LOCUS       NM_000367               3184 bp    mRNA    linear   PRI 09-JUN-2024
DEFINITION  Homo sapiens thiopurine S-methyltransferase (TPMT), transcript
            variant 1, mRNA.
ACCESSION   NM_000367
VERSION     NM_000367.5
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 3184)
  AUTHORS   Fukumoto,Y., Kyono,R., Shibukawa,Y., Tanaka,Y.K., Suzuki,N. and
            Ogra,Y.
  TITLE     Differential molecular mechanisms of substrate recognition by
            selenium methyltransferases, INMT and TPMT, in selenium
            detoxification and excretion
  JOURNAL   J Biol Chem 300 (2), 105599 (2024)
   PUBMED   38159853
  REMARK    GeneRIF: Differential molecular mechanisms of substrate recognition
            by selenium methyltransferases, INMT and TPMT, in selenium
            detoxification and excretion.
REFERENCE   2  (bases 1 to 3184)
  AUTHORS   Smid,A., Stajdohar,M., Milek,M., Urbancic,D., Karas Kuzelicki,N.,
            Tamm,R., Metspalu,A. and Mlinaric-Rascan,I.
  TITLE     Transcriptome analysis reveals involvement of thiopurine
            S-methyltransferase in oxidation-reduction processes
  JOURNAL   Eur J Pharm Sci 192, 106616 (2024)
   PUBMED   37865284
  REMARK    GeneRIF: Transcriptome analysis reveals involvement of thiopurine
            S-methyltransferase in oxidation-reduction processes.
REFERENCE   3  (bases 1 to 3184)
  AUTHORS   von Muhlenbrock,C., Estay,C., Covarrubias,N., Miranda,J. and
            Venegas,M.
  TITLE     The c.415C>T polymorphism in NUDT15 is more frequent than the
            polymorphisms in TPMT in Chilean patients who use thiopurine drugs
  JOURNAL   Pharmacogenet Genomics 33 (7), 161-163 (2023)
   PUBMED   37556121
  REMARK    GeneRIF: The c.415C>T polymorphism in NUDT15 is more frequent than
            the polymorphisms in TPMT in Chilean patients who use thiopurine
            drugs.
REFERENCE   4  (bases 1 to 3184)
  AUTHORS   Mora,Y., Villegas,C., Mora,Y.M. and Moreno,N.
  TITLE     TPMT gene polymorphisms (c.238G>C, c.460G>A and c.719A>G) in a
            healthy Venezuelan population
  JOURNAL   Pharmacogenomics 24 (4), 219-225 (2023)
   PUBMED   36946340
  REMARK    GeneRIF: TPMT gene polymorphisms (c.238G>C, c.460G>A and c.719A>G)
            in a healthy Venezuelan population.
REFERENCE   5  (bases 1 to 3184)
  AUTHORS   Okada,Y., Nakamura,K., Wada,M., Nakamura,T., Tsukamoto,N.,
            Nojima,Y., Horiuchi,R. and Yamamoto,K.
  TITLE     Genotyping of thiopurine methyltransferase using pyrosequencing
  JOURNAL   Biol Pharm Bull 28 (4), 677-681 (2005)
   PUBMED   15802809
  REMARK    GeneRIF: Observational study of genetic testing. (HuGE Navigator)
REFERENCE   6  (bases 1 to 3184)
  AUTHORS   Szumlanski,C., Otterness,D., Her,C., Lee,D., Brandriff,B.,
            Kelsell,D., Spurr,N., Lennard,L., Wieben,E. and Weinshilboum,R.
  TITLE     Thiopurine methyltransferase pharmacogenetics: human gene cloning
            and characterization of a common polymorphism
  JOURNAL   DNA Cell Biol 15 (1), 17-30 (1996)
   PUBMED   8561894
REFERENCE   7  (bases 1 to 3184)
  AUTHORS   Lee,D., Szumlanski,C., Houtman,J., Honchel,R., Rojas,K.,
            Overhauser,J., Wieben,E.D. and Weinshilboum,R.M.
  TITLE     Thiopurine methyltransferase pharmacogenetics. Cloning of human
            liver cDNA and a processed pseudogene on human chromosome 18q21.1
  JOURNAL   Drug Metab Dispos 23 (3), 398-405 (1995)
   PUBMED   7628307
REFERENCE   8  (bases 1 to 3184)
  AUTHORS   Krynetski,E.Y., Schuetz,J.D., Galpin,A.J., Pui,C.H., Relling,M.V.
            and Evans,W.E.
  TITLE     A single point mutation leading to loss of catalytic activity in
            human thiopurine S-methyltransferase
  JOURNAL   Proc Natl Acad Sci U S A 92 (4), 949-953 (1995)
   PUBMED   7862671
REFERENCE   9  (bases 1 to 3184)
  AUTHORS   Honchel,R., Aksoy,I.A., Szumlanski,C., Wood,T.C., Otterness,D.M.,
            Wieben,E.D. and Weinshilboum,R.M.
