Gene: GCK

Alternate names for this Gene: FGQTL3|GK|GLK|HHF3|HK4|HKIV|HXKP|LGLK|MODY2|PNDM1

Gene Summary: This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. 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. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia.

Gene is located in Chromosome: 7

Location in Chromosome : 7p13

Description of this Gene: glucokinase

Type of Gene: protein-coding

rs2971669 in GCK gene and Birth Weight PMID 29309628 2018 Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.

PMID 31043758 2019 Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

rs2070971 in GCK gene and Body Height PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs2908296 in GCK gene and Body mass index PMID 28892062 2017 Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.

PMID 22581228 2012 A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

rs1286804191 in GCK gene and DIABETES MELLITUS, PERMANENT NEONATAL PMID 11372010 2001 Neonatal diabetes mellitus due to complete glucokinase deficiency.

PMID 25015100 2014 Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.

rs1799884 in GCK gene and Diabetes Mellitus, Non-Insulin-Dependent PMID 23575436 2013 New susceptibility loci in MYL2, C12orf51 and OAS1 associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes in the Korean population.

rs104894010 in GCK gene and Diabetes mellitus autosomal dominant type II (disorder) PMID 8325892 1993 Structure/function studies of human beta-cell glucokinase. Enzymatic properties of a sequence polymorphism, mutations associated with diabetes, and other site-directed mutants.

PMID 11106831 2000 Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus.

PMID 10588527 1999 Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY.

PMID 1303265 1992 Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes.

PMID 1502186 1992 Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus.

PMID 25015100 2014 Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.

PMID 19884385 2009 Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene.

PMID 22611063 2012 Insights into the pathogenicity of rare missense GCK variants from the identification and functional characterization of compound heterozygous and double mutations inherited in cis.

PMID 17573900 2007 Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain.

PMID 8495817 1993 Identification of glucokinase mutations in subjects with gestational diabetes mellitus.

PMID 16965331 2006 Identification of novel and recurrent glucokinase mutations in Belgian and Luxembourg maturity onset diabetes of the young patients.

PMID 8878425 1996 Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects.

PMID 8446612 1993 Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships.

PMID 18322640 2008 Biochemical characterization of novel glucokinase mutations isolated from Spanish maturity-onset diabetes of the young (MODY2) patients.

PMID 9049484 1997 Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families.

PMID 9662401 1998 Mutations in the glucokinase gene of the fetus result in reduced birth weight.

PMID 1464666 1992 Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus.

PMID 8168652 1994 Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique.

PMID 11372010 2001 Neonatal diabetes mellitus due to complete glucokinase deficiency.

PMID 10694920 1998 Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). Mutations in brief no. 162. Online.

PMID 19339519 2009 Human Splicing Finder: an online bioinformatics tool to predict splicing signals.

PMID 19790256 2009 Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

PMID 14517946 2003 Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.

PMID 19187021 2009 Biochemical characterization of MODY2 glucokinase variants V62M and G72R reveals reduced enzymatic activities relative to wild type.

PMID 18399931 2008 Diagnostic screening of MODY2/GCK mutations in the Norwegian MODY Registry.

PMID 27271189 2016 Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes.

PMID 15677479 2005 Insights into the structure and regulation of glucokinase from a novel mutation (V62M), which causes maturity-onset diabetes of the young.

PMID 9736233 1998 A missense mutation, Val62Ala, in the glucokinase gene in a Norwegian family with maturity-onset diabetes of the young.

PMID 17389332 2007 Cell biology assessment of glucokinase mutations V62M and G72R in pancreatic beta-cells: evidence for cellular instability of catalytic activity.

PMID 16731834 2006 From clinicogenetic studies of maturity-onset diabetes of the young to unraveling complex mechanisms of glucokinase regulation.

PMID 25182307 2014 ISPAD Clinical Practice Consensus Guidelines 2014. The diagnosis and management of monogenic diabetes in children and adolescents.

PMID 11508276 2001 High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI.

PMID 11079754 2000 "MODY 2 presenting as neonatal hyperglycaemia: a need to reshape the definition of ""neonatal diabetes""?"

PMID 30155490 2018 Lower Circulating miR-122 Level in Patients with HNF1A Variant-Induced Diabetes Compared with Type 2 Diabetes.

PMID 24430320 2014 Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia.

PMID 30592380 2019 Identification and functional analysis of GCK gene mutations in 12 Chinese families with hyperglycemia.

rs1799884 in GCK gene and Fasting blood glucose measurement PMID 22885924 2012 Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

PMID 21909109 2011 Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 19060907 2009 Variants in MTNR1B influence fasting glucose levels.

PMID 25631608 2015 Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.

PMID 20081858 2010 New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

PMID 22508271 2012 Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA).

PMID 22581228 2012 A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

rs1799884 in GCK gene and Fasting blood sugar result PMID 22885924 2012 Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

rs2971672 in GCK gene and Glucose measurement PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

rs1057524900 in GCK gene and Hyperglycemia PMID 14517956 2003 Identification of 21 novel glucokinase (GCK) mutations in UK and European Caucasians with maturity-onset diabetes of the young (MODY).

PMID 22035297 2012 Doubling the referral rate of monogenic diabetes through a nationwide information campaign--update on glucokinase gene mutations in a Polish cohort.

PMID 20337973 2010 Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations.

PMID 16602010 2006 Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents.

PMID 17204055 2007 Six novel mutations in the GCK gene in MODY patients.

