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GCK Gene

protein-coding   GIFtS: 74
GCID: GC07M044183

Glucokinase (Hexokinase 4)

(Previous name: maturity onset diabetes of the young 2)
(Previous symbol: MODY2)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Glucokinase (Hexokinase 4)1 2     HXKP2
MODY21 2     LGLK2
Hexokinase Type IV2 3     ATP:D-Hexose 6-Phosphotransferase2
HK42 3     glucokinase2
HK IV2 3     Hexokinase D, Pancreatic Isozyme2
HHF32 5     hexokinase-42
Maturity Onset Diabetes Of The Young 21     hexokinase-D2
FGQTL32     EC 2.7.1.23
GK2     Hexokinase-43
GLK2     Hexokinase-D3
HKIV2     EC 2.7.18

External Ids:    HGNC: 41951   Entrez Gene: 26452   Ensembl: ENSG000001066337   OMIM: 1380795   UniProtKB: P355573   

Export aliases for GCK gene to outside databases

Previous GC identifers: GC07M043830 GC07M043890 GC07M043924 GC07M043957 GC07M044150 GC07M044070


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 (hexokinase 4)) is a protein-coding gene. Diseases associated with GCK include gestational diabetes, and maturity-onset diabetes of the young. GO annotations related to this gene include ADP binding and magnesium ion binding. An important paralog of this gene is HK3.

UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557
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

Gene Wiki entry for GCK (Glucokinase) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000007.14  NC_018918.2  NT_007819.18  
Regulatory elements:
   Regulatory transcription factor binding sites in the GCK gene promoter:
         AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): GCK promoter sequence
   Search Chromatin IP Primers for GCK

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GCK


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7p15.3-p15.1   Ensembl cytogenetic band:  7p13   HGNC cytogenetic band: 7p15.3-p15.1

GCK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GCK gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07M044183:  view genomic region     (about GC identifiers)

Start:
44,183,870 bp from pter      End:
44,237,769 bp from pter
Size:
53,900 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 44,223,370-44,268,527     

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557 (See protein sequence)
Recommended Name: Glucokinase  
Size: 465 amino acids; 52191 Da
Subunit: Monomer
Miscellaneous: In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I,
II, III and IV (glucokinase)
Selected PDB 3D structures from and Proteopedia for GCK (see all 28):
1GLK (3D)        1V4S (3D)        1V4T (3D)        3A0I (3D)        3F9M (3D)        3FGU (3D)    
Secondary accessions: A4D2J2 A4D2J3 Q05810
Alternative splicing: 3 isoforms:  P35557-1   P35557-2   P35557-3   

Explore the universe of human proteins at neXtProt for GCK: NX_P35557

Explore proteomics data for GCK at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for GCK (P35557) (see all 8)
     EWGAFGD  EGRMCVN  GFTFSFP  NACYMEE 


    See GCK Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_000153.1  NP_277042.1  NP_277043.1  

    ENSEMBL proteins: 
     ENSP00000338009   ENSP00000384247   ENSP00000379142   ENSP00000223366   ENSP00000402840  
    Reactome Protein details: P35557

    GCK Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for GCK (Glucokinase/GCK)
    Enzo Life Sciences proteins for GCK
    OriGene Purified Proteins for GCK
    OriGene Protein Over-expression Lysate for GCK
    OriGene MassSpec for GCK
    OriGene Custom Protein Services for GCK
    GenScript Custom Purified and Recombinant Proteins Services for GCK
    Novus Biologicals GCK Proteins
    Novus Biologicals GCK Lysates
    Sino Biological Recombinant Protein for GCK
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for GCK
    Cloud-Clone Corp. Proteins for GCK

    GCK Antibody Products:

    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
    R&D Systems Antibodies for GCK (Glucokinase/GCK)
    OriGene Antibodies for GCK
    OriGene Custom Antibody Services for GCK
    Novus Biologicals GCK Antibodies
    Abcam antibodies for GCK
    Cloud-Clone Corp. Antibodies for GCK
    ThermoFisher Antibody for GCK
    LSBio Antibodies in human, mouse, rat for GCK

