CYP3A5 rs7767463: What Your Genotype Means for Tacrolimus
The rs7767463 variant is a well-studied genetic marker located within the CYP3A5 gene. It is primarily associated with the body's ability to metabolize the immunosuppressant medication tacrolimus, which is commonly used in solid-organ transplant recipients.
What each genotype means
Extensive enzyme activity
This genotype is associated with the functional CYP3A5*1 allele, which leads to the production of active CYP3A5 enzyme. Individuals with this profile are often classified as extensive metabolizers of tacrolimus, which may result in faster drug clearance and lower blood trough levels. Please discuss your tacrolimus dosing requirements with your transplant clinician or pharmacist.
This genotype is most common in individuals of African ancestry and is relatively rare in populations of European descent.
Intermediate enzyme activity
This genotype indicates you carry one functional CYP3A5*1 allele and one non-functional CYP3A5*3 allele. You are likely an intermediate metabolizer of tacrolimus, which may influence how quickly your body processes the medication compared to those who do not express the enzyme. Please consult your healthcare provider or pharmacist regarding your specific tacrolimus dosing strategy.
This genotype is frequently observed in individuals of African ancestry and is found in a smaller percentage of individuals of European ancestry.
Reduced enzyme activity
This genotype represents two copies of the non-functional CYP3A5*3 allele, often referred to as a poor metabolizer phenotype. Because you do not produce functional CYP3A5 enzyme, your body may clear tacrolimus more slowly, potentially leading to higher blood concentrations. Always discuss your medication dosing and monitoring with your transplant team or pharmacist.
This is the most common genotype in individuals of European ancestry, occurring in the vast majority of that population.
What is the rs7767463 Variant?
The rs7767463 variant, often referred to in clinical literature as the CYP3A5*3 allele, is a single nucleotide polymorphism (SNP) located within the CYP3A5 gene. Specifically, this variant involves an intronic transition that creates a cryptic splice site. This alteration leads to the production of a non-functional protein, effectively preventing the expression of the CYP3A5 enzyme in individuals who carry two copies of the variant. Because this enzyme is responsible for breaking down various substances in the body, including specific medications, the presence or absence of this functional protein can significantly change how a person processes drugs. It is one of the most frequently studied variants in the field of pharmacogenomics due to its clear impact on enzyme activity.
The Role of the CYP3A5 Gene
The CYP3A5 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily found in the liver and intestines, where they play a critical role in the metabolism of a wide range of endogenous compounds and exogenous substances, such as medications. In the context of clinical medicine, CYP3A5 is a major enzyme involved in the metabolism of tacrolimus, a drug used to prevent organ rejection in transplant patients. Individuals who possess at least one functional copy of the gene are considered 'expressers' and can metabolize tacrolimus more rapidly. Conversely, those who lack functional copies are 'non-expressers' and may clear the drug from their system more slowly, which can lead to higher blood concentrations of the medication if standard doses are used.
Research and Clinical Associations
Research consistently demonstrates that the rs7767463 variant is a significant predictor of tacrolimus pharmacokinetics. Numerous studies have shown that patients who are non-expressers (homozygous for the variant) require lower doses of tacrolimus to achieve therapeutic blood levels compared to those who express the enzyme. The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides guidelines based on this genotype to help clinicians adjust dosing to avoid toxicity or sub-therapeutic levels. While the evidence linking this variant to tacrolimus metabolism is strong, it is important to note that other factors, such as drug-drug interactions, liver function, and other genetic variants, also influence how a patient responds to medication. This variant is a tool for personalized medicine, but it is not the sole determinant of clinical outcomes.
Understanding Your Results
If you have received information about your rs7767463 genotype, it is essential to understand that this information is intended for educational purposes and should not be used to make independent medical decisions. Genetic testing for this variant is typically performed in a clinical setting for patients who are about to undergo or have undergone an organ transplant. If you are currently taking tacrolimus or are scheduled for a transplant, you must discuss your genetic status with your transplant team, physician, or clinical pharmacist. They are the only ones qualified to interpret these results in the context of your overall health, current medications, and clinical needs. Never change your medication dosage or stop taking a prescribed drug based on genetic information without direct guidance from your healthcare provider.
How common is this variant?
The frequency of the non-functional allele is approximately 90% in European populations, while it ranges from 24% to 32% in other global populations.
Frequently asked questions
What does it mean to be a CYP3A5 non-expresser?
Being a non-expresser means your body does not produce the functional CYP3A5 enzyme due to your genetic makeup. This can lead to slower metabolism of certain medications, such as tacrolimus, which may require your doctor to adjust your dosage.
Does this variant affect all medications?
No, this variant specifically affects the metabolism of drugs processed by the CYP3A5 enzyme, such as tacrolimus. It does not necessarily affect how your body processes other types of medications.
Should I get tested for rs7767463?
Genetic testing for this variant is usually ordered by transplant specialists when a patient is prescribed tacrolimus. You should discuss the necessity of this test with your healthcare provider based on your specific medical situation.
Can I change my tacrolimus dose based on my genotype?
Absolutely not. Any adjustments to your medication dosage must be made exclusively by your transplant team or physician, as they must balance your genetic profile with your blood test results and clinical condition.
Sources & further reading
Educational information only, last refreshed 10/26/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP3A5
This SNP influences the expression levels of the CYP3A5 enzyme, impacting the clearance rates of tacrolimus.
Defines the CYP3A5*3 splice-altering variant (c.6986A>G) that leads to absent CYP3A5 activity and dictates dosing requirements for the immunosuppressant tacrolimus.