part of TPMT Nomenclature Committee Haplotype Set

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.

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HGVS representation NC_000006.12:g.[18130918T>C;18139228C>T]
Translation Table This haplotype is part of the set "TPMT Nomenclature Committee Haplotype Set". There is a full translation table for TPMT Nomenclature Committee Haplotype Set

Download Translation Table


Any chromosomal positions listed below are assumed to be on the GRCh38 assembly. Be aware, the assembly may differ for variants elsewhere on the PharmGKB site.

Variant Location Allele Reference Allele
rs1142345 C T
rs1800460 T C

Variant Annotations

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.

List of all variant annotations for TPMT*3A

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