LOCUS       NM_024006                840 bp    mRNA    linear   PRI 27-MAY-2024
DEFINITION  Homo sapiens vitamin K epoxide reductase complex subunit 1
            (VKORC1), transcript variant 1, mRNA.
ACCESSION   NM_024006 XM_290707
VERSION     NM_024006.6
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 840)
  AUTHORS   Drent,M., Wijnen,P., Bekers,O. and Bast,A.
  TITLE     Is a Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1)
            Polymorphism a Risk Factor for Nephrolithiasis in Sarcoidosis?
  JOURNAL   Int J Mol Sci 25 (8), 4448 (2024)
   PUBMED   38674033
  REMARK    GeneRIF: Is a Vitamin K Epoxide Reductase Complex Subunit 1
            (VKORC1) Polymorphism a Risk Factor for Nephrolithiasis in
            Sarcoidosis?
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 840)
  AUTHORS   Rodriguez-Fernandez,K., Reynaldo-Fernandez,G., Reyes-Gonzalez,S.,
            de Las Barreras,C., Rodriguez-Vera,L., Vlaar,C., Monbaliu,J.M.,
            Stelzer,T., Duconge,J. and Mangas-Sanjuan,V.
  TITLE     New insights into the role of VKORC1 polymorphisms for optimal
            warfarin dose selection in Caribbean Hispanic patients through an
            external validation of a population PK/PD model
  JOURNAL   Biomed Pharmacother 170, 115977 (2024)
   PUBMED   38056237
  REMARK    GeneRIF: New insights into the role of VKORC1 polymorphisms for
            optimal warfarin dose selection in Caribbean Hispanic patients
            through an external validation of a population PK/PD model.
REFERENCE   3  (bases 1 to 840)
  AUTHORS   Ilut,S., Vesa,S.C., Vacaras,V., Sipos-Lascu,D., Barsan,C.,
            Pop,R.M., Crisan,S., Macarie,A.E., Coada,C.A., Perju-Dumbrava,L.,
            Muresanu,D.F. and Buzoianu,A.D.
  TITLE     Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX
            rs11676382 polymorphisms and acute ischemic stroke
  JOURNAL   Medicine (Baltimore) 102 (34), e34836 (2023)
   PUBMED   37653796
  REMARK    GeneRIF: Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX
            rs11676382 polymorphisms and acute ischemic stroke.
REFERENCE   4  (bases 1 to 840)
  AUTHORS   Giraldo-Ocampo,S., Diaz-Ordonez,L., Silva-Cuero,Y.K.,
            Gutierrez-Medina,J.D., Candelo,E., Diaz,J.A. and Pachajoa,H.
  TITLE     Frequency of polymorphisms in the CYP2C9, VKORC1, and CYP4F2 genes
            related to the metabolism of Warfarin in healthy donors from Cali,
            Colombia
  JOURNAL   Medicine (Baltimore) 102 (30), e34204 (2023)
   PUBMED   37505171
  REMARK    GeneRIF: Frequency of polymorphisms in the CYP2C9, VKORC1, and
            CYP4F2 genes related to the metabolism of Warfarin in healthy
            donors from Cali, Colombia.
REFERENCE   5  (bases 1 to 840)
  AUTHORS   Goodstadt,L. and Ponting,C.P.
  TITLE     Vitamin K epoxide reductase: homology, active site and catalytic
            mechanism
  JOURNAL   Trends Biochem Sci 29 (6), 289-292 (2004)
   PUBMED   15276181
REFERENCE   6  (bases 1 to 840)
  AUTHORS   Li,T., Chang,C.Y., Jin,D.Y., Lin,P.J., Khvorova,A. and
            Stafford,D.W.
  TITLE     Identification of the gene for vitamin K epoxide reductase
  JOURNAL   Nature 427 (6974), 541-544 (2004)
   PUBMED   14765195
  REMARK    GeneRIF: identification of the gene for VKOR based on specific
            inhibition of VKOR activity by a single siRNA pool
REFERENCE   7  (bases 1 to 840)
  AUTHORS   Rost,S., Fregin,A., Ivaskevicius,V., Conzelmann,E., Hortnagel,K.,
            Pelz,H.J., Lappegard,K., Seifried,E., Scharrer,I., Tuddenham,E.G.,
            Muller,C.R., Strom,T.M. and Oldenburg,J.
