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    GCK glucokinase [ Homo sapiens (human) ]

    Gene ID: 2645, updated on 20-Jun-2021

    Summary

    Official Symbol
    GCKprovided by HGNC
    Official Full Name
    glucokinaseprovided by HGNC
    Primary source
    HGNC:HGNC:4195
    See related
    Ensembl:ENSG00000106633 MIM:138079
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GK; GLK; HK4; HHF3; HKIV; HXKP; LGLK; MODY2; PNDM1; FGQTL3
    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. [provided by RefSeq, Aug 2017]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See GCK in Genome Data Viewer
    Location:
    7p13
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 7 NC_000007.14 (44143213..44189439, complement)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (44182812..44229038, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene RNA, 5S ribosomal pseudogene 230 Neighboring gene uncharacterized LOC105375258 Neighboring gene myosin light chain 7 Neighboring gene uncharacterized LOC105375257 Neighboring gene YKT6 v-SNARE homolog Neighboring gene calcium/calmodulin dependent protein kinase II beta

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
    GeneReviews: Not available
    A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.
    GeneReviews: Not available
    Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathways.
    GeneReviews: Not available
    Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
    GeneReviews: Not available
    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.
    GeneReviews: Not available
    Hyperinsulinism due to glucokinase deficiency
    MedGen: C1865290 OMIM: 602485 GeneReviews: Familial Hyperinsulinism
    Compare labs
    Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.
    GeneReviews: Not available
    Maturity-onset diabetes of the young, type 2 Compare labs
    Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.
    GeneReviews: Not available
    New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
    GeneReviews: Not available
    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.
    GeneReviews: Not available
    Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study.
    GeneReviews: Not available
    Permanent neonatal diabetes mellitus Compare labs
    Permanent neonatal diabetes mellitus 1 Compare labs
    Type 2 diabetes mellitus
    MedGen: C0011860 OMIM: 125853 GeneReviews: Not available
    Compare labs
    Variants in MTNR1B influence fasting glucose levels.
    GeneReviews: Not available

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of glucokinase (hexokinase 4) (GCK) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Pr55(Gag) gag The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with GCK PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables fructokinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables glucokinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables glucokinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables glucokinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables glucose binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables mannokinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in NADP metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in calcium ion import IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in canonical glycolysis TAS
    Traceable Author Statement
    more info
     
    involved_in carbohydrate phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular glucose homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in cellular response to insulin stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to leptin stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in detection of glucose IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in glucose 6-phosphate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in glucose 6-phosphate metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in glucose homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in glycolytic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in negative regulation of gluconeogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of glycogen biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of insulin secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of glycolytic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of glycolytic process TAS
    Traceable Author Statement
    more info
     
    involved_in regulation of insulin secretion IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in regulation of insulin secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of potassium ion transport IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    hexokinase-4
    Names
    ATP:D-hexose 6-phosphotransferase
    HK IV
    glucokinase (hexokinase 4)
    hexokinase D, pancreatic isozyme
    hexokinase type IV
    NP_000153.1
    NP_001341729.1
    NP_001341730.1
    NP_001341731.1
    NP_001341732.1
    NP_277042.1
    NP_277043.1
    XP_024302475.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008847.2 RefSeqGene

      Range
      13732..58896
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1074

    mRNA and Protein(s)

    1. NM_000162.5NP_000153.1  hexokinase-4 isoform 1

      See identical proteins and their annotated locations for NP_000153.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the isoform expressed specifically in pancreatic islet beta cells. Its first exon is specific to this variant, which has a unique 5' UTR. Isoform 1 has a distinct N-terminus; the remainder of the protein is identical to isoforms 2 and 3.
      Source sequence(s)
      AC006454, BC001890
      Consensus CDS
      CCDS5479.1
      UniProtKB/Swiss-Prot
      P35557
      UniProtKB/TrEMBL
      Q53Y25
      Related
      ENSP00000384247.3, ENST00000403799.8
      Conserved Domains (2) summary
      COG5026
      Location:8458
      COG5026; Hexokinase [Carbohydrate transport and metabolism]
      pfam00349
      Location:15215
      Hexokinase_1
    2. NM_001354800.1NP_001341729.1  hexokinase-4 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC006454
      Related
      ENSP00000499852.1, ENST00000673284.1
      Conserved Domains (2) summary
      COG5026
      Location:8456
      COG5026; Hexokinase [Carbohydrate transport and metabolism]
      pfam00349
      Location:15215
      Hexokinase_1
    3. NM_001354801.1NP_001341730.1  hexokinase-4 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC006454, M90299
      Related
      ENST00000683378.1
      Conserved Domains (1) summary
      pfam03727
      Location:2118
      Hexokinase_2
    4. NM_001354802.1NP_001341731.1  hexokinase-4 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC006454
      Conserved Domains (1) summary
      pfam03727
      Location:175
      Hexokinase_2
    5. NM_001354803.2NP_001341732.1  hexokinase-4 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC006454, M90299
      Related
      ENSP00000338009.5, ENST00000336642.9
      Conserved Domains (1) summary
      pfam03727
      Location:19133
      Hexokinase_2
    6. NM_033507.3NP_277042.1  hexokinase-4 isoform 2

      See identical proteins and their annotated locations for NP_277042.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the major isoform expressed in liver. Its first exon is specific to the liver transcripts, variants 2 and 3, but it lacks a second liver-specific exon found in variant 3. Isoform 2 has a distinct N-terminus; the remainder of the protein is identical to isoforms 1 and 3.
      Source sequence(s)
      AK122876, CD251038, M69051, M90299
      Consensus CDS
      CCDS5480.1
      UniProtKB/Swiss-Prot
      P35557
      Related
      ENSP00000223366.2, ENST00000345378.7
      Conserved Domains (2) summary
      COG5026
      Location:17459
      COG5026; Hexokinase [Carbohydrate transport and metabolism]
      pfam00349
      Location:17216
      Hexokinase_1
    7. NM_033508.3NP_277043.1  hexokinase-4 isoform 3

      See identical proteins and their annotated locations for NP_277043.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is the minor form expressed in liver. Its first exon is specific to the liver transcripts, variants 2 and 3; its second exon is unique to this transcript. Isoform 3 has a distinct N-terminus; the remainder of the protein is identical to isoforms 1 and 2.
      Source sequence(s)
      AK122876, CD251038, DA640823, M69051, M90299
      UniProtKB/Swiss-Prot
      P35557
      Conserved Domains (2) summary
      COG5026
      Location:13457
      COG5026; Hexokinase [Carbohydrate transport and metabolism]
      pfam00349
      Location:14214
      Hexokinase_1

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p13 Primary Assembly

      Range
      44143213..44189439 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024446707.1XP_024302475.1  hexokinase-4 isoform X1

      Conserved Domains (1) summary
      pfam03727
      Location:175
      Hexokinase_2
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