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Aliases for GCK Gene

Aliases for GCK Gene

  • Glucokinase 2 3 3 5
  • Glucokinase (Hexokinase 4) 2 3
  • Hexokinase Type IV 3 4
  • HK IV 3 4
  • HK4 3 4
  • Maturity Onset Diabetes Of The Young 2 2
  • ATP:D-Hexose 6-Phosphotransferase 3
  • Hexokinase D, Pancreatic Isozyme 3
  • Hexokinase 4 2
  • Hexokinase-4 4
  • Hexokinase-D 4
  • EC 2.7.1.2 4
  • EC 2.7.1 61
  • FGQTL3 3
  • MODY2 3
  • HHF3 3
  • HKIV 3
  • HXKP 3
  • LGLK 3
  • GLK 3
  • GK 3

External Ids for GCK Gene

Previous HGNC Symbols for GCK Gene

  • MODY2

Previous GeneCards Identifiers for GCK Gene

  • GC07M043830
  • GC07M043890
  • GC07M043924
  • GC07M043957
  • GC07M044150
  • GC07M044183
  • GC07M044070

Summaries for GCK Gene

Entrez Gene Summary for GCK 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]

GeneCards Summary for GCK Gene

GCK (Glucokinase) is a Protein Coding gene. Diseases associated with GCK include Hyperinsulinemic Hypoglycemia, Familial, 3 and Mody, Type Ii. Among its related pathways are Metabolism and Transport of the SLBP independent Mature mRNA. GO annotations related to this gene include magnesium ion binding and phosphotransferase activity, alcohol group as acceptor. An important paralog of this gene is HK2.

UniProtKB/Swiss-Prot for GCK Gene

  • 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.

Gene Wiki entry for GCK Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GCK Gene

Genomics for GCK Gene

Regulatory Elements for GCK Gene

Enhancers for GCK Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH07F044145 1 ENCODE 9.2 +51.1 51083 2.5 ATF1 PKNOX1 GATA2 KLF13 ZNF263 NCOA1 CREB3 SMARCA4 GLIS1 PBX2 POLD2 GCK LOC105375258 MYL7
GH07F044121 1.1 ENCODE 7.7 +75.1 75131 3.4 HDGF PKNOX1 MLX WRNIP1 ZFP64 ARID4B SIN3A DMAP1 YY1 ZNF143 ENSG00000228680 SNORA5B RPL18AP10 ENSG00000228596 MIR3943 DDX56 SNORA5C NACAD POLR2J4 GCK
GH07F044111 0.9 Ensembl 8.2 +85.2 85213 2.7 GLIS2 SCRT2 CREM EGR2 ZNF202 SP3 ZEB2 SMARCB1 SP1 MBD2 POLM DDX56 MIR6838 SNORA5C ENSG00000228434 SNHG15 SNORA5A SPDYE1 SNORA5B GCK
GH07F044099 1.2 FANTOM5 ENCODE 6.1 +95.2 95152 7.3 ELF3 ATF1 PKNOX1 ARID4B NFXL1 RAD21 GLIS2 SCRT2 FOS ZNF263 POLM AEBP1 MIR6838 GCK RASA4CP
GH07F043673 1.2 Ensembl ENCODE 4.7 +523.9 523893 2.1 PKNOX1 ARNT ZFP64 CBX5 ZNF143 FOS TBX21 PPARG KAT8 MAFF STK17A COA1 LOC100506895 BLVRA URGCP GCK GC07M043624
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around GCK on UCSC Golden Path with GeneCards custom track

Genomic Location for GCK Gene

Chromosome:
7
Start:
44,144,271 bp from pter
End:
44,198,170 bp from pter
Size:
53,900 bases
Orientation:
Minus strand

Genomic View for GCK Gene

Genes around GCK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GCK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GCK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GCK Gene

Proteins for GCK Gene

  • Protein details for GCK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35557-HXK4_HUMAN
    Recommended name:
    Glucokinase
    Protein Accession:
    P35557
    Secondary Accessions:
    • A4D2J2
    • A4D2J3
    • Q05810

    Protein attributes for GCK Gene

    Size:
    465 amino acids
    Molecular mass:
    52191 Da
    Quaternary structure:
    • Monomer.
    Miscellaneous:
    • In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).

    Three dimensional structures from OCA and Proteopedia for GCK Gene

    Alternative splice isoforms for GCK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GCK Gene

Selected DME Specific Peptides for GCK Gene

P35557:
  • EWGAFGD
  • GFTFSFP
  • GVDGSVYK
  • LLRDAIKRR
  • NACYMEE
  • LDLGGTNFRV
  • EGRMCVN
  • LPLGFTFS

Post-translational modifications for GCK Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for GCK Gene

Protein Domains for GCK Gene

Graphical View of Domain Structure for InterPro Entry

P35557

UniProtKB/Swiss-Prot:

HXK4_HUMAN :
  • Contains 1 hexokinase domain.
  • Belongs to the hexokinase family.
Domain:
  • Contains 1 hexokinase domain.
Family:
  • Belongs to the hexokinase family.
genes like me logo Genes that share domains with GCK: view

No data available for Gene Families for GCK Gene

Function for GCK Gene

Molecular function for GCK Gene

GENATLAS Biochemistry:
glucokinase,expressed in liver and islet beta cells of pancreas,glucose specific,primary regulator of glucose-controlled insulin secretion,catalyzing the first step of glycolysis,energy pathway
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + D-glucose = ADP + D-glucose 6-phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
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.
UniProtKB/Swiss-Prot Function:
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.