    GCK Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for GCK
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for GCK
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for GCK
    Cloud-Clone Corp. CLIAs for GCK


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR019807 Hexokinase_CS
     IPR001312 Hexokinase
     IPR022672 Hexokinase_N
     IPR022673 Hexokinase_C

    Graphical View of Domain Structure for InterPro Entry P35557

    ProtoNet protein and cluster: P35557

    1 Blocks protein domain: IPB001312 Hexokinase

    UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557
    Similarity: Belongs to the hexokinase family
    Similarity: Contains 1 hexokinase type-1 domain
    Similarity: Contains 1 hexokinase type-2 domain


    GCK for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: HXK4_HUMAN, P35557
    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
    Catalytic activity: ATP + D-glucose = ADP + D-glucose 6-phosphate
    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

         Genatlas biochemistry entry for GCK:
    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

         Enzyme Numbers (IUBMB): EC 2.7.1.21 EC 2.7.12

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287magnesium ion binding IEA--
    GO:0004340glucokinase activity IDA12941786
    GO:0004396hexokinase activity ----
    GO:0005515protein binding IPI11522786
    GO:0005524ATP binding IDA12941786
         
    GCK for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for GCK:
     Decreased p24 protein expressi  Decreased viability with TRAIL 

         7 MGI mutant phenotypes (inferred from 26 alleles(MGI details for Gck):
     endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism  liver/biliary system 
     mortality/aging  renal/urinary system 

    GCK for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for GCK: Gcktm1.2Mgn Gcktm1Tka Gcktm1Ts Gcktm1Efr

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for GCK
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for GCK

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for GCK
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for GCK

    miRNA
    Products:
        
    miRTarBase miRNAs that target GCK:
    hsa-mir-335-5p (MIRT018730)

    Block miRNA regulation of human, mouse, rat GCK using miScript Target Protectors
    3 qRT-PCR Assays for microRNAs that regulate GCK:
    hsa-miR-4324 hsa-miR-4253 hsa-miR-544b
    SwitchGear 3'UTR luciferase reporter plasmidGCK 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for GCK
    Predesigned siRNA for gene silencing in human, mouse, rat GCK

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for GCK

    Clone
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    OriGene clones in human, mouse for GCK (see all 18)
    OriGene ORF clones in mouse, rat for GCK
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): GCK (NM_000162)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for GCK
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat GCK

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for GCK
    Browse ESI BIO Cell Lines and PureStem Progenitors for GCK 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GCK


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    nucleus4
    extracellular2
    golgi apparatus2
    mitochondrion2
    peroxisome2
    plasma membrane2
    endoplasmic reticulum1
    lysosome1

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus ----
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm ----
    GO:0005739mitochondrion IEA--
    GO:0005829cytosol TAS--

    GCK for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for GCK About   (see all 22)  
    See pathways by source

    SuperPathContained pathways About
    1Glycolysis and gluconeogenesis short map
    Glycolysis and gluconeogenesis short map 0.60
    Glycolysis / Gluconeogenesis0.46
    Glycolysis and Gluconeogenesis0.60
    glycolysis0.00
    2Regulation of beta-cell development
    Regulation of beta-cell development0.64
    Maturity onset diabetes of the young0.61
    Regulation of gene expression in beta cells0.64
    3Galactose metabolism
    Galactose metabolism0.44
    Butirosin and neomycin biosynthesis0.00
    Galactose metabolism0.44
    4Glucuronidation
    Starch and sucrose metabolism0.41
    Glycogen metabolism0.00
    5Type II diabetes mellitus
    Type II diabetes mellitus0.38
    Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics0.38

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for GCK
        MODY (Maturity-Onset Diabetes of Young)

    3 GeneGo (Thomson Reuters) Pathways for GCK
        Galactose metabolism
    Glycogen metabolism
    Glycolysis and gluconeogenesis (short map)

