LOCUS       NM_018283               1938 bp    mRNA    linear   PRI 09-JUL-2024
DEFINITION  Homo sapiens nudix hydrolase 15 (NUDT15), transcript variant 1,
            mRNA.
ACCESSION   NM_018283
VERSION     NM_018283.4
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 1938)
  AUTHORS   Sabirova,Z., Mahnoor,S., Lasfar,D., Gagne,V., Theoret,Y.,
            Leclerc,J.M., Laverdiere,C., Sinnett,D., Tran,T.H. and
            Krajinovic,M.
  TITLE     Novel variant in Nudix hydrolase 15 gene influences
            6-mercaptopurine toxicity in childhood acute lymphoblastic leukemia
            patients
  JOURNAL   Pharmacogenet Genomics 34 (5), 170-173 (2024)
   PUBMED   38682355
  REMARK    GeneRIF: Novel variant in Nudix hydrolase 15 gene influences
            6-mercaptopurine toxicity in childhood acute lymphoblastic leukemia
            patients.
REFERENCE   2  (bases 1 to 1938)
  AUTHORS   Rosdiana,D.S., Saputri,D.S., Louisa,M. and Setiabudy,R.
  TITLE     NUDT15 Polymorphism and Its Association With Mercaptopurine
            Hematotoxicity in Acute Lymphoblastic Leukemia in Indonesian
            Children
  JOURNAL   In Vivo 38 (4), 2041-2048 (2024)
   PUBMED   38936894
  REMARK    GeneRIF: NUDT15 Polymorphism and Its Association With
            Mercaptopurine Hematotoxicity in Acute Lymphoblastic Leukemia in
            Indonesian Children.
REFERENCE   3  (bases 1 to 1938)
  AUTHORS   Du,S., Huang,X., He,X., Mao,M., Chen,M., Zhang,R., Shao,H., Lv,Z.,
            Liu,X. and Chuan,J.
  TITLE     Association of NUDT15 gene polymorphism with adverse reaction,
            treatment efficacy, and dose of 6-mercaptopurine in patients with
            acute lymphoblastic leukemia: a systematic review and meta-analysis
  JOURNAL   Haematologica 109 (4), 1053-1068 (2024)
   PUBMED   37794799
  REMARK    GeneRIF: Association of NUDT15 gene polymorphism with adverse
            reaction, treatment efficacy, and dose of 6-mercaptopurine in
            patients with acute lymphoblastic leukemia: a systematic review and
            meta-analysis.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 1938)
  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   5  (bases 1 to 1938)
  AUTHORS   Moriyama,T., Nishii,R., Perez-Andreu,V., Yang,W., Klussmann,F.A.,
            Zhao,X., Lin,T.N., Hoshitsuki,K., Nersting,J., Kihira,K.,
            Hofmann,U., Komada,Y., Kato,M., McCorkle,R., Li,L., Koh,K.,
            Najera,C.R., Kham,S.K., Isobe,T., Chen,Z., Chiew,E.K., Bhojwani,D.,
            Jeffries,C., Lu,Y., Schwab,M., Inaba,H., Pui,C.H., Relling,M.V.,
            Manabe,A., Hori,H., Schmiegelow,K., Yeoh,A.E., Evans,W.E. and
            Yang,J.J.
  TITLE     NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic
            toxicity
  JOURNAL   Nat Genet 48 (4), 367-373 (2016)
   PUBMED   26878724
  REMARK    GeneRIF: Patients with defective NUDT15 alleles showed excessive
            levels of thiopurine active metabolites and toxicity.
            [meta-analysis]
REFERENCE   6  (bases 1 to 1938)
  AUTHORS   Yang,S.K., Hong,M., Baek,J., Choi,H., Zhao,W., Jung,Y.,
            Haritunians,T., Ye,B.D., Kim,K.J., Park,S.H., Park,S.K., Yang,D.H.,
            Dubinsky,M., Lee,I., McGovern,D.P., Liu,J. and Song,K.
  TITLE     A common missense variant in NUDT15 confers susceptibility to
            thiopurine-induced leukopenia
  JOURNAL   Nat Genet 46 (9), 1017-1020 (2014)
   PUBMED   25108385
  REMARK    GeneRIF: Authros identified a nonsynonymous SNP in NUDT15 (encoding
            p.Arg139Cys) that was strongly associated with thiopurine-induced
            early leukopenia (odds ratio (OR) = 35.6; P(combined) = 4.88 x
            10(-94)).