Enzyme Numbers (IUBMB) for GCK Gene

Gene Ontology (GO) - Molecular Function for GCK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004340 glucokinase activity TAS --
GO:0004396 hexokinase activity IEA --
GO:0005515 protein binding IPI 11522786
GO:0005524 ATP binding IDA 8446612
genes like me logo Genes that share ontologies with GCK: view
genes like me logo Genes that share phenotypes with GCK: view

Human Phenotype Ontology for GCK Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GCK Gene

MGI Knock Outs for GCK:

Animal Model Products

Clone Products

  • Addgene plasmids for GCK

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for GCK Gene

Localization for GCK Gene

Subcellular locations from UniProtKB/Swiss-Prot for GCK Gene

Cytoplasm. Nucleus. Note=Under low glucose concentrations, GCK associates with GKRP and the inactive complex is recruited to the hepatocyte nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GCK gene
Compartment Confidence
nucleus 5
cytosol 5
mitochondrion 4
plasma membrane 2
extracellular 2
peroxisome 2
golgi apparatus 2
endoplasmic reticulum 1
lysosome 1

Gene Ontology (GO) - Cellular Components for GCK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
GO:0005739 mitochondrion IEA --
genes like me logo Genes that share ontologies with GCK: view

Pathways & Interactions for GCK Gene

genes like me logo Genes that share pathways with GCK: view

Gene Ontology (GO) - Biological Process for GCK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001678 cellular glucose homeostasis IBA --
GO:0005975 carbohydrate metabolic process IEA --
GO:0006006 glucose metabolic process IEA --
GO:0006096 glycolytic process IBA --
GO:0006110 regulation of glycolytic process NAS 9570959
genes like me logo Genes that share ontologies with GCK: view

No data available for SIGNOR curated interactions for GCK Gene

Drugs & Compounds for GCK Gene

(57) Drugs for GCK Gene - From: DrugBank, ClinicalTrials, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Glucosamine Approved Nutra 182
Sorbitol Approved Pharma 31
Adenosine triphosphate Approved Nutra 0
Beta-D-Glucose Experimental Pharma Target 0
Glucose 6-phosphate Experimental Pharma 0

(55) Additional Compounds for GCK Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Alpha-D-Glucose
  • a-D-Glucopyranose
  • a-D-Glucose
  • a-Dextrose
  • a-Glucose
  • alpha-D-Glucopyranose
492-62-6
Beta-D-Fructose 6-phosphate
  • beta-D-Fructose 6-phosphate
dADP
  • 2'-Deoxyadenosine-5'-diphosphate
  • dADP
  • Deoxyadenosine diphosphate
2793-06-8
D-Glucose
  • Roferose ST
  • (+)-Glucose
  • Anhydrous dextrose
  • Cerelose
  • Cerelose 2001
50-99-7

(2) ApexBio Compounds for GCK Gene

Compound Action Cas Number
LY2608204 GK activator 1234703-40-2
Ro 28-1675 Glucokinase activator 300353-13-3
genes like me logo Genes that share compounds with GCK: view

Transcripts for GCK Gene

Unigene Clusters for GCK Gene

Glucokinase (hexokinase 4):
Representative Sequences:

Clone Products

  • Addgene plasmids for GCK

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for GCK Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b · 11c ^ 12 ^ 13a · 13b · 13c · 13d · 13e · 13f ^ 14
SP1: - - -
SP2: - - - - - -
SP3: - - - -
SP4: - - - - -
SP5: -
SP6:
SP7:

Relevant External Links for GCK Gene

GeneLoc Exon Structure for
GCK
ECgene alternative splicing isoforms for
GCK

Expression for GCK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GCK Gene

mRNA differential expression in normal tissues according to GTEx for GCK Gene

This gene is overexpressed in Pituitary (x15.5).

Protein differential expression in normal tissues from HIPED for GCK Gene

This gene is overexpressed in Liver (44.7) and Fetal heart (24.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for GCK Gene



Protein tissue co-expression partners for GCK Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of GCK Gene:

GCK

SOURCE GeneReport for Unigene cluster for GCK Gene:

Hs.1270

mRNA Expression by UniProt/SwissProt for GCK Gene:

P35557-HXK4_HUMAN
Tissue specificity: Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver.
genes like me logo Genes that share expression patterns with GCK: view

