Haplotype
TPMT *3A with related variants rs1142345 rs1800460

Clinical Annotations

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

View the full haplotype translation table for TPMT

Variant Alelle
rs1800462
rs1142345 C (differs from reference)
rs1800460 T (differs from reference)
rs1800584
rs72552739
rs72552740
rs75543815
rs72552736
rs56161402
rs151149760
rs72552737
rs72552738
TPMT 374C>T
rs72552742
rs9333569
rs9333570
rs144041067
TPMT 124C>G
TPMT 211G>A
TPMT 106G>A
rs150900439
rs200591577
TPMT 488G>C
rs74423290
rs6921269
TPMT 634T>C
rs3931660
rs12529220
rs2518463
rs2842934
TPMT minus 178C>T
TPMT 365A>C
rs72556347
TPMT 319T>G
TPMT 349G>C
rs267607275
rs79901429
rs115106679
rs112339338
rs111901354
TPMT 200T>C
TPMT 595G>A
rs398122996

Haplotype Annotations

PharmGKB haplotype annotations provide information about haplotype-drug pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.

Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.

There are direct annotations for this haplotype. Register or sign in to see them.

VIP Annotation

This haplotype contains two nonsynonymous SNPs, *3B and *3C, and is the most common TPMT variation occuring in the Caucasian population. The haplotype results in significant decreases in TPMT enzymatic activity resulting in toxicity when thiopurine therapy is administered.

Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism [Article:8561894] .
Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians PMID 8644731.

Note: The TPMT gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.

Key Publications:
  1. Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. American journal of human genetics. 1996. Tai H L, Krynetski E Y, Yates C R, Loennechen T, Fessing M Y, Krynetskaia N F, Evans W E. PubMed