PMID 19150152 2009 Novel mutations in GCK and HNF1A genes in Italian families with MODY phenotype.

PMID 19790256 2009 Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

PMID 14517946 2003 Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.

PMID 19339519 2009 Human Splicing Finder: an online bioinformatics tool to predict splicing signals.

PMID 19187021 2009 The glucokinase V62M and G72R mutations are naturally occurring and known to associate with hyperglycemia in humans.

PMID 17389332 2007 These results suggest that cellular loss of GK catalytic activity rather than impaired translation or enhanced protein degradation may account for the hyperglycemia in subjects with V62M and G72R mutations.

PMID 18399931 2008 Diagnostic screening of MODY2/GCK mutations in the Norwegian MODY Registry.

PMID 27271189 2016 Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes.

PMID 15677479 2005 We studied the GCK V62M mutation identified in two families and co-segregating with hyperglycemia to understand how this mutation resulted in reduced function.

PMID 9736233 1998 A missense mutation, Val62Ala, in the glucokinase gene in a Norwegian family with maturity-onset diabetes of the young.

PMID 16731834 2006 From clinicogenetic studies of maturity-onset diabetes of the young to unraveling complex mechanisms of glucokinase regulation.

PMID 11079754 2000 "MODY 2 presenting as neonatal hyperglycaemia: a need to reshape the definition of ""neonatal diabetes""?"

PMID 25182307 2014 ISPAD Clinical Practice Consensus Guidelines 2014. The diagnosis and management of monogenic diabetes in children and adolescents.

PMID 11508276 2001 High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI.

PMID 17573900 2007 Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain.

PMID 25015100 2014 Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.

PMID 22493702 2012 Identification and functional characterisation of novel glucokinase mutations causing maturity-onset diabetes of the young in Slovakia.

PMID 19358091 2009 Glucokinase gene mutation screening in Argentinean clinically characterized MODY patients.

PMID 11942313 2002 To: Lindner T, Cockburn BN, Bell GI (1999). Molecular genetics of MODY in Germany. Diabetologia 42: 121-123.

PMID 22611063 2012 Insights into the pathogenicity of rare missense GCK variants from the identification and functional characterization of compound heterozygous and double mutations inherited in cis.

rs104894012 in GCK gene and Hyperinsulinemic hypoglycemia, familial, 3 PMID 11916951 2002 The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy.

PMID 12941786 2003 Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations.

PMID 20375417 2010 Large islets, beta-cell proliferation, and a glucokinase mutation.

PMID 15277402 2004 Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation.

PMID 9435328 1998 Familial hyperinsulinism caused by an activating glucokinase mutation.

PMID 17082186 2006 Biochemical basis of glucokinase activation and the regulation by glucokinase regulatory protein in naturally occurring mutations.

PMID 19884385 2009 Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene.

PMID 28247534 2017 Heterogeneity in phenotype of hyperinsulinism caused by activating glucokinase mutations: a novel mutation and its functional characterization.

rs3757840 in GCK gene and Metabolic Syndrome X PMID 22399527 2012 Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits.

rs1057524900 in GCK gene and Monogenic diabetes PMID 22035297 2012 Doubling the referral rate of monogenic diabetes through a nationwide information campaign--update on glucokinase gene mutations in a Polish cohort.

PMID 17204055 2007 Six novel mutations in the GCK gene in MODY patients.

PMID 20337973 2010 Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations.

PMID 14517956 2003 Identification of 21 novel glucokinase (GCK) mutations in UK and European Caucasians with maturity-onset diabetes of the young (MODY).

PMID 16602010 2006 Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents.

PMID 14517946 2003 Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.

PMID 19790256 2009 Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

PMID 19150152 2009 Novel mutations in GCK and HNF1A genes in Italian families with MODY phenotype.

PMID 19339519 2009 Human Splicing Finder: an online bioinformatics tool to predict splicing signals.

PMID 19358091 2009 Glucokinase gene mutation screening in Argentinean clinically characterized MODY patients.

PMID 17573900 2007 Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain.

PMID 22493702 2012 Identification and functional characterisation of novel glucokinase mutations causing maturity-onset diabetes of the young in Slovakia.

PMID 25015100 2014 Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.

PMID 11942313 2002 To: Lindner T, Cockburn BN, Bell GI (1999). Molecular genetics of MODY in Germany. Diabetologia 42: 121-123.

PMID 22611063 2012 Both our functional and genetic studies support R43H as the cause of GCK-MODY and G68D as a neutral rare variant.

rs758737171 in GCK gene and Overgrowth PMID 19790256 2009 Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

PMID 15277402 2004 Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation.

PMID 21454522 2011 Discovery of a novel site regulating glucokinase activity following characterization of a new mutation causing hyperinsulinemic hypoglycemia in humans.

PMID 27130141 2016 Maturity-Onset Diabetes of the Young (MODY): Making the Right Diagnosis to Optimize Treatment.

PMID 24890200 2014 Familial adult onset hyperinsulinism due to an activating glucokinase mutation: implications for pharmacological glucokinase activation.

rs1799884 in GCK gene and Serum albumin measurement PMID 21909109 2011 Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.

PMID 23281178 2013 A genome-wide assessment of variability in human serum metabolism.

rs3757840 in GCK gene and Systolic Pressure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs2070971 in GCK gene and Triglycerides measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

rs2971672 in GCK gene and elevated blood glucose level PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.