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Thiopurine Methyltransferase (TPMT) and Medicines

What is TPMT? 

When you take a medicine, your body needs a way to handle it. One way is for enzymes to metabolize (break down) the medicine. An enzyme called thiopurine methyltransferase (TPMT) can break down a class of medicines called thiopurines. Thiopurines include mercaptopurine (6-MP, Purinethol®), thioguanine (6-TG, Tabloid®), and azathioprine (Imuran®).  

Thiopurine medicines 

Mercaptopurine and thioguanine are important chemotherapy medicines used to treat leukemia. Azathioprine is a medicine used to treat some autoimmune diseases. Like many medicines, how well thiopurines work and their side effects can be different from person to person.

TPMT function 

Most people have no problem breaking down thiopurines. However, a small number of people (about 1 in 300) have almost no ability to break down these medicines. For these people, toxic levels of the medicine build up in the body. People with no TPMT enzyme function can have very serious side effects such as low blood counts or infection if they receive normal doses of thiopurine medicines.   

Pharmacogenomic testing 

Each person differs from another at the DNA level. Genes are segments of DNA that act as a set of instructions and tell the body how to work. The TPMT gene is a section of DNA that instructs how well TPMT enzymes will work.  

The study of how genes like TPMT affect the way your body interacts with medicines is called pharmacogenomics. Differences in your DNA that make up the TPMT gene can change how well you are able to break down thiopurine medicines such as mercaptopurine, thioguanine, or azathioprine.  

A pharmacogenomic test looks for differences that can help your medical team know how well your TPMT enzymes will work. The test results can help your doctor and pharmacist choose the correct dose of medicine to give you.  

TPMT gene groups 

The results of your TPMT pharmacogenomic test will place you into one of three groups: 

Normal metabolizer – People in this group have normal TPMT function. About 90 in 100 people are in this group.  

Intermediate metabolizer – People in this group have slightly reduced TPMT function. They may need lower doses of thiopurine medicines to avoid side effects. About 10 in 100 people are in this group. 

Poor metabolizer – People in this group have no TPMT enzyme. These patients are at high risk for having side effects, including very low blood counts that could be life threatening. Patients should receive much lower than normal doses of mercaptopurine, thioguanine, or azathioprine. About 1 in 300 people are in this group. 

A second enzyme called nudix-type motif 15 (NUDT15) is important to break down thiopurine medicines. You may also be tested for the NUDT15 gene. For more information, see TPMT & NUDT15 and Medicines.   

Scientists continue to find new information about which medicines are affected by gene test results. Talk to your doctor or pharmacist if you have questions about your medicines, side effects, or pharmacogenomic testing.  

Find more information about genes that are being used to make medication therapy decisions for patients at St. Jude.   

If you have questions about pharmacogenomic testing done at St. Jude, you can email the Clinical Pharmacogenomics Program at

Key points about TPMT

  • TPMT is an enzyme that help the body break down medicines called thiopurines.   
  • People who are poor metabolizers are at risk for serious side effects if they take normal doses of thiopurines. 
  • Pharmacogenomic testing can help identify people who are intermediate or poor metabolizers. This helps doctors and pharmacists know ahead of time whether to prescribe lower doses of medicine. 

Reviewed: October 2022