    Selected BioSystems Pathways for GCK (see all 11)
        MAPK signaling pathway
    SIDS Susceptibility Pathways
    GDP-glucose biosynthesis
    Glycolysis and Gluconeogenesis
    glycolysis


    3 Reactome Pathways for GCK
        Regulation of Glucokinase by Glucokinase Regulatory Protein
    Regulation of gene expression in beta cells
    Glucose transport

    1 PharmGKB Pathway for GCK
        Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics

    Selected Kegg Pathways  (Kegg details for GCK) (see all 12):
        Glycolysis / Gluconeogenesis
    Galactose metabolism
    Starch and sucrose metabolism
    Amino sugar and nucleotide sugar metabolism
    Butirosin and neomycin biosynthesis


    GCK for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including GCK: 
              Insulin Signaling Pathway in human mouse rat
              Fatty Liver in human mouse rat
              Diabetes in human mouse rat
              Glucose Metabolism in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for GCK

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for GCK (P355571, 3 ENSP000002233664) via UniProtKB, MINT, STRING, and/or I2D (see all 47)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    GCKRQ143971, 3, ENSP000002647174EBI-709928,EBI-709948 I2D: score=4 STRING: ENSP00000264717
    PFKFB1P161181, 3, ENSP000003641454EBI-709928,EBI-709807 I2D: score=1 STRING: ENSP00000364145
    BADQ929343, ENSP000003091034I2D: score=1 STRING: ENSP00000309103
    GLUD1P003673, ENSP000002778654I2D: score=1 STRING: ENSP00000277865
    PFKFB2O608253, ENSP000003560474I2D: score=2 STRING: ENSP00000356047
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 33):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001678cellular glucose homeostasis IBA--
    GO:0005975carbohydrate metabolic process TAS--
    GO:0005978glycogen biosynthetic process IEA--
    GO:0006003fructose 2,6-bisphosphate metabolic process IEA--
    GO:0006006glucose metabolic process ----

    GCK for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for GCK (HXK4)

    Selected HMDB Compounds for GCK (see all 18)    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Alpha-D-GlucoseHexopyranose (see all 11)492-62-6--
    Beta-D-Fructose 6-phosphatebeta-D-Fructose 6-phosphate (see all 2)----
    Beta-D-Glucoseb-D-Glucopyranose (see all 8)492-61-5--
    Beta-D-Glucose 6-phosphatebeta-D-glucose 6-(dihydrogen phosphate) (see all 3)----
    D-Glucose(+)-Glucose (see all 23)50-99-7--
    D-MannoseDL-mannose (see all 13)3458-28-4--
    Glucosamine2-Amino-2-deoxy-D-glucopyranose (see all 10)3416-24-8--
    Glucosamine 6-phosphate2-Amino-2-deoxy-D-glucose 6-phosphate (see all 14)3616-42-0--

    5 DrugBank Compounds for GCK    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Beta-D-Glucose-- 50-99-7target--17139284 17016423
    2-(methylamino)-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide-- --target--10592235
    2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE-- --target--10592235
    2-amino-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide-- --target--10592235
    3-[(4-fluorophenyl)sulfanyl]-N-(4-methyl-1,3-thiazol-2-yl)-6-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carboxamide-- --target--10592235

    Selected Novoseek inferred chemical compound relationships for GCK gene (see all 85)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    mannoheptulose 88 31 10677361 (4), 15202024 (2), 7614462 (2), 9762360 (1) (see all 17)
    glucose 83.9 1226 1612193 (10), 10677361 (9), 9762360 (7), 12101177 (7) (see all 99)
    fructose 1-phosphate 83.3 18 9762360 (3), 9003425 (3), 10677361 (2), 9230355 (1) (see all 10)
    glucose 6-phosphate 77 90 16403021 (7), 10455119 (4), 12765941 (3), 9325299 (2) (see all 45)
    fructose-6-phosphate 70.7 14 14627435 (2), 10455119 (2), 9230355 (1), 18556336 (1) (see all 9)
    glycogen 66.9 148 11600496 (8), 18165236 (6), 8878425 (6), 16403021 (5) (see all 38)
    preproinsulin 64.7 9 11319727 (2), 14563207 (2), 15148392 (1)
    d-(5-3h)glucose 62.1 1 11739021 (1)
    katp 62 13 17380317 (2), 14641012 (1), 15350960 (1), 17179930 (1) (see all 10)
    sulfonylurea 61.1 15 10459863 (4), 11289470 (3), 9166666 (1), 15579781 (1) (see all 8)



