|(A;A)||0||common in clinvar|
|(A;G)||3||TPMT*3C . impaired drug metabolism|
|(G;G)||3.5||possibly incapable of detoxifying certain drugs|
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.
|Disease||Thiopurine methyltransferase deficiency|
|CLNDBN||Thiopurine methyltransferase deficiency|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
[PMID 18547414] Genotyping panel for assessing response to cancer chemotherapy.
[PMID 18662289] Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.
[PMID 18685564] Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.
|qualified_impact||Low clinical importance, pharmacogenetic|
|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 23133420] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.