Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

Official Name


Name from literature


Pathway from literature


Pathway from KEGG

Cellular Processes; Endocrine System; Insulin signaling pathway; map04910

Cellular Processes; Endocrine System; Adipocytokine signaling pathway; map04920

Carbohydrate Metabolism; Starch and sucrose metabolism; map00500

Carbohydrate Metabolism; Glycolysis / Gluconeogenesis; map00010

Carbohydrate Metabolism; Galactose metabolism; map00052


Human (9606)

Genome localization

17q21[2538 ], 2q24.3[57818 ],


Wide distribution in animal tissues. Also catalyses potent transphosphorylations from carbamoyl phosphate, hexose phosphates, diphosphate, phosphoenolpyruvate and nucleoside di- and triphosphates, to D-glucose, D-mannose, 3-methyl-D-glucose or 2-deoxy-D-glucose [cf. EC (phosphoramidate---hexose phosphotransferase), EC (diphosphate---glycerol phosphotransferase) and EC (phosphoamidase)].

Rate-limiting Description

"Glucose-6-phosphatase (G6Pase) catalyzes the rate-limiting step of gluconeogenesis, and hepatic G6Pase activity is increased in diabetes." (9506766)

Regulatory Information

Upstream transcription factor


Regulatory type



"During catalysis, a His residue in G6Pase becomes phosphorylated generating an enzyme-phosphate intermediate." (12093795)

transcriptional factor;"HNF4alpha(3172),CREM(1390),HNF1alpha(6927),C/EBPalpha(1050)"

"Here we specify the cAMP/protein kinase A regulation of the Glc6Pase gene in the intestine compared with the liver. Similarly to the liver, the molecular mechanism of cAMP/protein kinase A regulation involves cAMP-response element-binding protein, HNF4alpha, CAAT/enhancer-binding protein, and HNF1." (16893891)

key enzyme;

"Glucose-6-phosphatase-alpha (G6PC) is a key enzyme in glucose homeostasis that catalyzes the hydrolysis of glucose-6-phosphate to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis." (18449899)


"maximum repression of basal glucose-6-phosphatase catalytic subunit (G6Pase) gene transcription by insulin requires two distinct promoter regions, designated that together form an insulin response unit." (12556524)

transcriptional factor;"HNF4alpha(3172),CREM(1390),HNF1alpha(6927),C/EBPalpha(1050)"

"HNF4alpha, CREM, HNF1alpha, and C/EBPalpha have roles in transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine" (16893891)

transcriptional factor;FOXO1(2308)

"Antagonistic effects of phorbol esters on insulin regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) but not glucose-6-phosphatase gene expression." (11672436)

Gene ontology

Gene ontology

GO:0004346 (F) glucose-6-phosphatase activity [P35575, Q9NQR9, Q9BUM1 ];
GO:0016021 (C) integral to membrane [Q9NQR9, Q9BUM1 ];
GO:0042301 (F) phosphate binding [P35575 ];
GO:0006094 (P) gluconeogenesis [P35575, Q9NQR9, Q9BUM1 ];
GO:0042593 (P) glucose homeostasis [P35575 ];
GO:0005789 (C) endoplasmic reticulum membrane [Q9NQR9, Q9BUM1 ];
GO:0030176 (C) integral to endoplasmic reticulum membrane [P35575 ];

Tissue expression

Tissue From HPRD

Gall bladder [01983 ];
Kidney [01983 ];
Testis [16272, 01983 ];
Islets of Langerhans [16272 ];
Pancreas [16272 ];
Liver [01983 ];
Placenta [01983 ];
Brain [01983 ];

Tissue specificity

Ubiquitously expressed. Highly expressed in skeletal muscle, at intermediate levels in heart, brain, placenta, kidney, colon, thymus, spleen and pancreas. Also detected in testis, prostate, ovary, liver, lung, small intestine and peripheral blood lymphocytes [Q9BUM1 ];

Specifically expressed in pancreas and also detected to a lower extent in testis. Expressed by most islet cells in the pancreas (at protein level) [Q9NQR9 ];

Subcellular localization


endoplasmic reticulum [P35575, Q9NQR9, Q9BUM1 ];

Disease relevance


Defects in G6PC are the cause of glycogen storage disease type 1A (GSD1A) [MIM:232200];
also known as von Gierke disease. GSD1A is a metabolic disorder characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. GSD1 patients manifest a wide range of clinical symptoms and biochemical abnormalities, including hypoglycemia, severe hepatomegaly due to excessive accumulation of glycogen, kidney enlargement, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia [P35575 ];

Genetic variation in G6PC2 is associated with fasting plasma glucose levels quantitative trait locus type 1 (FGQTL1) [MIM:612108]. The normal fasting plasma glucose level in the plasma is defined as less than 100 mg per deciliter (5.55 mmol per liter). Higher fasting plasma glucose levels predict type 2 diabetes in young adults and increases the risk of mortality [Q9NQR9 ];



P35575; Q9BUM1; Q9NQR9

Entrez Gene

2538; 57818


01983; 16272

  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min