  TITLE     Human thiopurine methyltransferase: molecular cloning and
            expression of T84 colon carcinoma cell cDNA
  JOURNAL   Mol Pharmacol 43 (6), 878-887 (1993)
   PUBMED   8316220
REFERENCE   10 (bases 1 to 3184)
  AUTHORS   Weinshilboum,R.M., Raymond,F.A. and Pazmino,P.A.
  TITLE     Human erythrocyte thiopurine methyltransferase: radiochemical
            microassay and biochemical properties
  JOURNAL   Clin Chim Acta 85 (3), 323-333 (1978)
   PUBMED   657528
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL589723.7.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 20, 2020 this sequence version replaced NM_000367.4.
            
            Summary: This gene encodes the enzyme that metabolizes thiopurine
            drugs via S-adenosyl-L-methionine as the S-methyl donor and
            S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as
            6-mercaptopurine are used as chemotherapeutic agents. Genetic
            polymorphisms that affect this enzymatic activity are correlated
            with variations in sensitivity and toxicity to such drugs within
            individuals, causing thiopurine S-methyltransferase deficiency.
            Related pseudogenes have been identified on chromosomes 3, 18 and
            X. [provided by RefSeq, Aug 2014].
            
            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 :: SRR14038193.1160053.1, S62904.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000309983.5/ ENSP00000312304.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-45                AL589723.7         117588-117632       c
            46-229              AL589723.7         111543-111726       c
            230-322             AL589723.7         110378-110470       c
            323-455             AL589723.7         106151-106283       c
            456-508             AL589723.7         102220-102272       c
            509-583             AL589723.7         101518-101592       c
            584-669             AL589723.7         96359-96444         c
            670-714             AL589723.7         94688-94732         c
            715-3184            AL589723.7         90866-93335         c
FEATURES             Location/Qualifiers
     source          1..3184
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p22.3"
     gene            1..3184
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /note="thiopurine S-methyltransferase"
                     /db_xref="GeneID:7172"
                     /db_xref="HGNC:HGNC:12014"
                     /db_xref="MIM:187680"
     exon            1..45
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     exon            46..229
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     CDS             90..827
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /EC_number="2.1.1.67"
                     /note="isoform 1 is encoded by transcript variant 1;
                     S-adenosyl-L-methionine:thiopurine S-methyltransferase"
                     /codon_start=1
                     /product="thiopurine S-methyltransferase isoform 1"
                     /protein_id="NP_000358.1"
                     /db_xref="CCDS:CCDS4543.1"
                     /db_xref="GeneID:7172"
                     /db_xref="HGNC:HGNC:12014"
                     /db_xref="MIM:187680"
                     /translation="MDGTRTSLDIEEYSDTEVQKNQVLTLEEWQDKWVNGKTAFHQEQ
                     GHQLLKKHLDTFLKGKSGLRVFFPLCGKAVEMKWFADRGHSVVGVEISELGIQEFFTE
                     QNLSYSEEPITEIPGTKVFKSSSGNISLYCCSIFDLPRTNIGKFDMIWDRGALVAINP
                     GDRKCYADTMFSLLGKKFQYLLCVLSYDPTKHPGPPFYVPHAEIERLFGKICNIRCLE
                     KVDAFEERHKSWGIDCLFEKLYLLTEK"
     exon            230..322
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     exon            323..455
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     exon            456..508
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     exon            509..583
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     exon            584..669
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     exon            670..714
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     exon            715..3184
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1760..1765
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /note="hexamer: AATAAA"
     polyA_site      1787
