NUDT15 (13q14.2), MTH2D, Nucleotide triphosphate difosfataasi

https://www.ncbi.nlm.nih.gov/gene/55270
Obs: Thiopurine induced leukemia 

Also known as

MTH2; NUDT15D

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]

Expression

Ubiquitous expression in colon (RPKM 4.7), duodenum (RPKM 4.1) and 25 other tissues See more

Preferred Names

nucleotide triphosphate diphosphatase NUDT15

Names

8-oxo-dGTPase NUDT15

mutT homolog 2

nucleoside diphosphate-linked to another moiety X hydrolase 15

nudix (nucleoside diphosphate linked moiety X)-type motif 15

probable 7,8-dihydro-8-oxoguanine triphosphatase NUDT15

probable 8-oxo-dGTP diphosphatase NUDT15

NP_001291674.1

• EC 3.6.1.9

Related articles in PubMed

1. Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines. Kojima Y, et al. World J Gastroenterol, 2018 Jan 28. PMID 29398872, Free PMC Article
2. Predictive role of NUDT15 variants on thiopurine-induced myelotoxicity in Asian inflammatory bowel disease patients. Sutiman N, et al. Pharmacogenomics, 2018 Jan. PMID 29210335,
3. Emerging role of NUDT15 polymorphisms in 6-mercaptopurine metabolism and dose related toxicity in acute lymphoblastic leukaemia. Singh M, et al. Leuk Res, 2017 Nov. PMID 28963908
4. NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia. Yi ES, et al. Cancer Res Treat, 2018 Jul. PMID 28903549, Free PMC Article
5. Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry. Moriyama T, et al. Blood, 2017 Sep 7. PMID 28659275, Free PMC Article

See all (42) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

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.
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.
3. Mutations in exon 1 of NUDT15 also affect thiopurine-induced leukopenia in patients with inflammatory bowel disease.
4. With increasing copy numbers of the risk T allele at NUDT15.
5. results of this meta-analysis confirm that NUDT15 c.415C>T may be an important predictor of thiopurine-induced leukocytopenia in Asians
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.
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.
8. Thiopurine treatment should not be recommended to patients with NUDT15 homozygous variant genotype due to severe early leukopenia
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
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.

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