Table 4.
List of allele variants at the human TPMT locus.
| Locus | SNP | Location | Enzyme activity |
|---|---|---|---|
| TPMT*1 | Wild type: high activity | ||
| TPMT*1A | C178T | Exon 1 | Higher enzymatic activity [142] |
| TPMT*2 (the 1st identified variant allele) | G238C (Ala80Pro) | Exon 5 | This mutation led to a 100-fold reduction in TPMT activity and very low levels of immunodetectable protein [137] |
| TPMT*3A (contains two transition mutations, *3B and *3C) | G460A (Ala154Thr) and A719 G (Tyr240Cys) | Exon 7 and 10 | The most common variant allele responsible for low TPMT activity in Caucasians; 400-fold decrease in protein levels and no detectable enzyme activity [139] |
| TPMT*3B | G460A (Ala154Thr) | Exon 7 | Four-fold decrease in protein levels |
| TPMT*3C | A719 G (Tyr240Cys) | Exon 10 | More frequently identified in African and Southeast Asian populations; 1.4-fold reduction in protein level and associated with lower immunodetectable TPMT protein and catalytic activity [140] |
| TPMT*3D | G292 T/G460A (Glu-Stop) | Exon 5 and 7 | Formation of a premature stop codon [143,144] |
| TPMT*4 | G to A transition | Intron 9–exon 10 junction | Destruction of a splice site [141], with reduced TPMT activity |
| TPMT*5 | T146C (Leu49Ser) | Exon | Intermediate TPMT activity [145] |
| TPMT*6 | A539 T (Tyr180Phe) | Exon 8 | Korean subject with intermediate activity [145] |
| PMT*7 | T681 G (His227Glu) | Exon 10 | European subject with intermediate TPMT activity |
| TPMT*8 | G644A (Arg215His) | Exon 10 | African American subject with intermediate activity [146] |
| TPMT*9 | A356C (Lys119Thr) | Exon | No function [147] |
| TPMT*10 | G430C (Gly144Arg) | Exon | Deficient activity |
| TPMT*11 | G395A (Cys132Tyr) | Exon | No function |
| TPMT*12 | C374 T (Ser125Leu) | Exon | No function |
| TPMT*13 | A83 T (Glu28Val) | Exon | No function |
| TPMT*14 | A1G (Met1Val),-G1A, | Exon 3 | Splicing defect [148] |
| TPMT*15 | G488A (Arg163His), | Intron 7 | |
| TPMT*16 | C124 G (Gln42Glu), | Exon | |
| TPMT*17 | G211A (Gly71Arg) | Exon | |
| TPMT*18 | Exon | ||
| TPMT*1S | T474C | Exon | Silent mutation that does not lead to any change in enzymatic activity [149] |
| TPMT*45 | C676 T (Pro226*) | Exon | nonsense mutation that decreased TPMT activity [134] |