Orthologs for GCK Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for GCK Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GCK 34 35
  • 99.56 (n)
dog
(Canis familiaris)
Mammalia GCK 35
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GCK 35
  • 92 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GCK 34 35
  • 91.25 (n)
mouse
(Mus musculus)
Mammalia Gck 34 16 35
  • 89.03 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia GCK 35
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gck 34
  • 87.38 (n)
chicken
(Gallus gallus)
Aves GCK 34 35
  • 85.28 (n)
lizard
(Anolis carolinensis)
Reptilia GCK 35
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gck 34
  • 72.63 (n)
African clawed frog
(Xenopus laevis)
Amphibia gck-A 34
zebrafish
(Danio rerio)
Actinopterygii gck 34 35
  • 75.07 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11643 34
fruit fly
(Drosophila melanogaster)
Insecta Hex-A 36 35
  • 47 (a)
Hex-C 36 35
  • 43 (a)
Hex-t2 36 35
  • 41 (a)
Hex-t1 36
  • 31 (a)
worm
(Caenorhabditis elegans)
Secernentea F14B4.2 36 35
  • 45 (a)
H25P06.1 36
  • 40 (a)
Y77E11A.1 36
  • 32 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HXK1 35
  • 31 (a)
ManyToMany
HXK2 35
  • 28 (a)
ManyToMany
EMI2 35
  • 27 (a)
ManyToMany
GLK1 35
  • 27 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.11095 35
  • 46 (a)
OneToMany
Species where no ortholog for GCK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GCK Gene

ENSEMBL:
Gene Tree for GCK (if available)
TreeFam:
Gene Tree for GCK (if available)

Paralogs for GCK Gene

Variants for GCK Gene

Sequence variations from dbSNP and Humsavar for GCK Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type
rs104894005 Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851], Pathogenic 44,147,678(-) TGGAC(C/G/T)AGAGC nc-transcript-variant, reference, missense, stop-gained
rs104894008 Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851], Pathogenic 44,147,732(-) CCTTC(A/G)GGGAC nc-transcript-variant, reference, missense
rs104894009 Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851], Pathogenic 44,146,587(-) ACATG(C/G)GCGAG upstream-variant-2KB, reference, missense
rs104894010 Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851], Pathogenic 44,151,048(-) GCATC(C/T)CCGAC reference, missense
rs104894012 Familial hyperinsulinemic hypoglycemia 3 (HHF3) [MIM:602485], Pathogenic 44,145,171(-) CGGCG(A/G)TGGCC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for GCK Gene

Variant ID Type Subtype PubMed ID
nsv1120544 CNV tandem duplication 24896259
nsv428165 CNV gain 18775914
nsv509195 CNV insertion 20534489
nsv8082 CNV gain 18304495
nsv830983 CNV loss 17160897

Variation tolerance for GCK Gene

Residual Variation Intolerance Score: 7.53% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.34; 7.54% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for GCK Gene

Human Gene Mutation Database (HGMD)
GCK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GCK

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GCK Gene

Disorders for GCK Gene

MalaCards: The human disease database

(28) MalaCards diseases for GCK Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hyperinsulinemic hypoglycemia, familial, 3
  • hyperinsulinemic hypoglycemia familial 3
mody, type ii
  • maturity-onset diabetes of the young, type 2
diabetes mellitus, permanent neonatal
  • diabetes, permanent neonatal
maturity-onset diabetes of the young
  • mason-type diabetes
gestational diabetes
  • gdm
- elite association - COSMIC cancer census association via MalaCards
Search GCK in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HXK4_HUMAN
  • Familial hyperinsulinemic hypoglycemia 3 (HHF3) [MIM:602485]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. {ECO:0000269 PubMed:9435328}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851]: 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. {ECO:0000269 PubMed:10588527, ECO:0000269 PubMed:10694920, ECO:0000269 PubMed:11106831, ECO:0000269 PubMed:11372010, ECO:0000269 PubMed:1303265, ECO:0000269 PubMed:1464666, ECO:0000269 PubMed:1502186, ECO:0000269 PubMed:22611063, ECO:0000269 PubMed:8168652, ECO:0000269 PubMed:8325892, ECO:0000269 PubMed:8495817, ECO:0000269 PubMed:9049484, ECO:0000269 PubMed:9662401}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for GCK

Genetic Association Database (GAD)
GCK
Human Genome Epidemiology (HuGE) Navigator
GCK
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
GCK
genes like me logo Genes that share disorders with GCK: view

No data available for Genatlas for GCK Gene

Publications for GCK Gene

  1. Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus. (PMID: 11106831) Nam J.H. … Huh K.B. (Diabetes Res. Clin. Pract. 2000) 3 4 22 46 64
  2. Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non- insulin-dependent (type 2) diabetes mellitus. (PMID: 1502186) Stoffel M. … Bell G.I. (Proc. Natl. Acad. Sci. U.S.A. 1992) 2 3 4 46 64
  3. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. (PMID: 20164212) Flanagan S.E. … Ellard S. (Eur. J. Endocrinol. 2010) 3 22 46 64
  4. The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits. (PMID: 19018513) Webster R.J. … Frayling T.M. (Diabetologia 2009) 3 22 46 64
  5. Interaction effect of genetic polymorphisms in glucokinase (GCK) and glucokinase regulatory protein (GCKR) on metabolic traits in healthy Chinese adults and adolescents. (PMID: 19073768) Tam C.H. … Ng M.C. (Diabetes 2009) 3 22 46 64

Products for GCK Gene

Sources for GCK Gene