  TITLE     Mutations in VKORC1 cause warfarin resistance and multiple
            coagulation factor deficiency type 2
  JOURNAL   Nature 427 (6974), 537-541 (2004)
   PUBMED   14765194
  REMARK    GeneRIF: using a positional cloning approach that integrated
            mapping information from three species, the gene VKORC1 that is
            mutated in combined deficiency of vitamin-K-dependent clotting
            factors type 2 and warfarin resistance was identified
REFERENCE   8  (bases 1 to 840)
  AUTHORS   Clark,H.F., Gurney,A.L., Abaya,E., Baker,K., Baldwin,D., Brush,J.,
            Chen,J., Chow,B., Chui,C., Crowley,C., Currell,B., Deuel,B.,
            Dowd,P., Eaton,D., Foster,J., Grimaldi,C., Gu,Q., Hass,P.E.,
            Heldens,S., Huang,A., Kim,H.S., Klimowski,L., Jin,Y., Johnson,S.,
            Lee,J., Lewis,L., Liao,D., Mark,M., Robbie,E., Sanchez,C.,
            Schoenfeld,J., Seshagiri,S., Simmons,L., Singh,J., Smith,V.,
            Stinson,J., Vagts,A., Vandlen,R., Watanabe,C., Wieand,D., Woods,K.,
            Xie,M.H., Yansura,D., Yi,S., Yu,G., Yuan,J., Zhang,M., Zhang,Z.,
            Goddard,A., Wood,W.I., Godowski,P. and Gray,A.
  TITLE     The secreted protein discovery initiative (SPDI), a large-scale
            effort to identify novel human secreted and transmembrane proteins:
            a bioinformatics assessment
  JOURNAL   Genome Res 13 (10), 2265-2270 (2003)
   PUBMED   12975309
  REMARK    Erratum:[Genome Res. 2003 Dec;13(12):2759]
REFERENCE   9  (bases 1 to 840)
  AUTHORS   Fregin,A., Rost,S., Wolz,W., Krebsova,A., Muller,C.R. and
            Oldenburg,J.
  TITLE     Homozygosity mapping of a second gene locus for hereditary combined
            deficiency of vitamin K-dependent clotting factors to the
            centromeric region of chromosome 16
  JOURNAL   Blood 100 (9), 3229-3232 (2002)
   PUBMED   12384421
REFERENCE   10 (bases 1 to 840)
  AUTHORS   Oldenburg,J., von Brederlow,B., Fregin,A., Rost,S., Wolz,W.,
            Eberl,W., Eber,S., Lenz,E., Schwaab,R., Brackmann,H.H.,
            Effenberger,W., Harbrecht,U., Schurgers,L.J., Vermeer,C. and
            Muller,C.R.
  TITLE     Congenital deficiency of vitamin K dependent coagulation factors in
            two families presents as a genetic defect of the vitamin
            K-epoxide-reductase-complex
  JOURNAL   Thromb Haemost 84 (6), 937-941 (2000)
   PUBMED   11154138
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI822140.1, BC002911.2,
            AY423044.1 and AY358456.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_024006.5.
            
            Summary: This gene encodes the catalytic subunit of the vitamin K
            epoxide reductase complex, which is responsible for the reduction
            of inactive vitamin K 2,3-epoxide to active vitamin K in the
            endoplasmic reticulum membrane. Vitamin K is a required co-factor
            for carboxylation of glutamic acid residues by vitamin K-dependent
            gamma-carboxylase in blood-clotting enzymes. Allelic variation in
            this gene is associated with vitamin k-dependent clotting factors
            combined deficiency of 2, and increased resistance or sensitivity
            to warfarin, an inhibitor of vitamin K epoxide reductase.
            Pseudogenes of this gene are located on chromosomes 1 and X.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Aug 2015].
