LOCUS       NM_000110               4423 bp    mRNA    linear   PRI 24-SEP-2024
DEFINITION  Homo sapiens dihydropyrimidine dehydrogenase (DPYD), transcript
            variant 1, mRNA.
ACCESSION   NM_000110
VERSION     NM_000110.4
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 4423)
  AUTHORS   Ikonnikova,A., Fedorinov,D., Gryadunov,D., Heydarov,R., Lyadova,M.,
            Moskalenko,A., Mikhailovich,V., Emelyanova,M. and Lyadov,V.
  TITLE     MIR27A Gene Polymorphism Modifies the Effect of Common DPYD Gene
            Variants on Severe Toxicity in Patients with Gastrointestinal
            Tumors Treated with Fluoropyrimidine-Based Anticancer Therapy
  JOURNAL   Int J Mol Sci 25 (15), 8503 (2024)
   PUBMED   39126072
  REMARK    GeneRIF: MIR27A Gene Polymorphism Modifies the Effect of Common
            DPYD Gene Variants on Severe Toxicity in Patients with
            Gastrointestinal Tumors Treated with Fluoropyrimidine-Based
            Anticancer Therapy.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4423)
  AUTHORS   Chan,T.H., Zhang,J.E. and Pirmohamed,M.
  TITLE     DPYD genetic polymorphisms in non-European patients with severe
            fluoropyrimidine-related toxicity: a systematic review
  JOURNAL   Br J Cancer 131 (3), 498-514 (2024)
   PUBMED   38886557
  REMARK    GeneRIF: DPYD genetic polymorphisms in non-European patients with
            severe fluoropyrimidine-related toxicity: a systematic review.
REFERENCE   3  (bases 1 to 4423)
  AUTHORS   van Kuilenburg,A.B.P., Pleunis-van Empel,M.C.H., Brouwer,R.B.,
            Sijben,A.E.J., Knapen,D.G., Oude Munnink,T.H., van Zanden,J.J.,
            Janssens-Puister,J., Dobritzsch,D., Meinsma,R., Meijer-Jansen,J.,
            van Dooren,S.J.M., Vijzelaar,R., Pop,A., Salomons,G.S., Maring,J.G.
            and Niezen-Koning,K.E.
  TITLE     Lethal Capecitabine Toxicity in Patients With Complete
            Dihydropyrimidine Dehydrogenase Deficiency Due to Ultra-Rare DPYD
            Variants
  JOURNAL   JCO Precis Oncol 8, e2300599 (2024)
   PUBMED   38709992
  REMARK    GeneRIF: Lethal Capecitabine Toxicity in Patients With Complete
            Dihydropyrimidine Dehydrogenase Deficiency Due to Ultra-Rare DPYD
            Variants.
REFERENCE   4  (bases 1 to 4423)
  AUTHORS   Zhang,T., Ambrodji,A., Huang,H., Bouchonville,K.J., Etheridge,A.S.,
            Schmidt,R.E., Bembenek,B.M., Temesgen,Z.B., Wang,Z., Innocenti,F.,
            Stroka,D., Diasio,R.B., Largiader,C.R. and Offer,S.M.
  TITLE     Germline cis variant determines epigenetic regulation of the
            anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase
            (DPYD)
  JOURNAL   Elife 13, 94075 (2024)
   PUBMED   38686795
  REMARK    GeneRIF: Germline cis variant determines epigenetic regulation of
            the anti-cancer drug metabolism gene dihydropyrimidine
            dehydrogenase (DPYD).
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4423)
  AUTHORS   Shestopal,S.A., Johnson,M.R. and Diasio,R.B.
  TITLE     Molecular cloning and characterization of the human
            dihydropyrimidine dehydrogenase promoter
  JOURNAL   Biochim Biophys Acta 1494 (1-2), 162-169 (2000)
   PUBMED   11072080
REFERENCE   6  (bases 1 to 4423)
  AUTHORS   Johnson,M.R., Wang,K., Tillmanns,S., Albin,N. and Diasio,R.B.
  TITLE     Structural organization of the human dihydropyrimidine
            dehydrogenase gene
  JOURNAL   Cancer Res 57 (9), 1660-1663 (1997)
   PUBMED   9135003
REFERENCE   7  (bases 1 to 4423)
  AUTHORS   Lu,Z.H., Zhang,R. and Diasio,R.B.
