The NUDT15 gene helps your body handle thiopurine medicines such as azathioprine, mercaptopurine, and thioguanine. Some differences in this gene can change how your body responds to these drugs. If the gene works less well, usual doses may cause too much drug effect, which can lead to very low white blood cell counts, hair loss, mouth sores, or infections. On its own, a variant in the NUDT15 gene usually does not cause a health condition, but it can strongly affect medicine safety.
What is a gene?
Genes are segments of DNA that carry instructions your cells use to make molecules or regulate processes throughout the body. Some genes provide the information needed to produce proteins, the parts of cells that do much of the work. Other genes mainly direct when certain processes happen, where they happen, and how strongly they occur. Together, genes affect how the body develops and functions, and they can also shape how you respond to food, stress, or medications. To go into this topic in more detail, you can find more in the LearnHub.
Overview
NUDT15Gene function
What if the gene works
The NUDT15 gene helps cells break down certain drug byproducts, especially from thiopurine medicines. This lowers buildup of active compounds and helps protect DNA in fast-growing tissues like bone marrow and hair follicles.
Risk
What if the gene does not work
Milder to more severe variants in the NUDT15 gene can reduce or nearly abolish the cell’s ability to clear active thiopurine building blocks. More of these molecules may then enter DNA, especially in fast-dividing cells.
Treatment
What does that mean for your treatment
Pathogenic or loss-of-function variants in the NUDT15 gene can make thiopurine medicines, including azathioprine, mercaptopurine, and thioguanine, much harder to tolerate. Current guidelines use NUDT15 status to guide treatment, often with a much lower starting dose or a different medicine, especially if both gene copies are affected. This helps reduce the chance of severe low blood counts and hair loss.
Gene function
What if the gene works
Your cells constantly sort and reuse tiny building blocks needed for DNA and RNA. The NUDT15 gene helps keep some of these building blocks in the right chemical form, so they are used in a more controlled way. Understanding what the NUDT15 gene does in the body helps explain how cells manage everyday genetic material.
Inside your cells, the NUDT15 gene makes an enzyme that removes extra phosphate groups from certain purine building blocks (one type of DNA and RNA ingredient). This turns very active forms into less active ones that cells can handle more smoothly.
By adjusting selected building blocks before they are used, the NUDT15 gene helps control what can be added to DNA and RNA. This supports steady cell activity when cells copy DNA or make RNA.
The NUDT15 gene also acts on thiopurine forms, which are medicine related lookalikes of normal purine building blocks. It changes these highly active forms into less active ones before they are taken up into DNA or RNA.
What is a variant?
A genetic variant is a slight difference in the DNA sequence within a gene. These differences are common and are part of normal human diversity, including variation in appearance, metabolism, and the way the body reacts to environmental influences. Many do not produce any noticeable effect and simply represent natural genetic variation. At times, though, a variant changes how a gene works more significantly and can contribute to, or directly cause, a genetic condition.
Genetic variants
What if the gene does not work
Variants in the NUDT15 gene can make its protein unstable or less active, so cells clear thiopurine building blocks less effectively. That allows these compounds to build up inside cells, especially blood-forming cells. Milder and more severe variants differ in how much activity is lost. This helps explain how NUDT15 gene variants affect thiopurine response, with earlier or more marked side effects in some people.
How variants are linked to conditions
Variants in the NUDT15 gene are most strongly linked to thiopurine medicine intolerance. In people treated with azathioprine, mercaptopurine, or thioguanine, NUDT15 gene variants and thiopurine side effects are closely associated, especially very low white blood cell counts and, in some cases, hair loss. These variants do not usually cause a health condition on their own, but they can greatly increase the chance of treatment-related side effects.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are widely seen in the general population. Most do not have a direct effect on health and instead represent natural human diversity. For many genes, carrying a variant associated with a condition suggests a possible link rather than a definite diagnosis, especially when several genes and environmental influences are involved. In some situations, though, a single well-characterized variant in a particular gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For NUDT15, risk mainly changes if you take thiopurine medicines such as azathioprine, mercaptopurine, or thioguanine. People with certain NUDT15 variants, especially two changed copies, have a much higher chance of serious side effects like a sharp drop in white blood cells, and this risk also rises with higher doses.