            
            Transcript Variant: This variant (1) lacks an alternate in-frame
            exon compared to variant 3. It encodes isoform 1, which is shorter
            than isoform 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 :: AY466113.1, SRR1163655.424216.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000394975.3/ ENSP00000378426.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-30                BI822140.1         159-188
            31-68               BC002911.2         1-38
            69-560              AY423044.1         1-492
            561-602             AY358456.1         366-407
            603-840             BC002911.2         573-810
FEATURES             Location/Qualifiers
     source          1..840
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16p11.2"
     gene            1..840
                     /gene="VKORC1"
                     /gene_synonym="EDTP308; MST134; MST576; VKCFD2; VKOR"
                     /note="vitamin K epoxide reductase complex subunit 1"
                     /db_xref="GeneID:79001"
                     /db_xref="HGNC:HGNC:23663"
                     /db_xref="MIM:608547"
     exon            1..241
                     /gene="VKORC1"
                     /gene_synonym="EDTP308; MST134; MST576; VKCFD2; VKOR"
                     /inference="alignment:Splign:2.1.0"
     CDS             69..560
                     /gene="VKORC1"
                     /gene_synonym="EDTP308; MST134; MST576; VKCFD2; VKOR"
                     /EC_number="1.17.4.4"
                     /note="isoform 1 is encoded by transcript variant 1;
                     vitamin K dependent clotting factors deficiency 2; vitamin
                     K1 epoxide reductase (warfarin-sensitive); phylloquinone
                     epoxide reductase; vitamin K1 2,3-epoxide reductase
                     subunit 1"
                     /codon_start=1
                     /product="vitamin K epoxide reductase complex subunit 1
                     isoform 1"
                     /protein_id="NP_076869.1"
                     /db_xref="CCDS:CCDS10703.1"
                     /db_xref="GeneID:79001"
                     /db_xref="HGNC:HGNC:23663"
                     /db_xref="MIM:608547"
                     /translation="MGSTWGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCD
                     VGTAISCSRVFSSRWGRGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWA
                     SVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKA
                     KRH"
     exon            242..351
                     /gene="VKORC1"
                     /gene_synonym="EDTP308; MST134; MST576; VKCFD2; VKOR"
                     /inference="alignment:Splign:2.1.0"
     exon            352..840
                     /gene="VKORC1"
                     /gene_synonym="EDTP308; MST134; MST576; VKCFD2; VKOR"
                     /inference="alignment:Splign:2.1.0"
     regulatory      818..823
                     /regulatory_class="polyA_signal_sequence"
                     /gene="VKORC1"
                     /gene_synonym="EDTP308; MST134; MST576; VKCFD2; VKOR"
                     /note="hexamer: AATAAA"
     polyA_site      840
                     /gene="VKORC1"
                     /gene_synonym="EDTP308; MST134; MST576; VKCFD2; VKOR"
                     /note="major polyA site"
ORIGIN      
        1 attcgccgcc cggcccctgc tccgtggctg gttttctccg cgggcgcctc gggcggaacc
       61 tggagataat gggcagcacc tgggggagcc ctggctgggt gcggctcgct ctttgcctga
      121 cgggcttagt gctctcgctc tacgcgctgc acgtgaaggc ggcgcgcgcc cgggaccggg
      181 attaccgcgc gctctgcgac gtgggcaccg ccatcagctg ttcgcgcgtc ttctcctcca
      241 ggtggggcag gggtttcggg ctggtggagc atgtgctggg acaggacagc atcctcaatc
      301 aatccaacag catattcggt tgcatcttct acacactaca gctattgtta ggttgcctgc
      361 ggacacgctg ggcctctgtc ctgatgctgc tgagctccct ggtgtctctc gctggttctg
      421 tctacctggc ctggatcctg ttcttcgtgc tctatgattt ctgcattgtt tgtatcacca
      481 cctatgctat caacgtgagc ctgatgtggc tcagtttccg gaaggtccaa gaaccccagg
      541 gcaaggctaa gaggcactga gccctcaacc caagccaggc tgacctcatc tgctttgctt
      601 tggcatgtga gccttgccta agggggcata tctgggtccc tagaaggccc tagatgtggg
      661 gcttctagat taccccctcc tcctgccata cccgcacatg acaatggacc aaatgtgcca
      721 cacgctcgct cttttttaca cccagtgcct ctgactctgt ccccatgggc tggtctccaa
      781 agctctttcc attgcccagg gagggaaggt tctgagcaat aaagtttctt agatcaatca
//
