NUDT15

NUDT15
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5BON
Identifiers
Aliases	NUDT15, MTH2, NUDT15D, nudix hydrolase 15
External IDs	OMIM: 615792; MGI: 2443366; HomoloGene: 10109; GeneCards: NUDT15; OMA:NUDT15 - orthologs
Gene location (Human)
Chr.	Chromosome 13 (human)
End	48,047,221 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	73,785,682 bp
RNA expression pattern
	Top expressed in
	gonad; ; endothelial cell; ; mucosa of transverse colon; ; oocyte; ; rectum; ; secondary oocyte; ; mucosa of sigmoid colon; ; palpebral conjunctiva; ; gingival epithelium; ; endometrium;
	Top expressed in
	spermatocyte; ; muscle of thigh; ; morula; ; embryo; ; ventricular zone; ; embryo; ; tail of embryo; ; renal corpuscle; ; epiblast; ; neural tube;
	More reference expression data
	n/a
Gene ontology
Molecular function	8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity; hydrolase activity; metal ion binding; 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity; nucleoside-diphosphatase activity; nucleotide diphosphatase activity; protein binding; NADH pyrophosphatase activity; nucleoside-triphosphate diphosphatase activity;
Cellular component	cytosol;
Biological process	nucleobase-containing small molecule catabolic process; dGTP catabolic process; mitotic cell cycle; purine nucleotide catabolic process; DNA protection; regulation of proteasomal protein catabolic process; nucleoside phosphate catabolic process; response to reactive oxygen species; purine deoxyribonucleoside triphosphate catabolic process;
	Sources:Amigo / QuickGO
Orthologs
	55270
	214254
	ENSG00000136159
	ENSMUSG00000033405
	Q9NV35
	Q8BG93
	NM_018283; NM_001304745
	NM_172527; NM_001360484
	NP_001291674; NP_060753
	NP_766115; NP_001347413
	Wikidata
View/Edit Human	View/Edit Mouse

Nudix hydrolase 15 is a protein that in humans is encoded by the NUDT15 gene.^[5]

Function

The NUDT15 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.

NUDT15 germline variants (e.g., a missense SNP:rs116855232, inducing R139C) have been linked to clinical usage of thiopurines (e.g., mercaptopurine) in acute lymphoblastic leukemia^[6]^[7] as well as inflammatory bowel diseases to avoid thiopurine-induced leukopenia.^[8]^[9] These variants also exhibit ethnicity-specific (e.g., variant allele of rs116855232 is high is East Asians and Hispanics but low in Caucasians and Africans). Rare functional variants in this gene have also been identified as being related to thiopurine-induced myelotoxicity,^[10] suggesting the whole gene screening should be taken to determine the initial dosage using of thiopurine.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000136159 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000033405 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: Nudix hydrolase 15".
^ Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, Zhao X, et al. (April 2016). "NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity". Nature Genetics. 48 (4): 367–73. doi:10.1038/ng.3508. PMC 5029084. PMID 26878724.
^ Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, et al. (April 2015). "Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia". Journal of Clinical Oncology. 33 (11): 1235–42. doi:10.1200/JCO.2014.59.4671. PMC 4375304. PMID 25624441.
^ Yang SK, Hong M, Baek J, Choi H, Zhao W, Jung Y, et al. (September 2014). "A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia". Nature Genetics. 46 (9): 1017–20. doi:10.1038/ng.3060. PMC 4999337. PMID 25108385.
^ Yin D, Xia X, Zhang J, Zhang S, Liao F, Zhang G, et al. (February 2017). "Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose". Oncotarget. 8 (8): 13575–13585. doi:10.18632/oncotarget.14594. PMC 5355121. PMID 28088792.
^ Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al. (September 2017). "Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry". Blood. 130 (10): 1209–1212. doi:10.1182/blood-2017-05-782383. PMC 5606007. PMID 28659275.

External links

Overview of all the structural information available in the PDB for UniProt: Q9NV35 (Nucleotide triphosphate diphosphatase NUDT15) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on human chromosome 13 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000136159 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000033405 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: Nudix hydrolase 15".

[6] Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, Zhao X, et al. (April 2016). "NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity". Nature Genetics. 48 (4): 367–73. doi:10.1038/ng.3508. PMC 5029084. PMID 26878724.

[7] Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, et al. (April 2015). "Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia". Journal of Clinical Oncology. 33 (11): 1235–42. doi:10.1200/JCO.2014.59.4671. PMC 4375304. PMID 25624441.

[8] Yang SK, Hong M, Baek J, Choi H, Zhao W, Jung Y, et al. (September 2014). "A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia". Nature Genetics. 46 (9): 1017–20. doi:10.1038/ng.3060. PMC 4999337. PMID 25108385.

[9] Yin D, Xia X, Zhang J, Zhang S, Liao F, Zhang G, et al. (February 2017). "Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose". Oncotarget. 8 (8): 13575–13585. doi:10.18632/oncotarget.14594. PMC 5355121. PMID 28088792.

[10] Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al. (September 2017). "Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry". Blood. 130 (10): 1209–1212. doi:10.1182/blood-2017-05-782383. PMC 5606007. PMID 28659275.

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NUDT15

Contents

Function

References

Further reading

External links