    GCK for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for GCK gene (3 alternative transcripts): 
    NM_000162.3  NM_033507.1  NM_033508.1  

    Unigene Cluster for GCK:

    Glucokinase (hexokinase 4)
    Hs.1270  [show with all ESTs]
    Unigene Representative Sequence: BC001890
    8 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000459642 ENST00000336642 ENST00000403799(uc003tkl.2) ENST00000395796(uc003tkj.1)
    ENST00000345378(uc003tkk.1) ENST00000437084 ENST00000473353 ENST00000476008

    miRNA
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    Block miRNA regulation of human, mouse, rat GCK using miScript Target Protectors
    3 qRT-PCR Assays for microRNAs that regulate GCK:
    hsa-miR-4324 hsa-miR-4253 hsa-miR-544b
    SwitchGear 3'UTR luciferase reporter plasmidGCK 3' UTR sequence
    Inhib. RNA
    Products:
         
    OriGene RNAi products in human, mouse, rat for GCK
    Predesigned siRNA for gene silencing in human, mouse, rat GCK
    Clone
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    OriGene clones in human, mouse for GCK (see all 18)
    OriGene ORF clones in mouse, rat for GCK
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): GCK (NM_000162)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for GCK
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat GCK
    Primer
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    OriGene qPCR primer pairs and template standards for GCK
    OriGene qSTAR qPCR primer pairs in human, mouse for GCK
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat GCK
      QuantiTect SYBR Green Assays in human, mouse, rat GCK
      QuantiFast Probe-based Assays in human, mouse, rat GCK

    Additional mRNA sequence: 

    AK122876.1 BC001890.1 BT007062.1 EU008605.1 M69051.1 M88011.1 M90299.1 

    6 DOTS entries:

    DT.112070  DT.100750248  DT.91675210  DT.100811067  DT.91908034  DT.99993532 

    Selected AceView cDNA sequences (see all 48):

    F08353 BC001890 CR590130 NM_033508 AK122876 CR626628 M88011 NM_000162 
    BM966913 CK823298 NM_033507 F04579 M90299 CA405747 CD251038 AW118085 
    BE799829 BX413251 BM966889 AW248814 BE264512 BE796959 M69051 BQ424932 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for GCK (see all 7)    About this scheme

    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:                                                                                -                                                   


    ECgene alternative splicing isoforms for GCK

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    GCK expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CCCAACCTAA
    GCK Expression
    About this image


    GCK expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Pancreas (Endocrine System)    fully expand to see all 3 entries
             Pancreatic-like islets
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Brain (Nervous System)
             Cerebellum
     
     Liver (Hepatobiliary System)
    GCK Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    GCK Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.1270

    UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557
    Tissue specificity: Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver

