LOCUS       NM_000162               2745 bp    mRNA    linear   PRI 04-DEC-2024
DEFINITION  Homo sapiens glucokinase (GCK), transcript variant 1, mRNA.
ACCESSION   NM_000162
VERSION     NM_000162.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2745)
  AUTHORS   Lahnsteiner,A., Ellmer,V., Oberlercher,A., Liutkeviciute,Z.,
            Schonauer,E., Paulweber,B., Aigner,E. and Risch,A.
  TITLE     G-quadruplex forming regions in GCK and TM6SF2 are targets for
            differential DNA methylation in metabolic disease and
            hepatocellular carcinoma patients
  JOURNAL   Sci Rep 14 (1), 20215 (2024)
   PUBMED   39215018
  REMARK    GeneRIF: G-quadruplex forming regions in GCK and TM6SF2 are targets
            for differential DNA methylation in metabolic disease and
            hepatocellular carcinoma patients.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2745)
  AUTHORS   Gersing,S., Schulze,T.K., Cagiada,M., Stein,A., Roth,F.P.,
            Lindorff-Larsen,K. and Hartmann-Petersen,R.
  TITLE     Characterizing glucokinase variant mechanisms using a multiplexed
            abundance assay
  JOURNAL   Genome Biol 25 (1), 98 (2024)
   PUBMED   38627865
  REMARK    GeneRIF: Characterizing glucokinase variant mechanisms using a
            multiplexed abundance assay.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2745)
  AUTHORS   Wang,T., Zhu,M., Wang,Y., Hu,C., Fang,C. and Hu,J.
  TITLE     Two novel GCK mutations in Chinese patients with maturity-onset
            diabetes of the young
  JOURNAL   Endocrine 83 (1), 92-98 (2024)
   PUBMED   37847371
  REMARK    GeneRIF: Two novel GCK mutations in Chinese patients with
            maturity-onset diabetes of the young.
REFERENCE   4  (bases 1 to 2745)
  AUTHORS   Cho,J., Horikawa,Y., Oiwa,Y., Hosomichi,K., Yabe,D. and Imai,T.
  TITLE     Glucokinase Variant Proteins Are Resistant to Fasting-Induced
            Uridine Diphosphate Glucose-Dependent Degradation in Maturity-Onset
            Diabetes of the Young Type 2 Patients
  JOURNAL   Int J Mol Sci 24 (21), 15842 (2023)
   PUBMED   37958824
  REMARK    GeneRIF: Glucokinase Variant Proteins Are Resistant to
            Fasting-Induced Uridine Diphosphate Glucose-Dependent Degradation
            in Maturity-Onset Diabetes of the Young Type 2 Patients.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2745)
  AUTHORS   Naylor,R., Knight Johnson,A. and del Gaudio,D.
  TITLE     Maturity-Onset Diabetes of the Young Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   29792621
REFERENCE   6  (bases 1 to 2745)
  AUTHORS   De Leon,D.D. and Pinney,S.E.
  TITLE     Permanent Neonatal Diabetes Mellitus
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301620
REFERENCE   7  (bases 1 to 2745)
  AUTHORS   Gillis,D.
  TITLE     Nonsyndromic Genetic Hyperinsulinism Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301549
REFERENCE   8  (bases 1 to 2745)
  AUTHORS   Stoffel,M., Patel,P., Lo,Y.M., Hattersley,A.T., Lucassen,A.M.,
            Page,R., Bell,J.I., Bell,G.I., Turner,R.C. and Wainscoat,J.S.
  TITLE     Missense glucokinase mutation in maturity-onset diabetes of the
            young and mutation screening in late-onset diabetes
  JOURNAL   Nat Genet 2 (2), 153-156 (1992)
   PUBMED   1303265
REFERENCE   9  (bases 1 to 2745)
  AUTHORS   Tanizawa,Y., Matsutani,A., Chiu,K.C. and Permutt,M.A.
  TITLE     Human glucokinase gene: isolation, structural characterization, and
            identification of a microsatellite repeat polymorphism
  JOURNAL   Mol Endocrinol 6 (7), 1070-1081 (1992)
   PUBMED   1354840
REFERENCE   10 (bases 1 to 2745)
  AUTHORS   Hattersley,A.T., Turner,R.C., Permutt,M.A., Patel,P., Tanizawa,Y.,
            Chiu,K.C., O'Rahilly,S., Watkins,P.J. and Wainscoat,J.S.