  TITLE     Purification and characterization of dihydropyrimidine
            dehydrogenase from human liver
  JOURNAL   J Biol Chem 267 (24), 17102-17109 (1992)
   PUBMED   1512248
REFERENCE   8  (bases 1 to 4423)
  AUTHORS   Porter,D.J., Chestnut,W.G., Merrill,B.M. and Spector,T.
  TITLE     Mechanism-based inactivation of dihydropyrimidine dehydrogenase by
            5-ethynyluracil
  JOURNAL   J Biol Chem 267 (8), 5236-5242 (1992)
   PUBMED   1544906
REFERENCE   9  (bases 1 to 4423)
  AUTHORS   Tuchman,M., Roemeling,R.V., Hrushesky,W.A., Sothern,R.B. and
            O'Dea,R.F.
  TITLE     Dihydropyrimidine dehydrogenase activity in human blood mononuclear
            cells
  JOURNAL   Enzyme 42 (1), 15-24 (1989)
   PUBMED   2528450
REFERENCE   10 (bases 1 to 4423)
  AUTHORS   Diasio,R.B., Beavers,T.L. and Carpenter,J.T.
  TITLE     Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical
            basis for familial pyrimidinemia and severe 5-fluorouracil-induced
            toxicity
  JOURNAL   J Clin Invest 81 (1), 47-51 (1988)
   PUBMED   3335642
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA721123.1, U20938.1 and
            AI124948.1.
            
            On Aug 31, 2019 this sequence version replaced NM_000110.3.
            
            Summary: The protein encoded by this gene is a pyrimidine catabolic
            enzyme and the initial and rate-limiting factor in the pathway of
            uracil and thymidine catabolism. Mutations in this gene result in
            dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine
            metabolism associated with thymine-uraciluria and an increased risk
            of toxicity in cancer patients receiving 5-fluorouracil
            chemotherapy. Two transcript variants encoding different isoforms
            have been found for this gene. [provided by RefSeq, May 2009].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: U20938.1, AK291217.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000370192.8/ ENSP00000359211.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-11                DA721123.1         26-36
            12-4420             U20938.1           1-4409
            4421-4423           AI124948.1         4-6                 c
FEATURES             Location/Qualifiers
     source          1..4423
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p21.3"
     gene            1..4423
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /note="dihydropyrimidine dehydrogenase"
                     /db_xref="GeneID:1806"
                     /db_xref="HGNC:HGNC:3012"
                     /db_xref="MIM:612779"
     exon            1..151
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     CDS             113..3190
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /EC_number="1.3.1.2"
                     /note="isoform 1 is encoded by transcript variant 1;
                     dihydrouracil dehydrogenase; dihydrothymine dehydrogenase"
                     /codon_start=1
                     /product="dihydropyrimidine dehydrogenase [NADP(+)]
                     isoform 1"
                     /protein_id="NP_000101.2"
                     /db_xref="CCDS:CCDS30777.1"
                     /db_xref="GeneID:1806"
                     /db_xref="HGNC:HGNC:3012"
                     /db_xref="MIM:612779"
                     /translation="MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRN
                     PDKNCFNCEKLENNFDDIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFIT
                     SIANKNYYGAAKMIFSDNPLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFAT
                     EVFKAMSIPQIRNPSLPPPEKMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFE
                     KQEYVGGLSTSEIPQFRLPYDVVNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGY
                     KAAFIGIGLPEPNKDAIFQGLTQDQGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGV
                     VIVLGAGDTAFDCATSALRCGARRVFIVFRKGFVNIRAVPEEMELAKEEKCEFLPFLS
                     PRKVIVKGGRIVAMQFVRTEQDETGKWNEDEDQMVHLKADVVISAFGSVLSDPKVKEA
                     LSPIKFNRWGLPEVDPETMQTSEAWVFAGGDVVGLANTTVESVNDGKQASWYIHKYVQ
