Understanding Your TPMT and NUDT15 Test Results

Section Editors: Christopher McCudden Ph.D., DABCC, FADLM, FCACB and Kamran Mirza MD PhD
July 6, 2026

TPMT and NUDT15 are two genes that carry the instructions for making enzymes your body uses to break down a group of medications called thiopurines. Thiopurines include azathioprine, mercaptopurine (also written 6-MP), and thioguanine. These medications are used to treat several conditions, including inflammatory bowel disease, some autoimmune diseases, and certain types of leukemia. The TPMT and NUDT15 test looks at these two genes to predict how well your body can clear thiopurine drugs. This information helps your care team choose a safe starting dose before you begin treatment.

This article explains what the test measures, what each possible result means, and how those results are used to guide your care. A result from this test is not a diagnosis of any disease. It is information about how your body is likely to respond to a specific group of medications.

This test does not report a number or a reference range. It reports a category that describes how your body is expected to process thiopurine medications, such as “normal metabolizer,” “intermediate metabolizer,” or “poor metabolizer.” Because the result reflects genes you were born with, it does not change over time and usually only needs to be tested once. What a given result means for your dose depends on which medication you are taking and the condition being treated, and those decisions are made by the doctor who prescribes the medication. Always discuss your result with your care team.

What do TPMT and NUDT15 do?

TPMT stands for thiopurine methyltransferase, and NUDT15 stands for nudix hydrolase 15. Each is a gene that provides the instructions for making an enzyme of the same name. An enzyme is a protein that carries out a specific chemical job in the body. The job of the TPMT and NUDT15 enzymes is to help regulate how the body processes thiopurine medications, including azathioprine, mercaptopurine (6-MP), and thioguanine.

When you take a thiopurine, your body converts it into active substances called thioguanine nucleotides. These active substances are what make the medication work, but if too much builds up, they can also harm healthy cells. The TPMT and NUDT15 enzymes act as brakes on this process, keeping the amount of the active substance within a safe range. People who inherit certain changes, called variants, in the TPMT or NUDT15 gene make less of the working enzyme, or none at all. With weaker brakes, the active substances build up to higher-than-intended levels.

The main risk from this buildup is myelosuppression, which means the bone marrow slows down its production of blood cells. Because the bone marrow makes red blood cells, white blood cells, and platelets, myelosuppression can lead to a low white blood cell count (raising the risk of infection), a low platelet count (raising the risk of bleeding), and a low red blood cell count (anemia, which can cause fatigue). Severe myelosuppression can be dangerous. Testing TPMT and NUDT15 before starting a thiopurine helps identify people who are more likely to have this reaction, so the dose can be adjusted in advance.

Which medications and conditions does this test apply to?

The TPMT and NUDT15 test applies to the three thiopurine medications: azathioprine, mercaptopurine (6-MP), and thioguanine. These drugs are used across a wide range of conditions, and most people who have this test do not have cancer. Thiopurines are commonly prescribed for inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), autoimmune conditions such as autoimmune hepatitis, lupus, and some forms of vasculitis, and to help prevent rejection after an organ transplant. Mercaptopurine and thioguanine are also an important part of long-term (maintenance) treatment for acute lymphoblastic leukemia (ALL), a blood cancer that is most common in children.

Because all of these treatments rely on thiopurines and thiopurine toxicity can affect anyone, regardless of the condition being treated, the same TPMT and NUDT15 results are useful no matter why the medication is being prescribed.

How is the test performed?

The TPMT and NUDT15 test is usually performed on a small blood sample, although some laboratories can also use a cheek swab. The sample is sent to a laboratory, where the DNA is analyzed to look for known variants in the TPMT and NUDT15 genes. Because these genes are inherited and do not change during your life, the test generally only needs to be done once. The result stays valid for any future thiopurine prescription.

It is helpful to know that laboratories test for the most common variants known to reduce enzyme activity, not every possible change in these genes. This means a “normal metabolizer” result lowers the chance of a serious reaction but does not remove it completely, because a rare variant that the test does not check for could still be present. For this reason, blood counts are still monitored after starting a thiopurine even when the test result is normal. This same principle applies to other pharmacogenomic tests, such as the DPYD test used before certain chemotherapy drugs.

What do the results mean?

The TPMT and NUDT15 test reports a separate result for each gene. Each result places you into one of three categories, called a metabolizer status or phenotype, based on the variants found. Your report will name one category for TPMT and one for NUDT15, for example “TPMT Normal Metabolizer” and “NUDT15 Intermediate Metabolizer.” The categories describe how much working enzyme you are expected to have, which in turn predicts how likely thiopurine medications are to build up.

