzes the final step of gluconeogenesis and glycogenolysis—the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. It is a key regulator of blood glucose homeostasis, allowing the release of glucose from the liver and kidney into the bloodstream, especially during fasting conditions. Deficiency of G6PC leads to glycogen storage disease type I (von Gierke disease), characterized by severe hypoglycemia, hepatomegaly, nephromegaly, and metabolic disturbances. The protein is part of a multicomponent system, acting in concert with the glucose-6-phosphate transporter (SLC37A4), and its function is essential for proper metabolic adaptation to fasting and feeding states.

Other names
Glucose 6-phosphataseG6PaseG6PC1G6Pase-alphaGlucose-6-phosphatase alphaG6PC_HUMAN
02

Mechanism of action

Enzyme catalyzes the hydrolysis of glucose-6-phosphate to free glucose and inorganic phosphate, which is essential for maintaining blood glucose levels, especially during fasting states.

03

Biological functions

GluconeogenesisGlycogenolysisGlucose homeostasis
04

Disease associations

Genetic metabolic disease (notably Glycogen storage disease type I / von Gierke disease)Diabetes (associative/dysregulation)Other
05

Safety considerations

Hypoglycemia as a result of loss-of-functionRisk of glycogen and lipid accumulation in liver and kidney in deficiency states, leading to organ dysfunctionNo direct drug target safety profile established, but gene therapy or pharmacological enzyme modulation would require careful monitoring to avoid hypoglycemia or disturbance of glucose homeostasis
06

Biomarkers

Mutational analysis for G6PC1 serves as a diagnostic genetic biomarker for glycogen storage disease type ILiver or serum glucose-6-phosphatase activity is sometimes a research proxy for functional studies

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