                     SQYGASVSAKPELPLFYTPIDLVDISVEMAGLKFINPFGLASATPATSTSMIRRAFEA
                     GWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMYGPGQSSFLNIELISEKTAAYWCQS
                     VTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDSGADALELNLSCPHGMGERGMGL
                     ACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSIARAAKEGGANGVTATNTVSG
                     LMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTSIARALPGFPILATGGIDS
                     AESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYLKSIEELQDWDGQSPAT
                     VSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQNVAFSPLKRNCFIP
                     KRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCYMTCNDSGYQAIQ
                     FDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLSVNPVC"
     exon            152..262
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            263..345
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            346..433
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            434..595
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            596..792
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            793..874
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            875..962
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            963..1070
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1071..1240
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1241..1451
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1452..1636
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1637..1852
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            1853..2017
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2018..2086
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2087..2170
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2171..2291
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2292..2411
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2412..2554
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2555..2734
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2735..2878
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            2879..3019
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     exon            3020..4423
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4398..4403
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /note="hexamer: AATAAA"
     polyA_site      4423
                     /gene="DPYD"
                     /gene_synonym="DHP; DHPDHASE; DPD; DYPD"
                     /note="major polyA site"
ORIGIN      
        1 agtctgcctg ttttcgactc gcgctccggc tgctgtcact tggctctctg gctggagctt
       61 gaggacgcaa ggagggtttg tcactggcag actcgagact gtaggcactg ccatggcccc
      121 tgtgctcagt aaggactcgg cggacatcga gagtatcctg gctttaaatc ctcgaacaca
      181 aactcatgca actctgtgtt ccacttcggc caagaaatta gacaagaaac attggaaaag
      241 aaatcctgat aagaactgct ttaattgtga gaagctggag aataattttg atgacatcaa
      301 gcacacgact cttggtgagc gaggagctct ccgagaagca atgagatgcc tgaaatgtgc
      361 agatgccccg tgtcagaaga gctgtccaac taatcttgat attaaatcat tcatcacaag
      421 tattgcaaac aagaactatt atggagctgc taagatgata ttttctgaca acccacttgg
      481 tctgacttgt ggaatggtat gtccaacctc tgatctttgt gtaggtggat gcaatttata
      541 tgccactgaa gagggaccca ttaatattgg tggattgcag caatttgcta ctgaggtatt
      601 caaagcaatg agtatcccac agatcagaaa tccttcgctg cctcccccag aaaaaatgtc
      661 tgaagcctat tctgcaaaga ttgctctttt tggtgctggg cctgcaagta taagttgtgc
      721 ttcctttttg gctcgattgg ggtactctga catcactata tttgaaaaac aagaatatgt
      781 tggtggttta agtacttctg aaattcctca gttccggctg ccgtatgatg tagtgaattt
      841 tgagattgag ctaatgaagg accttggtgt aaagataatt tgcggtaaaa gcctttcagt
      901 gaatgaaatg actcttagca ctttgaaaga aaaaggctac aaagctgctt tcattggaat
      961 aggtttgcca gaacccaata aagatgccat cttccaaggc ctgacgcagg accaggggtt
     1021 ttatacatcc aaagactttt tgccacttgt agccaaaggc agtaaagcag gaatgtgcgc
     1081 ctgtcactct ccattgccat cgatacgggg agtcgtgatt gtacttggag ctggagacac