Inheritance of NUDT15 variants
There is not a broadly confirmed Mendelian disease pattern for the NUDT15 gene, because most attention to this gene relates to how inherited variants can affect response to thiopurine medicines rather than causing a single genetic condition on their own. In practical terms, how variants of the NUDT15 gene are inherited follows the usual pattern for genes on chromosome 13: you inherit one copy from your mother and one copy from your father. A variant can be passed from either parent to a son or daughter.
What does my NUDT15 result mean for my family?
There isn’t yet a broadly confirmed inheritance pattern tied to a specific health condition for NUDT15. A NUDT15 result is most often used to understand how someone may respond to certain medicines, so what it means for family members depends on the exact result and the medicine involved.
Genetic information
Genetic testing
How you find out about variants
NUDT15 genetic testing uses a blood, saliva, or cheek swab sample to look for variants in the NUDT15 gene. This is how you find out about NUDT15 variants before starting thiopurine medicines, and results usually report whether no variant, one variant, or two variants were found.
When should I consider getting a genetic test?
Consider NUDT15 testing before starting thiopurine medicines such as azathioprine, mercaptopurine, or thioguanine, especially if you have Asian or Hispanic/Latino ancestry. It can also help explain unusually severe side effects, such as very low blood counts or major hair loss, after taking one of these medicines.
A genetic result is only one part of your health story
A genetic finding can provide useful insight, but how much it reveals depends on the condition and the kind of variant involved. Lifestyle, environment, age, and medical history, along with other factors, affect how the body works over time. For some conditions, especially those influenced by many genes, genetic information gives context rather than certainty and is most helpful when considered alongside other parts of care. In other situations, a genetic result can give a clear answer. In areas like medication response, genetic results can also help make sense of individual experiences.
Pharmacogenetics
How variants shape your response to medicine
Variants in the NUDT15 gene can strongly affect how your body handles thiopurine medicines such as azathioprine, mercaptopurine, and thioguanine. Some people with reduced NUDT15 activity are much more sensitive to these medicines and can develop very low blood counts or other side effects at usual treatment levels. This helps explain why the same medication can work differently in different people, even when they are being treated for the same condition. Genetic differences like this are common and can influence both how well a treatment works and how sensitive someone is to it.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in genes can affect the way a person responds to medications. It studies links between genes and drugs to help explain why the same treatment may work differently from one person to another. For many medicines, genes can influence how strongly a drug works or how the body handles it. This understanding can support treatment decisions that are more informed and more individualized. If you want to learn more about this topic, you can explore it further in the LearnHub.
Drugs influenced by the NUDT15 gene
When should I seek medical advice?
Talk with your doctor about NUDT15 before starting or changing thiopurine medicines, a group used for some cancers and some immune-related conditions. Some people with changes in NUDT15 break down these medicines differently and can have a much higher risk of serious side effects, especially a big drop in white blood cells. Get medical advice promptly during treatment if fever, mouth sores, unusual bruising, or severe tiredness appear.
History
NUDT15 entered medical genetics more recently than many well known genes, as researchers worked to explain why some people had unexpectedly strong side effects from thiopurine medicines. Early studies in East Asian populations helped bring this gene to attention because certain NUDT15 variants were found much more often in people who developed marked treatment related toxicity. From these first observations, research expanded steadily. Scientists then confirmed the gene’s importance in other groups, including Hispanic and Latino populations, and it became part of the growing field of pharmacogenetics. In recent decades, awareness of this gene’s role has grown as testing before thiopurine treatment became more common in some settings. That shift helped move care toward more personalized prescribing.