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rs1142345

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(A;A) 0 common in clinvar
(A;G) 3 TPMT*3C . impaired drug metabolism
(G;G) 3.5 possibly incapable of detoxifying
ReferenceGRCh38 38.1/142
Chromosome6
Position18130687
GeneTPMT
is asnp
is mentioned by
dbSNPrs1142345
ebirs1142345
HLIrs1142345
Exacrs1142345
Varsomers1142345
Maprs1142345
PheGenIrs1142345
hapmaprs1142345
1000 genomesrs1142345
hgdprs1142345
ensemblrs1142345
gopubmedrs1142345
geneviewrs1142345
scholarrs1142345
googlers1142345
pharmgkbrs1142345
gwascentralrs1142345
openSNPrs1142345
23andMers1142345
23andMe allrs1142345
SNP Nexus

SNPshotrs1142345
SNPdbers1142345
MSV3drs1142345
GWAS Ctlgrs1142345
GMAF0.04591
Max Magnitude3.5
? (A;A) (A;G) (G;G) 28
CPMC Logo.png

This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB.
Additional information is available here

rs1142345 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced.

The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460(A) SNP, the allele is actually a TPMT*3A allele (OMIM).

The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment.

23andMe blog hearing loss linked to a chemotherapy drug named Cisplatin.

[wikipedia] thiopurine drugs metabolized by TPMT include azathioprine, mercaptopurine, and thioguanine



OMIM187680
Desc
Variant0002
Relatedalso
OMIM187680
Desc
Variant0005
Relatedalso


ClinVar
Risk rs1142345(C;C)
Alt rs1142345(C;C)
Reference rs1142345(A;A)
Significance Drug-response
Disease Thiopurine methyltransferase deficiency
Variation info
Gene TPMT
CLNDBN Thiopurine methyltransferase deficiency
Reversed 1
HGVS NC_000006.11:g.18130918T>C
CLNSRC OMIM Allelic Variant
CLNACC RCV000013559.24, RCV000013562.24,



[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.


[PMID 18662289OA-icon.png] Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.


[PMID 18685564OA-icon.png] Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.


GET Evidence
TPMT-Y240C
aa_change Tyr240Cys
aa_change_short Y240C
impact pharmacogenetic
qualified_impact Low clinical importance, pharmacogenetic
overall_frequency 0.0461825
summary Alone, this variant is known as TPMT*3C -- but often, especially in Caucasians, it is found together with another nonsynonymous variant (A154T) to produce the TPMT*3A variant. Both variants are associated with loss of thiopurine methyltransferase (TPMT) activity, although *3C is milder than *3A. Inability to metabolize thiopurine drugs can lead to severe adverse reactions. Heterozygotes may be advised to take a reduced dosage due to reduced metabolism of the drug.



[PMID 23133420OA-icon.png] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.