THPM2
MCID: THP005
MIFTS: 18

Thiopurines, Poor Metabolism of, 2 (THPM2)

Categories: Blood diseases, Bone diseases, Cancer diseases, Genetic diseases, Immune 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 56 29 6
Nudt15 Deficiency 56
Thpm2 56

Characteristics:

OMIM:

56
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:

31
thiopurines, poor metabolism of, 2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 56 616903
OMIM Phenotypic Series 56 PS610460
MedGen 41 C4225160
SNOMED-CT via HPO 68 263681008

Summaries for Thiopurines, Poor Metabolism of, 2

OMIM : 56 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). Affiliated tissues include bone.

Wikipedia : 74 Nudix hydrolase 15 is a protein that in humans is encoded by the NUDT15... more...

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:

56
Hematology:
myelosuppression develops on standard doses of thiopurine drugs
hematopoietic toxicity develops on standard doses of thiopurine drugs

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

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

Genetic tests related to Thiopurines, Poor Metabolism of, 2:

# Genetic test Affiliating Genes
1 Thiopurines, Poor Metabolism of, 2 29 NUDT15

Anatomical Context for Thiopurines, Poor Metabolism of, 2

MalaCards organs/tissues related to Thiopurines, Poor Metabolism of, 2:

40
Bone

Publications for Thiopurines, Poor Metabolism of, 2

Articles related to Thiopurines, Poor Metabolism of, 2:

# Title Authors PMID Year
1
NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. 56 6
26878724 2016
2
A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. 56 6
25108385 2014
3
The effects of inherited NUDT15 polymorphisms on thiopurine active metabolites in Japanese children with acute lymphoblastic leukemia. 61
28445187 2017

Variations for Thiopurines, Poor Metabolism of, 2

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

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NUDT15 NM_018283.4(NUDT15):c.415C>T (p.Arg139Cys)SNV drug response 225201 rs116855232 13:48619855-48619855 13:48045719-48045719
2 NUDT15 NM_018283.4(NUDT15):c.416G>A (p.Arg139His)SNV drug response 225202 rs147390019 13:48619856-48619856 13:48045720-48045720
3 NUDT15 NM_018283.4(NUDT15):c.52G>A (p.Val18Ile)SNV drug response 225203 rs186364861 13:48611934-48611934 13:48037798-48037798
4 NUDT15 NM_018283.4(NUDT15):c.38_43GAGTCG[4] (p.13_14GV[4])short repeat drug response 225204 rs746071566 13:48611918-48611919 13:48037782-48037783

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 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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