What you carry at this position in your DNA and what research says about it.
Tacrolimus Drug Response: 9/10 evidence, 3 publications.
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Sample genotype (not yours): T/T
Normal Tacrolimus Metabolism
This genotype represents normal CYP3A5 enzyme function with no copies of the non-functional *7 variant. Standard doses of tacrolimus are typically cleared rapidly from the body.
What this genotype means: Rapid clearance of tacrolimus; May respond less strongly to immunosuppressants.
Sample genotype (not yours): T/TA
Intermediate Tacrolimus Metabolism
Carrying one copy of the non-functional *7 variant leads to moderately reduced CYP3A5 enzyme activity. Tacrolimus is processed slightly slower than in those with fully functional enzymes.
What this genotype means: Moderately reduced tacrolimus clearance; Intermediate drug metabolism rate.
Sample genotype (not yours): TA/TA
Slow Tacrolimus Metabolism and Higher Toxicity Risk
Carrying two copies of the non-functional *7 variant results in a complete lack of CYP3A5 enzyme activity. This leads to significantly slower clearance of tacrolimus and a higher risk of drug toxicity.
What this genotype means: Significantly slower clearance of tacrolimus; Increased risk of drug-induced kidney toxicity.
Gene function and biological role
Gene Function: The CYP3A5 gene encodes a member of the cytochrome P450 family of enzymes, which are crucial for metabolizing drugs and foreign compounds in the liver and intestines [1]. This enzyme plays a particularly dominant role in clearing immunosuppressive medications used during organ transplantation [2]. Genetic variations in this gene are a primary driver of how quickly or slowly a person processes these drugs [2]. Individuals with fully functional CYP3A5 enzymes are classified as expressors, whereas those carrying non-functional variants are non-expressors [1]. Understanding CYP3A5 genetic status helps clinicians personalize drug dosages to prevent organ rejection or drug-induced toxicity [2].
Variant Impact: The rs41303343 variant is a single-nucleotide insertion in the CYP3A5 gene that defines the CYP3A5*7 star allele [1]. This insertion causes a frameshift mutation, resulting in a premature stop codon and a completely non-functional, truncated protein [1]. Because the resulting enzyme cannot metabolize drugs, individuals carrying this variant have significantly reduced capacity to clear certain medications [2]. This variant is particularly relevant in populations of African descent, where it is found at its highest global frequency [1]. Identifying this variant is essential for optimizing the dosing of narrow-therapeutic-index drugs like tacrolimus [2].
Key Insight: The CYP3A5*7 variant is a frameshift mutation that completely disables the enzyme, making carriers process certain transplant drugs much slower than normal.
Location: CYP3A5. Chromosome 7 · 7q22.1 · 99.7 Mb
Estimated prevalence by population
Global 94.5%; European 99.9%; African 80.8%; East Asian > 99.9%; South Asian 99.9%; Americas 98.1%; Ashkenazi 100.0%; Finnish 100.0%; Middle Eastern 100.0%; Amish 100.0%.
Estimated TT genotype frequency.
Global 5.2%; European 0.1%; African 18.2%; East Asian < 0.1%; South Asian 0.1%; Americas 1.8%; Ashkenazi 0.0%; Finnish 0.0%; Middle Eastern 0.0%; Amish 0.0%.
Estimated TTA genotype frequency.
Global 0.3%; European < 0.1%; African 1.0%; East Asian < 0.1%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi 0.0%; Finnish 0.0%; Middle Eastern 0.0%; Amish 0.0%.
Estimated TATA genotype frequency.
Showing effects for T/T genotype
Pharmacogenomics
Immunosuppressant & Biologic Response
Tacrolimus Clearance. Evidence: 4/10. Source: PMID 30801552. Normal Clearance.
Tacrolimus Toxicity. Evidence: 9/10. Source: PMID 21806386. Typical Risk.
Showing effects for T/TA genotype
Tacrolimus Clearance. Evidence: 4/10. Source: PMID 30801552. Intermediate Clearance.
Showing effects for TA/TA genotype
Tacrolimus Clearance. Evidence: 4/10. Source: PMID 30801552. Slow Clearance.
Tacrolimus Toxicity. Evidence: 9/10. Source: PMID 21806386. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Having two copies of the functional T allele means the CYP3A5 enzyme is produced normally and functions at full capacity [1]. In the context of organ transplantation, individuals with this genotype are rapid or normal metabolizers of the immunosuppressant drug tacrolimus [2]. Because the drug is cleared quickly, standard starting doses may result in blood levels that are too low to prevent organ rejection [2]. Clinicians often use genetic testing to identify normal metabolizers and prescribe higher initial doses of tacrolimus to achieve therapeutic targets rapidly [2]. This genotype is highly common globally, representing the baseline state for the majority of populations [1].
Rapid clearance of tacrolimus; May respond less strongly to immunosuppressants.
Sample genotype: TTA (Heterozygous)
This genotype consists of one functional T allele and one non-functional TA allele, which represents the CYP3A5*7 variant [1]. Having one non-functional copy results in intermediate enzyme activity, meaning drugs like tacrolimus are cleared at a moderate rate [2]. While intermediate metabolizers generally have a lower risk of extreme drug buildup compared to poor metabolizers, they still process medications slower than normal expressors [2]. In clinical settings, monitoring blood drug concentrations remains important to ensure the dose is neither too high nor too low [2]. This intermediate status is most frequently observed in individuals of African ancestry, where the *7 variant is most prevalent [1].
Moderately reduced tacrolimus clearance; Intermediate drug metabolism rate.
Sample genotype: TATA (Homozygous)
Having two copies of the TA allele means both copies of the CYP3A5 gene carry the non-functional *7 mutation, resulting in a complete lack of active enzyme [1]. Individuals with this genotype are classified as poor metabolizers or non-expressors [1]. When treated with standard doses of tacrolimus, they clear the drug very slowly, leading to abnormally high concentrations in the blood [2]. These elevated levels significantly increase the risk of severe side effects, particularly kidney toxicity and dysfunction [2]. To avoid these complications, clinicians typically recommend lower starting doses and intensive blood monitoring for individuals with this genetic profile [2].
Significantly slower clearance of tacrolimus; Increased risk of drug-induced kidney toxicity.
Variants with shared genetic architecture
rs776746 · CYP3A5 Gene · Chr 7 · Drug Metabolism
rs10264272 · CYP3A5 Gene · Chr 7 · Drug Metabolism
rs4646450 · CYP3A5 Gene · Chr 7 · Chemotherapy Heart Risk
Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients.
Content updated August 2026.
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