TPMT results

TPMT normal metabolizer — Both copies of the TPMT gene work normally, so the enzyme is fully active. Thiopurine medications are expected to be processed as usual, and no dose change is needed because of TPMT. This is the most common result in most populations.
TPMT intermediate metabolizer — One copy of the gene carries a variant that reduces or abolishes enzyme activity, while the other copy functions normally. Enzyme activity is reduced, so active substances build up somewhat more than usual, and the risk of low blood counts is higher. A lower starting dose is often considered for this result.
TPMT poor metabolizer — Both copies of the gene carry variants that reduce or abolish enzyme activity, so there is little or no functional enzyme. Active substances can build up to very high levels, and the risk of severe myelosuppression is high. For this result, the prescriber usually considers a large dose reduction or a medication that does not depend on TPMT.

NUDT15 results

NUDT15 normal metabolizer — Both copies of the NUDT15 gene work normally, and the enzyme is fully active. Thiopurine medications are expected to be processed as usual, and no dose change is needed because of NUDT15.
NUDT15 intermediate metabolizer — One copy of the gene carries a variant that reduces or abolishes enzyme activity. Enzyme activity is reduced, active substances build up somewhat more than usual, and the risk of low blood counts is higher. A lower starting dose is often considered for this result.
NUDT15 poor metabolizer — Both copies of the gene carry variants that reduce or abolish enzyme activity, so there is little or no functional enzyme. The risk of severe myelosuppression is high, and the prescriber usually considers a large dose reduction or an alternative medication.

Some reports use the term possible intermediate metabolizer. This is used when one of the variants found has an uncertain effect on enzyme activity. In practice, a possible intermediate metabolizer is treated the same way as an intermediate metabolizer, with a lower starting dose considered.

When both genes are considered together

Because TPMT and NUDT15 both affect the same medications, the prescriber looks at both results together when choosing a dose. A useful way to think about the combination is:

Normal for both genes — Standard dosing is expected to be appropriate, with routine blood count monitoring.
Intermediate for one gene, normal for the other — A reduced starting dose is often considered.
Intermediate for both genes — This combination is sometimes called a compound intermediate metabolizer. Having reduced activity in both enzymes at once adds up, so a larger dose reduction is considered than for a single intermediate result.
Poor metabolizer for either gene — This is treated as a high-risk result. The prescriber usually considers a substantial dose reduction or a medication that does not rely on the affected enzyme, regardless of the other gene’s result.

The exact dose adjustment also depends on the specific thiopurine being used and the condition being treated. For these reasons, the test result guides the decision but does not set a fixed dose on its own. Your care team combines the result with your diagnosis, the chosen medication, and your overall health.

Why your ancestry can affect these results

Variants in TPMT and NUDT15 are found in people of all backgrounds, but they occur at different rates across populations. Variants that reduce TPMT activity are more common in people of European and African ancestry, while variants that reduce NUDT15 activity are more common in people of East Asian, South Asian, and Hispanic or Latino ancestry. As a rough guide, being a poor metabolizer for TPMT is uncommon (fewer than 1 in 200 people of European or African ancestry), while carrying a single reduced-activity TPMT variant (an intermediate metabolizer result) is seen in roughly 1 in 10 people of European ancestry. For NUDT15, poor metabolizer results are rare in people of European or African ancestry but are found in about 2 in 100 people of East Asian ancestry, and intermediate results are more common still in East Asian, South Asian, and Hispanic or Latino populations.

Because either gene can carry an important variant, and because many people have mixed or uncertain ancestry, both genes are tested for everyone rather than choosing one based on background. This gives the most complete picture of thiopurine safety.

What happens after the test?

The results of the TPMT and NUDT15 tests are used to guide the dose your care team selects and are part of a larger plan. A normal result in both genes supports starting at a standard dose. An intermediate or poor metabolizer result in either gene may lead the prescriber to start at a lower dose or to consider a different medication, based on the specific drug and condition. Whatever the result, blood counts are checked regularly after starting a thiopurine, most often with a complete blood count (CBC), so that any drop in blood cells can be caught early and the dose adjusted if needed.

Because these results reflect inherited genes, they can also be relevant to your biological relatives, who may carry the same variants. Family members who are considering a thiopurine medication can mention your result to their own doctors and ask whether testing is right for them. It is a good idea to keep a record of your TPMT and NUDT15 result and to share it with any doctor who may prescribe these medications in the future.

One point can cause confusion. In the past, some laboratories tested only TPMT, because the role of NUDT15 was recognized more recently. If you were tested years ago, your record may show a TPMT result but no NUDT15 result. The current test checks both genes together. Your care team can advise whether an older TPMT-only result is sufficient for your situation or whether NUDT15 testing would add useful information.

Questions to ask your doctor

What were my TPMT and NUDT15 results, and what category did each fall into?
Based on my results, will my thiopurine medication be started at a standard or a reduced dose?
Is a thiopurine still the best choice for me, or should an alternative medication be considered?
How often will my blood counts be checked after I start treatment?
What symptoms of low blood counts should I watch for and report right away?
Does my result mean my biological relatives should consider testing?
Could a rare variant that the test does not check for still affect me?
If I was tested for TPMT in the past, do I also need testing for NUDT15?
How should I keep a record of this result for future prescriptions?
Who should I contact if I have side effects after starting the medication?