TPMT rs9333569: Understanding This Rare Genetic Variant
The rs9333569 variant is a rare genetic change located within the TPMT gene. It has been identified in pharmacogenomic research as a potential marker related to metabolic processing and stress-response pathways.
What each genotype means
Likely typical enzyme activity
This is the most common genotype, often referred to as the wild-type or *1/*1 state. Research indicates that individuals with this genotype typically have normal Thiopurine S-methyltransferase (TPMT) enzyme activity. If you are prescribed thiopurine medications, such as azathioprine or mercaptopurine, discuss your treatment plan with your clinician or pharmacist to ensure appropriate dosing.
This genotype is the most frequent in all major human populations.
Potential for altered enzyme activity
This genotype represents a heterozygous state, where one copy of the gene carries the T allele and the other carries the C allele. This specific variant (sometimes associated with the TPMT*15 allele) may be linked to variations in enzyme function, though the clinical significance of this specific SNP is limited compared to major variants like *2 or *3A. Because thiopurine medications require careful dosing based on your metabolic capacity, please consult your healthcare provider or pharmacist regarding any current or future thiopurine therapy.
This is a rare genotype; exact frequencies vary by ancestry but are generally low across global populations.
Potential for reduced enzyme activity
This genotype indicates that both copies of the gene carry the C variant. While research on this specific variant is limited, carrying two copies of a non-reference allele in the TPMT gene can be associated with reduced or altered metabolic processing of thiopurine medications. It is important to discuss this result with your clinician or pharmacist, especially if you are taking or considering medications that are metabolized by the TPMT enzyme.
This genotype is extremely rare in all known human populations.
What is rs9333569 and Where is it Located?
The rs9333569 variant is a specific change in the DNA sequence of the TPMT gene, which is located on chromosome 6. In genetic databases, this variant is categorized as a missense mutation, meaning the change in the DNA code results in a different amino acid being incorporated into the protein structure. Specifically, this variant involves a change from a thymine (T) to an adenine (A) or cytosine (C) at a precise position on the gene. Because it is located within the coding region of the TPMT gene, researchers study it to determine if it alters the function of the resulting enzyme. Geneticists track such variants to understand how small differences in our DNA sequence can lead to biological diversity between individuals.
The Role of the TPMT Gene
The TPMT gene provides instructions for making an enzyme called thiopurine S-methyltransferase. This enzyme plays a critical role in the body by helping to break down, or metabolize, certain types of medications known as thiopurines. These drugs are often used to treat conditions like leukemia, inflammatory bowel disease, and autoimmune disorders. By converting these drugs into inactive forms, the TPMT enzyme helps regulate the levels of medication in the body, preventing the buildup of toxic byproducts. When the TPMT gene carries certain variants, the activity of this enzyme can be reduced or absent, which may influence how a person responds to these specific medical treatments.
Research Associations and Evidence Strength
Current research into rs9333569 is limited, and its clinical significance is not as well-established as other, more common TPMT variants like *2 or *3A. While some pharmacogenomic studies have identified this variant as a marker in pathways related to stress-response and metabolic processing, the evidence remains preliminary. Unlike well-characterized variants that are routinely used to guide drug dosing, rs9333569 is not currently a standard target for clinical testing. Because the evidence is limited, it is difficult to draw definitive conclusions about how this specific variant affects an individual's health or drug response. Further large-scale studies are required to clarify its functional impact and determine if it holds any predictive value in a clinical setting.
Understanding Your Results
If you have encountered this variant in a genetic report, it is important to understand that having a rare variant does not necessarily mean you will experience a specific health outcome. Genetic associations are often complex and influenced by many other factors, including other genes, lifestyle, and environment. You cannot use this information to diagnose yourself or make changes to your medical treatment. If you are concerned about how your genetics might influence your response to medication, the most important step is to discuss your findings with your clinician or pharmacist. They are trained to interpret genetic data in the context of your overall health history and can provide guidance on whether any specific testing or monitoring is appropriate for your care.
How common is this variant?
The rs9333569 variant is considered rare across global populations according to data from the Genome Aggregation Database (gnomAD).
Frequently asked questions
Is rs9333569 a dangerous mutation?
There is currently no evidence to classify this variant as inherently dangerous. It is a rare genetic change, and its functional impact on the body is not yet fully understood by the scientific community.
Should I get tested for TPMT variants?
Clinical testing for TPMT variants is typically reserved for patients who are about to start specific thiopurine medications. You should consult your doctor to see if such testing is relevant to your specific medical treatment plan.
Does this variant affect my stress levels?
While some research has linked this variant to stress-response pathways, these findings are preliminary. It is not a diagnostic marker for stress or anxiety, and you should not interpret it as such.
Where can I find more information on TPMT?
You can find reliable information on the TPMT gene through resources like MedlinePlus Genetics or the Pharmacogenomics Knowledgebase (PharmGKB). These sites provide educational summaries on how genes influence drug response.
Sources & further reading
Educational information only, last refreshed 9/15/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Defines the TPMT*4 splice-site mutation (c.414+1G>A) causing complete inactivation of thiopurine methyltransferase and severe toxicity.
A rare variant in the TPMT gene associated with metabolic processing.
Defines the non-functional TPMT*2 missense allele (c.238G>C, p.Ala80Pro), which confers significantly impaired thiopurine metabolism and heightened risk of life-threatening myelosuppression with azathioprine or mercaptopurine.
The rs1800460 variant defines the TPMT*3B allele, and in cis with rs1142345, forms the TPMT*3A haplotype conferring deficient thiopurine methyltransferase activity.
The TPMT*3C variant is a major determinant of thiopurine metabolism, associated with reduced enzyme activity.
This missense variant in the TPMT gene is associated with altered thiopurine metabolism and is considered a rare variant in global populations.