        Pathway & Disease-focused RT2 Profiler PCR Arrays including GCK: 
              Insulin Signaling Pathway in human mouse rat
              Fatty Liver in human mouse rat
              Diabetes in human mouse rat
              Glucose Metabolism in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for GCK gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Gck1 , 5 glucokinase1, 5 89.03(n)1
    95.91(a)1
      11 (3.88 cM)5
    1039881  NM_010292.41  NP_034422.21 
     59008205 
    chicken
    (Gallus gallus)
    Aves GCK1 glucokinase (hexokinase 4) 85.28(n)
    90.29(a)
      430370  XM_427930.4  XP_427930.4 
    lizard
    (Anolis carolinensis)
    Reptilia GCK6
    glucokinase (hexokinase 4)
    86(a)
    1 ↔ 1
    GL343238.1(356106-379706)
    African clawed frog
    (Xenopus laevis)
    Amphibia gck-A2 glucokinase 78.84(n)    X93494.1 
    zebrafish
    (Danio rerio)
    Actinopterygii gck1 glucokinase (hexokinase 4, maturity onset diabetes more 75.07(n)
    83.71(a)
      751668  NM_001045385.2  NP_001038850.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta Hex-A3 hexokinase 47(a)
    (best of 4)
      1 8E10   --
    worm
    (Caenorhabditis elegans)
    Secernentea F14B4.23 hexokinase 45(a)
    (best of 3)
      I(9279949-9281838)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes HXK16
    HXK26
    (see all 4)
    Hexokinase isoenzyme 1, a cytosolic protein that c...
    Hexokinase isoenzyme 2 that catalyzes phosphorylat...
    (see all 4)
    31(a)
    28(a)
    (see all 4)
    many ↔ many
    many ↔ many
    (see all 4)
    VI(253592-255049) YFR053C
    VII(23935-25395) YGL253W


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for GCK gene
    HK32  HKDC12  HK22  HK12  
    5 SIMAP similar genes for GCK using alignment to 17 protein entries:     HXK4_HUMAN (see all proteins):
    HK2    DKFZp686M1669    HKDC1    HK1    HK3

    GCK for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for GCK (see all 1156)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1048940051,2,,4
    C,FMaturity-onset diabetes of the young 2 (MODY2)4 pathogenic144162779(-) TGGACC/G/TAGAGC 6 E * stg11NA 4550
    VAR_0037114
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0037112 E Q mis40--------
    VAR_0105864
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0105862 Y H mis40--------
    VAR_0105984
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0105982 A T mis40--------
    VAR_0036974
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0036972 S P mis40--------
    VAR_0123504
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0123502 L P mis40--------
    VAR_0036934
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0036932 E K mis40--------
    VAR_0037024
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0037022 E K mis40--------
    VAR_0037104
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0037102 G R mis40--------
    VAR_0036994
    Maturity-onset diabetes of the young 2 (MODY2)4--see VAR_0036992 V M mis40--------

    HapMap Linkage Disequilibrium report for GCK (44183870 - 44237769 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for GCK:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv509195CNV Insertion20534489
    nsv887996CNV Loss21882294
    nsv830983CNV Loss17160897
    nsv428165CNV Gain18775914
    nsv8082CNV Gain18304495

    Human Gene Mutation Database (HGMD): GCK
    Locus Specific Mutation Databases (LSDB): GCK

    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing GCK
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 138079   
    OMIM disorders: 125851  125853  602485  606176  
    UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557
  • 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.
    Note=The disease is caused by mutations affecting the gene represented in this entry
  • 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. Note=The disease is caused by mutations affecting the gene represented in
    this entry

  • Selected diseases for GCK (see all 54):    
    About MalaCards
    gestational diabetes    maturity-onset diabetes of the young    hyperinsulinemic hypoglycemia familial 3    gck-related hyperinsulinism
    permanent neonatal diabetes mellitus    chromosome 7p deletion    maturity-onset diabetes of the young, type 2    gck-related permanent neonatal diabetes mellitus
    diabetes mellitus, noninsulin-dependent, late onset    hypoglycemia    monogenic diabetes    familial hyperinsulinism
    leucine-sensitive hypoglycemia of infancy    hyperinsulinism    hyperglycemia    hyperinsulinemic hypoglycemia
    diabetes mellitus    greig cephalopolysyndactyly syndrome    3-hydroxyacyl-coa dehydrogenase deficiency    pancreatic agenesis

    7 diseases from the University of Copenhagen DISEASES database for GCK:
    maturity-onset diabetes of the young     Diabetes mellitus     Hyperglycemia     Hyperinsulinism
    Hypoglycemia     Hyperinsulinemic hypoglycemia     Insulinoma

