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GCKR rs780094-C is associated with increased risk of gestational diabetes mellitus.[meta-analysis]
Mutations in the genes glucokinase regulatory protein (GCKR), RNase L (RNASEL), leukocyte immunoglobulin-like receptor 3 (LILRA3), and dynein axonemal heavy chain 10 (DNAH10) segregated with elevated HDLc levels in families, while no mutations associated with low HDLc.
Three loci showed robust, replicating association with circulating FXI (show F11 Proteins) levels: KNG1 (show KNG1 Proteins) (rs710446, P-value = 2.07 x 10-302), F11 (show F11 Proteins) (rs4253417, P-value = 2.86 x 10-193), and a novel association in GCKR (rs780094, P-value = 3.56 x10-09), here for the first time implicated in FXI (show F11 Proteins) regulation. The two first SNPs (rs710446 and rs4253417) also associated with partial thromboplastin (show F3 Proteins) time
GCKR association with adiposity and the risk of the nonalcoholic fatty liver disease
The existence of a liver-specific FOXA2 (show FOXA2 Proteins)-regulated transcriptional enhancer at an intronic T2D locus represented by rs780094, rs780095, and rs780096 SNPs that increases GCKR expression is demonstrated.
GCKR Leu446 may influence FGF21 (show FGF21 Proteins) expression via its ability to increase glucokinase (GCK (show GCK Proteins)) activity. This can lead to enhanced FGF21 (show FGF21 Proteins) expression via elevated fatty acid synthesis, consequent to the inhibition of carnitine/palmitoyl-transferase by malonyl-CoA, and via increased glucose-6-phosphate-mediated activation of the carbohydrate response element binding protein (show MLXIPL Proteins), known to regulate FGF21 (show FGF21 Proteins) gene expression.
Data suggest that hepatic glucokinase (show GCK Proteins) activity is regulated by reversible binding to specific inhibitor protein glucokinase regulatory protein (GKRP) and by binding to activator proteins such as 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK2 (show PFKFB3 Proteins)/FBP2 (show KHSRP Proteins)); changes in glucokinase (show GCK Proteins) expression and activity are associated with poorly controlled type 2 diabetes and nonalcoholic fatty liver disease. [REVIEW]
The rs780094 [1.34 (1.21-1.49); p = 8.57 x 10(-8) ] on chr 2 at the glucokinase regulatory protein (GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 x 10(-6) ] on chr1 at the laminin subunit gamma-1 (LAMC1 (show LAMC1 Proteins)) locus showed suggestive association with disease.
Among Mexicans, the PNPLA3 (show PNPLA3 Proteins) (rs738409), LYPLAL1 (show LYPLAL1 Proteins) (rs12137855), PPP1R3B (show PPP1R3B Proteins) (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults.
The present study explored the association between a common variant of the glucokinase regulator (GCKR) gene and metabolic syndrome and its related traits in Taiwanese adolescents
This study showed that Sirt2 (show SIRT2 Proteins)-dependent GKRP deacetylation improves impaired HGU and suggest that it may be a therapeutic target for type 2 diabetes.
Given that acetylated GKRP may affiliate with type-2 diabetes mellitus (T2DM), understanding the mechanism of GKRP acetylation in the liver could reveal novel targets within the GK-GKRP pathway, for treating T2DM and other metabolic pathologies.
Glucokinase regulatory protein binds to a super-open conformation of GK mainly through hydrophobic interaction, inhibiting the GK activity by locking a small domain of GK.
This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY).
glucokinase regulatory protein
, glucokinase regulator
, LOW QUALITY PROTEIN: glucokinase regulatory protein
, glucokinase (hexokinase 4) regulator