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /note="major polyA site"
     regulatory      3156..3161
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /note="hexamer: ATTAAA"
     polyA_site      3184
                     /gene="TPMT"
                     /gene_synonym="TPMTD"
                     /note="major polyA site"
ORIGIN      
        1 gtcattggtg gcggaggcaa tggccggcaa ccagctgtaa gcgaggcacg gaagacatat
       61 gcttgtgaga caaaggtgtc tctgaaacta tggatggtac aagaacttca cttgacattg
      121 aagagtactc ggatactgag gtacagaaaa accaagtact aactctggaa gaatggcaag
      181 acaagtgggt gaacggcaag actgcttttc atcaggaaca aggacatcag ctattaaaga
      241 agcatttaga tactttcctt aaaggcaaga gtggactgag ggtatttttt cctctttgcg
      301 gaaaagcggt tgagatgaaa tggtttgcag accggggaca cagtgtagtt ggtgtggaaa
      361 tcagtgaact tgggatacaa gaatttttta cagagcagaa tctttcttac tcagaagaac
      421 caatcaccga aattcctgga accaaagtat ttaagagttc ttcggggaac atttcattgt
      481 actgttgcag tatttttgat cttcccagga caaatattgg caaatttgac atgatttggg
      541 atagaggagc attagttgcc atcaatccag gtgatcgcaa atgctatgca gatacaatgt
      601 tttccctcct gggaaagaag tttcagtatc tcctgtgtgt tctttcttat gatccaacta
      661 aacatccagg tccaccattt tatgttccac atgctgaaat tgaaaggttg tttggtaaaa
      721 tatgcaatat acgttgtctt gagaaggttg atgcttttga agaacgacat aaaagttggg
      781 gaattgactg tctttttgaa aagttatatc tacttacaga aaagtaaatg agacatagat
      841 aaaataaaat cacactgaca tgtttttgag gaattgaaaa ttatgctaaa gcctgaaaat
      901 gtaatggatg aatttttaaa attgtttata aatcatatga tagatcttta ctaaaaatgg
      961 ctttttagta aagccattta ctttttctaa aaaagtttta gaagaaaaag atgtaactaa
     1021 acttttaaag tagctccttt ggagaggaga ttatgatgtg aaagattatg cctatgtgtc
     1081 ttgcagattg caagatattt taccaatcag catgtgttac ctgtacaatt aaaaaaatat
     1141 ttcaaaatgc aatgcatatt aaatataata cacacagaaa aactggcatt tattttgttt
     1201 tatttttttg agatggagtt tcgttcttgt tgcccaacct ggagtgcaat ggtgcaatct
     1261 cagctcactg caacctctgc ctcccaggtt caggtgattc tcctgcctca gcctcctgag
     1321 tagctgggat tacaggtgtg cgccaccacg cccagctaat tttttgtatt tttagtagag
     1381 acagggtttc accatgttgg tcaggctgat ctcgagctcc tgacctcagg tgatctaccc
     1441 acctcggcct cccaaagtgc tgggattaca ggcgtgagcc actgcacctg gcctgacatt
     1501 ctttatgaaa tttagaattg ttgaagaact ataacatttc agtagggttc aaggtggtcc
     1561 caaaagttat ataaaagatt agtttttact ataaaccctt gtcttttact cagatcctag
     1621 catccctttt cacatggttt ctccatgtat ataacagaat caagaaacaa attttaatta
     1681 aacaatctgt aacagaatca agaaacaaat acattttaat taaacaatct atatggaaca
     1741 aacattccca aattctaaga ataaattttt ctttaagttt tctctgagtt tggcaattgt
     1801 tgttttttat aatttaatct gtttaaatca tcaggtctta taaaatataa tgtacttaga
     1861 gctggattca tggctgttta ttatgaaagg ttagatttct cagttcttct ttaaccacat
     1921 tttgttatat cagacagtcc tctataactc tgtactaccc aacaactaaa tggtttagat
     1981 tgtttagctc atgttaatag gatggttgtg tattataaaa aacgagttac gtgtgtgtgt
     2041 gcacgcatgc acgcacatgt gctggcttaa aggttgttaa tgcaaggttt ggggtcccct
     2101 ttaacactgg tgaaagctac ggtactctcc ccagagatat gtcttgtcag cctctctagt
     2161 tccccttggc ctgcatgtac aaacttctac cctagaagct ctctgccatc gatgtattct
     2221 aatagatttg taaggctatt aatttgaagc aactccttgc tcacagtgat tcttgcttct
     2281 ctgagacctg ctcccagtcg atactgtggg cttcagaagc catgactccc caactctgcc
     2341 tgtatcaccg gttgaatgga caactaaccc gagctggacc aacacaattc tctccagaga
     2401 cttttgattt tacttttatg tagagacagg gtctcacttt gttgcccacg ctgatgttga
     2461 acttgacgtg aggcctcaag cagtcctcct gtcttggcca cccaaagtgc taggattaca
     2521 ggtatgagcc attgcgctgg ccctcttcat aggcttttgg acttgggaat agaaaagcaa
     2581 ccccgtctct actaaaaata caaaaaaatt agccaggcgt ggtggcacgt gcctgtaatc
     2641 ccagctactt gggaggctga ggcaggagaa tcacttgaac ctaggaggcg gaggttgcag
     2701 tgagctgaga tcatgccact gcacgcaagc ctgggcaaca gagcaagact ctgtctcaaa
     2761 agaaagaaaa agaaaagaaa aaaaagaaag gcaagttgac tgctgaaagg ggaatctgtg
     2821 tacgcctggg agctgtgggg cagccacatt ccagcacatg gatctgagaa acagaacgct
     2881 gatctgcaga aagagatgag aaccaaagag aggccacctg cgtcctgggt ccattttcat
     2941 cctccctgaa gcccagctgc ccagggtggg gagaaacacc ctgtgtccat gggatagagt
     3001 cctttccgct tgcagttgtg cccaaagaat cttaaataca aatgagatat ccttaggtag
     3061 ttgatcattt atgtaatatg tgtcttcact ggggaatact gacttcctaa aatctcaaga
     3121 tggaagatat accacatgta aattatttta gagcaattaa attgttttca ggattttcca
     3181 aaaa
//