    GCK for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for GCK gene (see all 28)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    niddm 87 225 8349034 (5), 8433729 (5), 9653619 (3), 1545870 (3) (see all 99)
    neonatal diabetes mellitus 79.2 11 18571549 (2), 14517946 (1), 16602010 (1), 19496967 (1) (see all 7)
    hyperglycemia 77.9 110 9049484 (4), 8720607 (3), 19309449 (3), 8826967 (3) (see all 52)
    hyperinsulinism 73.1 29 19053014 (4), 19336674 (4), 18450771 (2), 14641012 (1) (see all 11)
    hypoglycemia 65.8 54 14517946 (4), 15277402 (4), 19790256 (4), 19336674 (2) (see all 24)
    neonatal hypoglycemia 64.7 1 19884385 (1)
    impaired glucose tolerance 64.5 11 9653619 (1), 9049484 (1), 19564454 (1), 15983230 (1) (see all 7)
    insulinoma 64.1 18 9325299 (3), 9166666 (2), 9113996 (2), 2185104 (1) (see all 11)
    diabetes mellitus 62.2 24 8495817 (1), 10694920 (1), 18382660 (1), 19551638 (1) (see all 21)
    insulin resistance 56 10 8720607 (2), 8712800 (1), 18406764 (1), 11289470 (1) (see all 8)

    GeneTests: GCK
    GeneReviews: GCK
    Genetic Association Database (GAD): GCK
    Human Genome Epidemiology (HuGE) Navigator: GCK (80 documents)

    Export disorders for GCK gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for GCK gene, integrated from 10 sources (see all 742):
    (articles sorted by number of sources associating them with GCK)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non- insulin-dependent (type 2) diabetes mellitus. (PubMed id 1502186)1, 2, 3, 4, 9 Stoffel M.... Bell G.I. (Proc. Natl. Acad. Sci. U.S.A. 1992)
    2. Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus. (PubMed id 11106831)1, 2, 4, 9 Nam J.H....Huh K.B. (Diabetes Res. Clin. Pract. 2000)
    3. Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation. (PubMed id 18450771)1, 4, 9 Christesen H.B....Gloyn A.L. (Eur. J. Endocrinol. 2008)
    4. Interaction effect of genetic polymorphisms in glucokinase (GCK) and glucokinase regulatory protein (GCKR) on metabolic traits in healthy Chinese adults and adolescents. (PubMed id 19073768)1, 4, 9 Tam C.H....Ng M.C. (Diabetes 2009)
    5. Additive effects of genetic variation in GCK and G6PC2 on insulin secretion and fasting glucose. (PubMed id 19741163)1, 4, 9 Li X....Watanabe R.M. (Diabetes 2009)
    6. Characterization of glucokinase polymorphisms associated with maturity-onset diabetes of the young (MODY2) in Jordanian population. (PubMed id 20458967)1, 4, 9 Al-Sheyab F....Khaul R.W. (Tsitol. Genet. 2009)
    7. Screening of mutations and polymorphisms in the glucokinase gene in Czech diabetic and healthy control populations. (PubMed id 18271687)1, 4, 9 LukA!sovA! P....BendlovA! B. (Physiol Res 2008)
    8. Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk. (PubMed id 19533084)1, 4, 9 Reiling E....'t Hart L.M. (Diabetologia 2009)
    9. Maturity-onset diabetes of the young in children with incidental hyperglycemia: a multicenter Italian study of 172 families. (PubMed id 19564454)1, 4, 9 Lorini R....Barbetti F. (Diabetes Care 2009)
    10. A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses. (PubMed id 17186458)1, 4, 9 Weedon M.N....Frayling T.M. (Am. J. Hum. Genet. 2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2645 HGNC: 4195 AceView: GCK Ensembl:ENSG00000106633 euGenes: HUgn2645
    ECgene: GCK Kegg: 2645 H-InvDB: GCK

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for GCK Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=GCK[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/Glucokinase

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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    Patent Information for GCK gene:
    Search GeneIP for patents involving GCK

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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