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  3. GCK

GCK (Glucokinase)

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Summary of GCK

The gene codes for a protein, glucokinase. Mutations are linked to non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) [R].

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The Function of GCK

Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage.

Protein names

Recommended name:

Glucokinase

Short name:

HK4

Alternative name(s):

Hexokinase type IV
HK IV
Hexokinase-4
Hexokinase-D

GCK SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS1799884 (GCK) ??
  2. RS3757840 (GCK) ??
  3. RS4607517 (GCK) ??
  4. RS730497 (GCK) ??

Top Gene-Substance Interactions

GCK Interacts with These Diseases

Disease Score

Substances That Increase GCK

Substances Interaction Organism Category

Substances That Decrease GCK

Substances Interaction Organism Category

Advanced Summary

     Covered on Genetics Home Reference: congenital hyperinsulinismpermanent neonatal diabetes mellitusFrom NCBI Gene: Diabetes mellitus type 2Maturity-onset diabetes of the young, type 2Permanent neonatal diabetes mellitusHyperinsulinemic hypoglycemia familial 3From UniProt: Familial hyperinsulinemic hypoglycemia 3 (HHF3): Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. [MIM:602485] Maturity-onset diabetes of the young 2 (MODY2): A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. [MIM:125851]

     From NCBI Gene: Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. Alternative splicing of this gene results in three tissue-specific forms of glucokinase, one found in pancreatic islet beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). [provided by RefSeq, Apr 2009] From UniProt: Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • ER-alpha
  • AP-1
  • c-Jun
  • Pax-6
  • HNF-4alpha1
  • HNF-4alpha2
  • STAT5A
  • SREBP-1a
  • SREBP-1c
  • SREBP-1b

Tissue specificity:

Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver.

Gene Pathways:

  • Metabolic pathways
  • Metabolism
  • Disease
  • Insulin signaling pathway
  • Amino sugar and nucleotide sugar metabolism
  • Glycolysis / Gluconeogenesis
  • Transmembrane transport of small molecules
  • Type II diabetes mellitus
  • Galactose metabolism
  • Maturity onset diabetes of the young
  • Starch and sucrose metabolism
  • Regulation of Beta-Cell Development
  • Butirosin and neomycin biosynthesis

Enzyme Regulation:

The use of alternative promoters apparently enables the type IV hexokinase gene to be regulated by insulin in the liver and glucose in the beta cell. This may constitute an important feedback loop for maintaining glucose homeostasis. Subject to allosteric regulation. Low glucose and high fructose-6-phosphate triggers association with the inhibitor GKRP followed by sequestration in the nucleus.

Molecular Function:

  • Atp Binding
  • Glucokinase Activity
  • Glucose Binding
  • Adp Binding
  • Magnesium Ion Binding

Biological Processes:

  • Calcium Ion Import
  • Canonical Glycolysis
  • Cellular Glucose Homeostasis
  • Cellular Response To Insulin Stimulus
  • Cellular Response To Leptin Stimulus
  • Detection Of Glucose
  • Glucose Homeostasis
  • Glucose Transport
  • Glycolytic Process
  • Nadp Metabolic Process
  • Negative Regulation Of Gluconeogenesis
  • Positive Regulation Of Glycogen Biosynthetic Process
  • Positive Regulation Of Insulin Secretion
  • Regulation Of Glucose Transport
  • Regulation Of Glycolytic Process
  • Regulation Of Insulin Secretion
  • Regulation Of Potassium Ion Transport
  • Cellular Response To Glucose Starvation
  • Fructose 2,6-Bisphosphate Metabolic Process
  • Glycogen Biosynthetic Process
  • Lipid Homeostasis
  • Negative Regulation Of Epinephrine Secretion
  • Positive Regulation Of Cytosolic Calcium Ion Concentration
  • Positive Regulation Of Glycolytic Process
  • Second-Messenger-Mediated Signaling
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| Gk| AS27_10957| ATP:D-hexose 6-phosphotransferase| D623_10014903| EGK_13734| EH28_15653| fb57f10| FGQTL3| GLK| Gls006| glucokinase (hexokinase 4)| glucokinase (hexokinase 4, maturity onset diabetes of the young 2)| glucokinase variant 3| GLUKA| GW7_08265| hex4| Hexokinase-2| hexokinase 4| hexokinase-4| hexokinase-D| hexokinase D, pancreatic isozyme| hexokinase type IV| HHF3| hk4| hkiv| HK IV| Hlb62| hxkp| I79_011857| LGLK| M91_15821| M959_06862| MODY2| N305_02362| N307_06248| N309_09285| N310_02111| N322_07182| N334_05349| PANDA_013319| RNGK2| TREES_T100018882| Y1Q_016837| Y956_10380| gck

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