REFERENCE   7  (bases 1 to 1938)
  AUTHORS   Takagi,Y., Setoyama,D., Ito,R., Kamiya,H., Yamagata,Y. and
            Sekiguchi,M.
  TITLE     Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine
            and deoxyguanosine diphosphates: comparison with MTH1 and MTH2
  JOURNAL   J Biol Chem 287 (25), 21541-21549 (2012)
   PUBMED   22556419
REFERENCE   8  (bases 1 to 1938)
  AUTHORS   Hori,M., Satou,K., Harashima,H. and Kamiya,H.
  TITLE     Suppression of mutagenesis by 8-hydroxy-2'-deoxyguanosine
            5'-triphosphate (7,8-dihydro-8-oxo-2'-deoxyguanosine
            5'-triphosphate) by human MTH1, MTH2, and NUDT5
  JOURNAL   Free Radic Biol Med 48 (9), 1197-1201 (2010)
   PUBMED   20144704
  REMARK    GeneRIF: human MTH1, MTH2, and NUDT5 proteins act as a defense
            against the mutagenesis induced by oxidized dGTP.
REFERENCE   9  (bases 1 to 1938)
  AUTHORS   Yu,Y., Cai,J.P., Tu,B., Wu,L., Zhao,Y., Liu,X., Li,L., McNutt,M.A.,
            Feng,J., He,Q., Yang,Y., Wang,H., Sekiguchi,M. and Zhu,W.G.
  TITLE     Proliferating cell nuclear antigen is protected from degradation by
            forming a complex with MutT Homolog2
  JOURNAL   J Biol Chem 284 (29), 19310-19320 (2009)
   PUBMED   19419956
  REMARK    GeneRIF: Data demonstrate for the first time that PCNA is protected
            by this newly identified partner molecule MTH2, which is related to
            DNA synthesis and cell cycle progression.
REFERENCE   10 (bases 1 to 1938)
  AUTHORS   Cai,J.P., Ishibashi,T., Takagi,Y., Hayakawa,H. and Sekiguchi,M.
  TITLE     Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine
            nucleotides
  JOURNAL   Biochem Biophys Res Commun 305 (4), 1073-1077 (2003)
   PUBMED   12767940
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK001818.1 and BC064607.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_018283.3.
            
            Summary: This gene encodes an enzyme that belongs to the Nudix
            hydrolase superfamily. Members of this superfamily catalyze the
            hydrolysis of nucleoside diphosphates, including substrates like
            8-oxo-dGTP, which are a result of oxidative damage, and can induce
            base mispairing during DNA replication, causing transversions. The
            encoded enzyme is a negative regulator of thiopurine activation and
            toxicity. Mutations in this gene result in poor metabolism of
            thiopurines, and are associated with thiopurine-induced early
            leukopenia. Multiple pseudogenes of this gene have been identified.
            [provided by RefSeq, Apr 2016].
            
            Transcript Variant: This variant (1) 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 :: BC064607.1, SRR5189661.70458.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000258662.3/ ENSP00000258662.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1288              AK001818.1         160-1447
            1289-1938           BC064607.1         1267-1916
FEATURES             Location/Qualifiers
     source          1..1938
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="13"
                     /map="13q14.2"
     gene            1..1938
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /note="nudix hydrolase 15"
                     /db_xref="GeneID:55270"
                     /db_xref="HGNC:HGNC:23063"
                     /db_xref="MIM:615792"
     exon            1..179
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /inference="alignment:Splign:2.1.0"
     CDS             22..516
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /EC_number="3.6.1.9"
                     /note="isoform 1 is encoded by transcript variant 1;
                     probable 7,8-dihydro-8-oxoguanine triphosphatase NUDT15;
                     nucleoside diphosphate-linked to another moiety X
                     hydrolase 15; nucleotide triphosphate diphosphatase
                     NUDT15; mutT homolog 2; 8-oxo-dGTPase NUDT15; probable
