MCID: THP005
MIFTS: 12

Thiopurines, Poor Metabolism of, 2

Categories: Genetic diseases, Metabolic diseases

Aliases & Classifications for Thiopurines, Poor Metabolism of, 2

MalaCards integrated aliases for Thiopurines, Poor Metabolism of, 2:

Name: Thiopurines, Poor Metabolism of, 2 57 6
Nudt15 Deficiency 57
Thpm2 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
increased susceptibility to toxic effects of treatment with thiopurines
nudt15 genetic variation is over represented in asians
some haplotypes confer more sensitivity to mercaptopurine than others
homozygous carriers can tolerate <10% of the standard dosage


HPO:

32
thiopurines, poor metabolism of, 2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 616903
MedGen 42 C4225160
SNOMED-CT via HPO 69 263681008

Summaries for Thiopurines, Poor Metabolism of, 2

OMIM : 57 THPM2 is associated with severe hematopoietic toxicity when patients are treated with standard doses of thiopurines, a class of antineoplastic/immunosuppressant agents that consists of mercaptopurine, thioguanine, and azathioprine. Thiopurines are prodrugs that require extensive metabolism in order to exert their cytotoxic action. Thiopurines are converted into cytotoxic thioguanine nucleotides (TG), which are incorporated into DNA and cause cell death. NUDT15 inactivates thiopurine metabolites and negatively regulates cytotoxicity (summary by Moriyama et al., 2016). The NUDT15 deficiency trait follows an additive genetic mode of inheritance, with the severity of the phenotype proportional to the cumulative number of risk alleles in NUDT15. For a discussion of genetic heterogeneity of poor thiopurine metabolism, see THPM1 (610460). (616903)

MalaCards based summary : Thiopurines, Poor Metabolism of, 2, is also known as nudt15 deficiency. An important gene associated with Thiopurines, Poor Metabolism of, 2 is NUDT15 (Nudix Hydrolase 15).

Related Diseases for Thiopurines, Poor Metabolism of, 2

Diseases in the Thiopurines, Poor Metabolism of, 1 family:

Thiopurines, Poor Metabolism of, 2

Symptoms & Phenotypes for Thiopurines, Poor Metabolism of, 2

Symptoms via clinical synopsis from OMIM:

57
Hematology:
myelosuppression develops on standard doses of thiopurine drugs
hematopoietic toxicity develops on standard doses of thiopurine drugs

Laboratory Abnormalities:
decreased activity of nudt15
decreased metabolism of thiopurine drugs
increased toxic thioguanine nucleotides (tgns) on standard doses of thiopurine drugs


Clinical features from OMIM:

616903

Drugs & Therapeutics for Thiopurines, Poor Metabolism of, 2

Search Clinical Trials , NIH Clinical Center for Thiopurines, Poor Metabolism of, 2

Genetic Tests for Thiopurines, Poor Metabolism of, 2

Anatomical Context for Thiopurines, Poor Metabolism of, 2

Publications for Thiopurines, Poor Metabolism of, 2

Variations for Thiopurines, Poor Metabolism of, 2

ClinVar genetic disease variations for Thiopurines, Poor Metabolism of, 2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NUDT15 NM_018283.3(NUDT15): c.415C> T (p.Arg139Cys) single nucleotide variant drug response rs116855232 GRCh37 Chromosome 13, 48619855: 48619855
2 NUDT15 NM_018283.3(NUDT15): c.415C> T (p.Arg139Cys) single nucleotide variant drug response rs116855232 GRCh38 Chromosome 13, 48045719: 48045719
3 NUDT15 NM_018283.3(NUDT15): c.416G> A (p.Arg139His) single nucleotide variant drug response rs147390019 GRCh38 Chromosome 13, 48045720: 48045720
4 NUDT15 NM_018283.3(NUDT15): c.416G> A (p.Arg139His) single nucleotide variant drug response rs147390019 GRCh37 Chromosome 13, 48619856: 48619856
5 NUDT15 NM_018283.3(NUDT15): c.52G> A (p.Val18Ile) single nucleotide variant drug response rs186364861 GRCh37 Chromosome 13, 48611934: 48611934
6 NUDT15 NM_018283.3(NUDT15): c.52G> A (p.Val18Ile) single nucleotide variant drug response rs186364861 GRCh38 Chromosome 13, 48037798: 48037798
7 NUDT15 NM_018283.3(NUDT15): c.50_55dupGAGTCG (p.Val18_Val19insGlyVal) duplication drug response rs869320766 GRCh37 Chromosome 13, 48611932: 48611937
8 NUDT15 NM_018283.3(NUDT15): c.50_55dupGAGTCG (p.Val18_Val19insGlyVal) duplication drug response rs869320766 GRCh38 Chromosome 13, 48037796: 48037801

Expression for Thiopurines, Poor Metabolism of, 2

Search GEO for disease gene expression data for Thiopurines, Poor Metabolism of, 2.

Pathways for Thiopurines, Poor Metabolism of, 2

GO Terms for Thiopurines, Poor Metabolism of, 2

Sources for Thiopurines, Poor Metabolism of, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
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40 LOVD
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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