Recombinant Human Nucleotide triphosphate diphosphatase NUDT15 (NUDT15)

1. Results show that 6-TGN levels were substantially low in patients with NUDT15 variants who showed highest hematopoietic toxicity. The low ratio of 6-TGN level to 6-mercaptopurine dose in patients with NUDT15 variants seems to be caused by enhanced incorporation of active thiopurine metabolites into DNA. PMID: 28903549
2. Mutation rate of NUDT15 in Chinese inflammatory bowel disease patients is higher than that of TPMT. NUDT15 polymorphism is a better predictor for AZA-induced leukopenia than TPMT polymorphism. PMID: 29491687
3. Mutations in exon 1 of NUDT15 also affect thiopurine-induced leukopenia in patients with inflammatory bowel disease. PMID: 29398872
4. With increasing copy numbers of the risk T allele at NUDT15. PMID: 29210335
5. results of this meta-analysis confirm that NUDT15 c.415C>T may be an important predictor of thiopurine-induced leukocytopenia in Asians PMID: 28470355
6. NUDT15 c.415C>T, c.36_37insGGAGTC, and c.52G>A variants were risk factors for thiopurine-induced leukopenia. Combined detection of the 3 variants could increase the predictive sensitivity of thiopurine-induced leukopenia and help to distinguish early leukopenia in heterozygote of c.415C>T in Chinese patients with inflammatory bowel disease. PMID: 28570428
7. Study replicated previous findings that the NUDT15 p.R139C variant is a potential predictor for AZA-induced leukopenia, extending this finding to patients with various neurological disorders in Korea and identifying its specific association with early leukopenia and severe alopecia. All of the patients who carried a NUDT15 p.R139C homozygous variant exhibited rapid development of severe leukopenia and extensive hair loss. PMID: 28566182
8. Thiopurine treatment should not be recommended to patients with NUDT15 homozygous variant genotype due to severe early leukopenia PMID: 29206869
9. All patients with both NUDT15 rs116855232 heterozygous variants and ABCC4 rs3765534 variants suffered from severe leukopenia and required 6-mercaptopurine dose reduction to less than 35 mg/m(2)/da PMID: 28883280
10. Current review highlights the scientific data on NUDT15 enzyme variant in patients with acute lymphoblastic leukaemia and its relation to 6-mercaptopurine toxicity in various ethnic populations. PMID: 28963908
11. 3 novel NUDT15 coding variants (p.R34T, p.K35E, and p.G17_V18del) in 5 children with acute lymphoblastic leukemia enrolled in frontline protocols in Singapore, Taiwan, and at St. Jude Children's Research Hospital. PMID: 28659275
12. NUDT15 variant as a predictor for thiopurine-induced toxicity in Indian patients. PMID: 27416873
13. NUDT15 gene polymorphism is related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia. PMID: 26503813
14. our results defined how NUDT15 limits thiopurine efficacy and how genetic ablation via the R139C missense mutation confers sensitivity to thiopurine treatment in patients PMID: 27530327
15. NUDT15 polymorphisms are associated with 6-mercaptopurine intolerance in children treated for acute lymphoblastic leukemia. PMID: 27577869
16. NUDT15 c.415C>T may be another predictor of AZA-induced leukocytopenia. PMID: 27381176
17. our study shows that 6-MP reduction is significant in the younger age group in relation to NUDT15 variant PMID: 27193222
18. NUDT R139C T/T genotype showed complete association with early severe hair loss/leukopenia in Japanese patients with inflammatory bowel diseases. PMID: 26076924
19. Letter: discuss role of NUDT15 in complex thiopurine metabolism. PMID: 27308664
20. There was a close association of NUDT15 R139C with early leukopenia associated with thiopurines in patients in Hong Kong PMID: 27095468
21. These results suggest that NUDT15 R139C-related thiopurine-induced leukocytopenia is mediated by a 6-TGN-independent mechanism. PMID: 26590936
22. Mutations of the NUDT15 and TPMT gene accounted for approximately 88% of cases with thiopurine-induced early leukopenia. Extensive hair loss was a recognizable early symptom in patients with the homozygous NUDT15 c.415C>T variant. PMID: 26735160
23. NUDT15 c.415C>T increases risk of 6-mercaptopurine induced myelosuppression during maintenance therapy in children with acute lymphoblastic leukemia. PMID: 26405151
24. Patients with defective NUDT15 alleles showed excessive levels of thiopurine active metabolites and toxicity. [meta-analysis] PMID: 26878724
25. Depletion of NUDT15 has no effect on incorporation of 8-oxo-dGTP into DNA and does not impact cancer cell survival in cell lines tested. NUDT15 is not a biologically relevant 8-oxo-dGTPase PMID: 26238318
26. Event-free survival did not significantly differ by NUDT15 genotype. rs116855232 is an important determinant of 6-MP myelotoxicity in Japanese children with ALL and may represent the most robust toxicity-related locus in Asians to date. PMID: 26033531
27. Describe a germline variant in NUDT15 strongly associated with mercaptopurine intolerance in childhood acute lymphoblastic leukemia, which may have implications for treatment individualization in this disease. PMID: 25624441
28. 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)). PMID: 25108385
29. human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP. PMID: 20144704
30. 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. PMID: 19419956

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HGNC: 23063

OMIM: 615792

KEGG: hsa:55270

STRING: 9606.ENSP00000258662

UniGene: Hs.144407