  TITLE     Linkage of type 2 diabetes to the glucokinase gene
  JOURNAL   Lancet 339 (8805), 1307-1310 (1992)
   PUBMED   1349989
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC006454.4 and BC001890.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000162.4.
            
            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].
            
            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.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC001890.1, M88011.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1968189 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000403799.8/ ENSP00000384247.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-16                AC006454.4         63161-63176
            17-2745             BC001890.1         1-2729
FEATURES             Location/Qualifiers
     source          1..2745
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7p13"
     gene            1..2745
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /note="glucokinase"
                     /db_xref="GeneID:2645"
                     /db_xref="HGNC:HGNC:4195"
                     /db_xref="MIM:138079"
     exon            1..531
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     CDS             487..1884
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /EC_number="2.7.1.1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     hexokinase D, pancreatic isozyme; ATP:D-hexose
                     6-phosphotransferase; HK IV; hexokinase type IV;
                     glucokinase (hexokinase 4)"
                     /codon_start=1
                     /product="hexokinase-4 isoform 1"
                     /protein_id="NP_000153.1"
                     /db_xref="CCDS:CCDS5479.1"
                     /db_xref="GeneID:2645"
                     /db_xref="HGNC:HGNC:4195"
                     /db_xref="MIM:138079"
                     /translation="MLDDRARMEAAKKEKVEQILAEFQLQEEDLKKVMRRMQKEMDRG
                     LRLETHEEASVKMLPTYVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGEGEEGQWSVK
                     TKHQMYSIPEDAMTGTAEMLFDYISECISDFLDKHQMKHKKLPLGFTFSFPVRHEDID
                     KGILLNWTKGFKASGAEGNNVVGLLRDAIKRRGDFEMDVVAMVNDTVATMISCYYEDH
                     QCEVGMIVGTGCNACYMEEMQNVELVEGDEGRMCVNTEWGAFGDSGELDEFLLEYDRL
                     VDESSANPGQQLYEKLIGGKYMGELVRLVLLRLVDENLLFHGEASEQLRTRGAFETRF
                     VSQVESDTGDRKQIYNILSTLGLRPSTTDCDIVRRACESVSTRAAHMCSAGLAGVINR
                     MRESRSEDVMRITVGVDGSVYKLHPSFKERFHASVRRLTPSCEITFIESEEGSGRGAA
                     LVSAVACKKACMLGQ"
     exon            532..694
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            695..849
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            850..969
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            970..1065
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1066..1165
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1166..1349
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1350..1505
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1506..1739
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1740..2745
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2722..2727
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /note="hexamer: ATTAAA"
     polyA_site      2745
                     /gene="GCK"
                     /gene_synonym="FGQTL3; GK; GLK; HHF3; HK4; HKIV; HXKP;
                     LGLK; MODY2; PNDM1"
                     /note="major polyA site"