                     8-oxo-dGTP diphosphatase NUDT15; nudix (nucleoside
                     diphosphate linked moiety X)-type motif 15"
                     /codon_start=1
                     /product="nucleotide triphosphate diphosphatase NUDT15
                     isoform 1"
                     /protein_id="NP_060753.1"
                     /db_xref="CCDS:CCDS9407.1"
                     /db_xref="GeneID:55270"
                     /db_xref="HGNC:HGNC:23063"
                     /db_xref="MIM:615792"
                     /translation="MTASAQPRGRRPGVGVGVVVTSCKHPRCVLLGKRKGSVGAGSFQ
                     LPGGHLEFGETWEECAQRETWEEAALHLKNVHFASVVNSFIEKENYHYVTILMKGEVD
                     VTHDSEPKNVEPEKNESWEWVPWEELPPLDQLFWGLRCLKEQGYDPFKEDLNHLVGYK
                     GNHL"
     exon            180..376
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /inference="alignment:Splign:2.1.0"
     exon            377..1938
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1844..1849
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /note="hexamer: AATAAA"
     polyA_site      1868
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /note="major polyA site"
     regulatory      1918..1923
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /note="hexamer: AATAAA"
     polyA_site      1925
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /note="major polyA site"
     polyA_site      1938
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /note="major polyA site"
ORIGIN      
        1 aggcgcgtcc tcccgcgcgc tatgacggcc agcgcacagc cgcgcgggcg gcggccagga
       61 gtcggagtcg gagtcgtggt gaccagctgc aagcatccgc gttgcgtcct cctggggaag
      121 aggaaaggct cggttggagc tggcagtttc caactccctg gaggtcatct ggagttcggt
      181 gaaacctggg aagaatgtgc tcaaagggaa acctgggaag aagcagctct tcacctgaaa
      241 aatgttcact ttgcctcagt tgtgaattct ttcattgaga aggagaatta ccattatgtt
      301 actatattaa tgaaaggaga agtggatgtg actcatgatt cagaaccaaa gaatgtagag
      361 cctgaaaaaa atgaaagttg ggagtgggtt ccttgggaag aactacctcc cctggaccag
      421 cttttctggg gactgcgttg tttaaaagaa caaggctatg atccatttaa agaagatctg
      481 aaccatctgg tgggatacaa aggaaatcat ctctaggtgg ccgagaagat ttgattttct
      541 ttaaaaagac aagaataagg tctggttagg gaatgaaaaa tgtatacatt tcggaacaac
      601 tccattttat ctaaaaaagt tcttgtgatt gccagtttat ttgcagtctc ttaatgtatc
      661 ccccactctt tcagccagta cttgagaaaa tttttctgaa atatgtcatt gaattgtatt
      721 ccagacacag aatacatgat aaatactgat attatgggta atctgctttc catatttacc
      781 tatgatattt actgtgcagt ttgtcattac tagcttgcat ggagtaggat gcagtcaaat
      841 ttgccttagt gtttctgttc aaatagagac ctgaattcaa atattgtagt ttaggttcaa
      901 acagagtatg gctgttgcaa aatttaccaa atttgttgat tacctctttt attaaagaaa
      961 tgttggggag agggtaatat attgtgacaa tttttgcaac ttacagggaa taggacaggt
     1021 cattagggtg tatttcccag gtttccaatt gagaatctaa accaagagaa gtgagacaaa
     1081 ccatctaata tctgtatcat gctattaata ggctgtgatg ttgagtttct cacttactct
     1141 ttctgaggtc cagggtcctt atatgaagag attcatatat atgaagagat tcgtctagag
     1201 cagtggttgt caaagtgtgg tctggggggg cctcaagagc ctttcaaggg tattctaggt
     1261 caaagctgtt tttataacac taagacatca tttcactatt tatagctttt cctttttttt
     1321 atttgagaag gagtcttgct ctgttgccca cattggagtg cagtggcacg atctcagctc
     1381 attgcagcct ccgccacctg ggttcaagca attctcctac ctcagcttcc cgagtagctg
     1441 ggattatagg cacccaccac cacacctggc taatttttgt atttttagtg gagacggggt
     1501 ttcaccatgt tggccaggct ggtctggaac tcctgagctc aagtgatctg cccatctcag
     1561 cctcccaaag tgctgggatt acaggtatga gccacaacgc ccagccatca tttatctttt
     1621 tcactcattt tttcatgagt atgcagagga gttttcaaga ggctatctgg tgtgatattg
     1681 taataggctg aatgcaaaag cagatacaag attccagctt tcgtctgtca tcagacattg
     1741 aagagatttg gagaaatgta aagcagcagt actcttctca ctaatttttg ttgtggttag
     1801 ttagaaaaat ggttattttt agtgggtttt aatatgtgaa aaaaataaaa ttagctattt
     1861 gccaaaaatg tttttatgtg tttatatata cttggttctt gttacttgca aatgattaat
     1921 aaaaatttta agaaattt
//
