GANAB

Glucose-6-phosphatase 3 (G6PC3) is an enzyme that in humans is encoded by the G6PC3 gene. This enzyme is a member of the glucose-6-phosphatase family, which plays a critical role in gluconeogenesis and glycogenolysis.

Function

G6PC3 is primarily involved in the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. This reaction is a key step in the regulation of blood glucose levels, particularly during fasting states. Unlike other glucose-6-phosphatase isoforms, G6PC3 is ubiquitously expressed in various tissues, including the liver, kidney, and pancreas.

Clinical Significance

Mutations in the G6PC3 gene are associated with a rare genetic disorder known as severe congenital neutropenia type 4 (SCN4). This condition is characterized by a deficiency of neutrophils, a type of white blood cell essential for fighting infections. Patients with SCN4 often present with recurrent infections, failure to thrive, and other hematological abnormalities.

Pathophysiology

The pathophysiology of SCN4 involves impaired glucose metabolism due to dysfunctional G6PC3, leading to increased apoptosis of neutrophil precursors in the bone marrow. This results in neutropenia and the associated clinical manifestations.

Genetic Information

The G6PC3 gene is located on chromosome 17q21.31. It consists of several exons and encodes a protein that is approximately 346 amino acids in length. Various mutations, including missense, nonsense, and splice-site mutations, have been identified in patients with SCN4.

Diagnosis and Management

Diagnosis of SCN4 involves genetic testing to identify mutations in the G6PC3 gene. Management of the condition typically includes administration of granulocyte colony-stimulating factor (G-CSF) to stimulate neutrophil production and reduce the risk of infections. Regular monitoring and supportive care are also essential components of patient management.

Research Directions

Ongoing research is focused on understanding the broader implications of G6PC3 deficiency and exploring potential gene therapy approaches. Studies are also investigating the role of G6PC3 in other metabolic pathways and its potential involvement in additional clinical phenotypes.

Also see

• Gluconeogenesis
• Glycogenolysis
• Neutropenia
• Granulocyte colony-stimulating factor
• Congenital neutropenia