     1141 tgcctttgac tgtgcaacat ctgctctacg ttgtggagct cgccgtgtgt tcatcgtctt
     1201 cagaaaaggc tttgttaata taagagctgt ccctgaggag atggaacttg ctaaggaaga
     1261 aaagtgtgaa tttctgccat tcctgtcccc acggaaggtt atagtaaaag gtgggagaat
     1321 tgttgctatg cagtttgttc ggacagagca agatgaaact ggaaaatgga atgaagatga
     1381 agatcagatg gtccatctga aagccgatgt ggtcatcagt gcctttggtt cagttctgag
     1441 tgatcctaaa gtaaaagaag ccttgagccc tataaaattt aacagatggg gtctcccaga
     1501 agtagatcca gaaactatgc aaactagtga agcatgggta tttgcaggtg gtgatgtcgt
     1561 tggtttggct aacactacag tggaatcggt gaatgatgga aagcaagctt cttggtacat
     1621 tcacaaatac gtacagtcac aatatggagc ttccgtttct gccaagcctg aactacccct
     1681 cttttacact cctattgatc tggtggacat tagtgtagaa atggccggat tgaagtttat
     1741 aaatcctttt ggtcttgcta gcgcaactcc agccaccagc acatcaatga ttcgaagagc
     1801 ttttgaagct ggatggggtt ttgccctcac caaaactttc tctcttgata aggacattgt
     1861 gacaaatgtt tcccccagaa tcatccgggg aaccacctct ggccccatgt atggccctgg
     1921 acaaagctcc tttctgaata ttgagctcat cagtgagaaa acggctgcat attggtgtca
     1981 aagtgtcact gaactaaagg ctgactttcc agacaacatt gtgattgcta gcattatgtg
     2041 cagttacaat aaaaatgact ggacggaact tgccaagaag tctgaggatt ctggagcaga
     2101 tgccctggag ttaaatttat catgtccaca tggcatggga gaaagaggaa tgggcctggc
     2161 ctgtgggcag gatccagagc tggtgcggaa catctgccgc tgggttaggc aagctgttca
     2221 gattcctttt tttgccaagc tgaccccaaa tgtcactgat attgtgagca tcgcaagagc
     2281 tgcaaaggaa ggtggtgcca atggcgttac agccaccaac actgtctcag gtctgatggg
     2341 attaaaatct gatggcacac cttggccagc agtggggatt gcaaagcgaa ctacatatgg
     2401 aggagtgtct gggacagcaa tcagacctat tgctttgaga gctgtgacct ccattgctcg
     2461 tgctctgcct ggatttccca ttttggctac tggtggaatt gactctgctg aaagtggtct
     2521 tcagtttctc catagtggtg cttccgtcct ccaggtatgc agtgccattc agaatcagga
     2581 tttcactgtg atcgaagact actgcactgg cctcaaagcc ctgctttatc tgaaaagcat
     2641 tgaagaacta caagactggg atggacagag tccagctact gtgagtcacc agaaagggaa
     2701 accagttcca cgtatagctg aactcatgga caagaaactg ccaagttttg gaccttatct
     2761 ggaacagcgc aagaaaatca tagcagaaaa caagattaga ctgaaagaac aaaatgtagc
     2821 tttttcacca cttaagagaa actgttttat ccccaaaagg cctattccta ccatcaagga
     2881 tgtaatagga aaagcactgc agtaccttgg aacatttggt gaattgagca acgtagagca
     2941 agttgtggct atgattgatg aagaaatgtg tatcaactgt ggtaaatgct acatgacctg
     3001 taatgattct ggctaccagg ctatacagtt tgatccagaa acccacctgc ccaccataac
     3061 cgacacttgt acaggctgta ctctgtgtct cagtgtttgc cctattgtcg actgcatcaa
     3121 aatggtttcc aggacaacac cttatgaacc aaagagaggc gtacccttat ctgtgaatcc
     3181 ggtgtgttaa ggtgatttgt gaaacagttg ctgtgaactt tcatgtcacc tacatatgct
     3241 gatcttttaa aatcatgatc cttgtgttca gctctttcca aattaaaaca aatatacatt
     3301 ttctaaataa aaatatgtaa tttcaaaata catttgtaag tgtaaaaaat gtctcatgtc
     3361 aatgaccatt caattagtgg tcataaaata gaataattct tttctgagga tagtagttaa
     3421 ataactgtgt ggcagttaat tggatgttca ctgccagttg tcttatgtga aaaattaact
     3481 tttttgtggc aattagtgtg acagtttcca aattgcccta tgctgtgctc catatttgat
     3541 ttctaattgt aagtgaaatt aagcattttg aaacaaagta ctctttaaca tacaagaaaa
     3601 tgtatccaag gaaacatttt atcattaaaa attaccttta attttaatgc tgtttctaag
     3661 aaaatgtagt tagctccata aagtacaaat gaagaaagtc aaaaaattat ttgctatggc
     3721 aggataagaa agcctaaaat tgagtttgta gaactttatt aagtaaaatc cccttcgctg
     3781 aaattgctta tttttggtgt tggatagagg atagggagaa tatttactaa ctaaatacca
     3841 ttcactactc atgcgtgaga tgggtgtaca aactcatcct cttttaatgg catttctctt
     3901 taaactatgt tcctaacaaa atgagatgat aggatagatc ctggttacca ctcttttgct
     3961 gtgcacatac gggctctgac tggttttaat agtcaccttc atgattatag caactaatgt
     4021 ttgaacaaag ctcaaagtat gcaatgcttc attattcaag aatgaaaaat ataatgttga
     4081 taatatatat taagtgtgcc aaatcagttt gactactctc tgttttagtg tttatgttta
     4141 aaagaaatat attttttgtt attattagat aatatttttg tatttctcta ttttcataat
     4201 cagtaaatag tgtcatataa actcatttat ctcctcttca tggcatcttc aatatgaatc
     4261 tataagtagt aaatcagaaa gtaacaatct atggcttatt tctatgacaa attcaagagc
     4321 tagaaaaata aaatgtttca ttatgcactt ttagaaatgc atatttgcca caaaacctgt
     4381 attactgaat aatatcaaat aaaatatcat aaagcatttt aaa
//