ORIGIN      
        1 actccacacc tggctggagc aggaaatgcc gagcggcgcc tgagccccag ggaagcaggc
       61 taggatgtga gagacacagt cacctgcagc ctaattactc aaaagctgtc cccaggtcac
      121 agaagggaga ggacatttcc cactgaatct gtctgaagga cactaagccc cacagctcaa
      181 cacaaccagg agagaaagcg ctgaggacgc cacccaagcg cccagcaatg gccctgcctg
      241 gagaacatcc aggctcagtg aggaagggtc cagaagggaa tgcttgccga ctcgttggag
      301 aacaatgaaa aggaggaaac tgtgactgaa cctcaaaccc caaaccagcc cgaggagaac
      361 cacattctcc cagggaccca gggcgggccg tgacccctgc ggcggagaag ccttggatat
      421 ttccacttca gaagcctact ggggaaggct gaggggtccc agctccccac gctggctgct
      481 gtgcagatgc tggacgacag agccaggatg gaggccgcca agaaggagaa ggtagagcag
      541 atcctggcag agttccagct gcaggaggag gacctgaaga aggtgatgag acggatgcag
      601 aaggagatgg accgcggcct gaggctggag acccatgaag aggccagtgt gaagatgctg
      661 cccacctacg tgcgctccac cccagaaggc tcagaagtcg gggacttcct ctccctggac
      721 ctgggtggca ctaacttcag ggtgatgctg gtgaaggtgg gagaaggtga ggaggggcag
      781 tggagcgtga agaccaaaca ccagatgtac tccatccccg aggacgccat gaccggcact
      841 gctgagatgc tcttcgacta catctctgag tgcatctccg acttcctgga caagcatcag
      901 atgaaacaca agaagctgcc cctgggcttc accttctcct ttcctgtgag gcacgaagac
      961 atcgataagg gcatccttct caactggacc aagggcttca aggcctcagg agcagaaggg
     1021 aacaatgtcg tggggcttct gcgagacgct atcaaacgga gaggggactt tgaaatggat
     1081 gtggtggcaa tggtgaatga cacggtggcc acgatgatct cctgctacta cgaagaccat
     1141 cagtgcgagg tcggcatgat cgtgggcacg ggctgcaatg cctgctacat ggaggagatg
     1201 cagaatgtgg agctggtgga gggggacgag ggccgcatgt gcgtcaatac cgagtggggc
     1261 gccttcgggg actccggcga gctggacgag ttcctgctgg agtatgaccg cctggtggac
     1321 gagagctctg caaaccccgg tcagcagctg tatgagaagc tcataggtgg caagtacatg
     1381 ggcgagctgg tgcggcttgt gctgctcagg ctcgtggacg aaaacctgct cttccacggg
     1441 gaggcctccg agcagctgcg cacacgcgga gccttcgaga cgcgcttcgt gtcgcaggtg
     1501 gagagcgaca cgggcgaccg caagcagatc tacaacatcc tgagcacgct ggggctgcga
     1561 ccctcgacca ccgactgcga catcgtgcgc cgcgcctgcg agagcgtgtc tacgcgcgct
     1621 gcgcacatgt gctcggcggg gctggcgggc gtcatcaacc gcatgcgcga gagccgcagc
     1681 gaggacgtaa tgcgcatcac tgtgggcgtg gatggctccg tgtacaagct gcaccccagc
     1741 ttcaaggagc ggttccatgc cagcgtgcgc aggctgacgc ccagctgcga gatcaccttc
     1801 atcgagtcgg aggagggcag tggccggggc gcggccctgg tctcggcggt ggcctgtaag
     1861 aaggcctgta tgctgggcca gtgagagcag tggccgcaag cgcagggagg atgccacagc
     1921 cccacagcac ccaggctcca tggggaagtg ctccccacac gtgctcgcag cctggcgggg
     1981 caggaggcct ggccttgtca ggacccaggc cgcctgccat accgctgggg aacagagcgg
     2041 gcctcttccc tcagtttttc ggtgggacag ccccagggcc ctaacggggg tgcggcagga
     2101 gcaggaacag agactctgga agccccccac ctttctcgct ggaatcaatt tcccagaagg
     2161 gagttgctca ctcaggactt tgatgcattt ccacactgtc agagctgttg gcctcgcctg
     2221 ggcccaggct ctgggaaggg gtgccctctg gatcctgctg tggcctcact tccctgggaa
     2281 ctcatcctgt gtggggaggc agctccaaca gcttgaccag acctagacct gggccaaaag
     2341 ggcagccagg ggctgctcat cacccagtcc tggccatttt cttgcctgag gctcaagagg
     2401 cccagggagc aatgggaggg ggctccatgg aggaggtgtc ccaagctttg aataccccca
     2461 gagacctttt ctctcccata ccatcactga gtggcttgtg attctgggat ggaccctcgc
     2521 agcaggtgca agagacagag cccccaagcc tctgccccaa ggggcccaca aaggggagaa
     2581 gggccagccc tacatcttca gctcccatag cgctggctca ggaagaaacc ccaagcagca
     2641 ttcagcacac cccaagggac aaccccatca tatgacatgc caccctctcc atgcccaacc
     2701 taagattgtg tgggtttttt aattaaaaat gttaaaagtt ttaaa
//
