LOCUS       NM_001304745             762 bp    mRNA    linear   PRI 09-JUL-2024
DEFINITION  Homo sapiens nudix hydrolase 15 (NUDT15), transcript variant 2,
            mRNA.
ACCESSION   NM_001304745
VERSION     NM_001304745.2
KEYWORDS    RefSeq.
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 762)
  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 762)
  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 762)
  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 762)
  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 762)
  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 762)
  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 762)
  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 762)
  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 762)
  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 762)
  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 BC050698.1.
            
            On Aug 13, 2020 this sequence version replaced NM_001304745.1.
            
            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 (2) differs in the 3' coding
            region and 3' UTR compared to variant 1. The encoded isoform (2)
            has a distinct, shorter C-terminus than 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 :: BC050698.1, SRR14038191.3580830.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-13                AK001818.1         160-172
            14-762              BC050698.1         1-749
FEATURES             Location/Qualifiers
     source          1..762
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="13"
                     /map="13q14.2"
     gene            1..762
                     /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..459
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /EC_number="3.6.1.9"
                     /note="isoform 2 is encoded by transcript variant 2;
                     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 2"
                     /protein_id="NP_001291674.1"
                     /db_xref="GeneID:55270"
                     /db_xref="HGNC:HGNC:23063"
                     /db_xref="MIM:615792"
                     /translation="MTASAQPRGRRPGVGVGVVVTSCKHPRCVLLGKRKGSVGAGSFQ
                     LPGGHLEFGETWEECAQRETWEEAALHLKNVHFASVVNSFIEKENYHYVTILMKGEVD
                     VTHDSEPKNVEPEKNESKRIIYNHAFFFQESKWSGGILQYVAI"
     exon            180..762
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /inference="alignment:Splign:2.1.0"
     regulatory      741..746
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NUDT15"
                     /gene_synonym="MTH2; NUDT15D"
                     /note="hexamer: AATAAA"
     polyA_site      762
                     /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 atgaaagtaa gagaattata tataatcatg catttttctt tcaggagagc
      421 aagtggtctg gaggaatatt acagtatgtt gccatatgaa gagaatgcta ttgtctgaat
      481 gcttgtgttc ccccaaaatt ctatgtagaa atcctaactc ccatgacgag gttttaggag
      541 gttggggccc ttgggaggtg attagatcat aagataatga atgggattca tgcccttata
      601 aaagagaccc ctgacccctt ccatgatgta aagatacaga gagaagatcg ttgtctgtga
      661 acctggaagt gggccctccc cagatatgga atctgccagt gtcttgatct tggacttccc
      721 agtctctaga actgttgaga aataaatttc tgttgctcat aa
//
