What you carry at this position in your DNA and what research says about it.
Drug Metabolism: 8/10 evidence, 77 publications.
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Sample genotype (not yours): T/T
Normal Drug Metabolism and Typical Blood Pressure
You carry two functional copies of the CYP3A5 gene, resulting in normal enzyme activity. This allows your body to clear medications like tacrolimus and statins at a typical rate, reducing the risk of certain drug-induced side effects.
What this genotype means: Rapid clearance of tacrolimus and cyclosporine; Typical risk of statin-induced muscle pain; Typical blood pressure regulation.
Sample genotype (not yours): C/C
Slower Drug Metabolism and Elevated Statin Side Effect Risk
You carry two non-functional copies of the CYP3A5 gene, meaning you do not produce active CYP3A5 enzyme. This leads to significantly slower clearance of several common medications, increasing the risk of side effects.
What this genotype means: Slower clearance of tacrolimus and cyclosporine; Increased risk of statin-induced muscle pain; Potential risk of salt-sensitive hypertension.
Sample genotype (not yours): T/C
Intermediate Drug Metabolism
You carry one functional and one non-functional copy of the CYP3A5 gene, resulting in intermediate enzyme activity. Your body processes certain medications slightly slower than normal, which can raise their levels in your blood.
What this genotype means: Intermediate clearance of immunosuppressants; Typical risk of statin-induced muscle pain; Typical blood pressure regulation.
Gene function and biological role
Gene Function: The CYP3A5 gene encodes a member of the cytochrome P450 family of enzymes, which are highly active in the liver, intestines, and kidneys [1]. This enzyme plays a critical role in metabolizing a wide array of therapeutic drugs, including immunosuppressants, statins, and blood thinners [2]. In the kidneys, it is also involved in the breakdown of cortisol, which directly influences how the body regulates sodium and water retention [3]. Genetic variations that reduce or eliminate CYP3A5 activity are extremely common and significantly alter how individuals respond to common medications [4].
Variant Impact: The rs776746 variant, also known as the CYP3A5*3 allele, is a single nucleotide polymorphism that disrupts a splice acceptor site, resulting in a non-functional enzyme [5]. Individuals carrying two copies of this variant allele are classified as CYP3A5 non-expressors, meaning they lack functional CYP3A5 enzyme activity [4]. This lack of activity leads to significantly slower clearance of several medications, increasing the risk of drug toxicity and side effects [2]. Conversely, the variant has also been studied for its evolutionary role in salt retention and blood pressure regulation across different latitudes [6].
Key Insight: Over 85 percent of people of European descent carry two copies of this non-functional variant, making slow metabolism of CYP3A5-targeted drugs the genetic norm in this population.
Location: CYP3A5. Chromosome 7 · 7q22.1 · 99.7 Mb
Origin Story: The functional CYP3A5*1 allele is highly prevalent near the equator, where retaining sodium and water was an evolutionary advantage to prevent dehydration in hot, humid climates. As human populations migrated to cooler, northern latitudes, the non-functional CYP3A5*3 variant became highly favored because reduced salt retention lowered the risk of hypertension in colder environments.
Estimated prevalence by population
Global 14.6%; European 0.5%; African 48.3%; East Asian 7.6%; South Asian 9.0%; Americas 4.9%; Ashkenazi 0.7%; Finnish 0.4%; Middle Eastern 1.1%; Amish 0.4%.
Estimated TT genotype frequency.
Global 25.1%; European 12.8%; African 42.4%; East Asian 40.0%; South Asian 42.0%; Americas 34.4%; Ashkenazi 15.1%; Finnish 12.2%; Middle Eastern 18.9%; Amish 12.5%.
Estimated TC genotype frequency.
Global 60.3%; European 86.7%; African 9.3%; East Asian 52.3%; South Asian 48.9%; Americas 60.8%; Ashkenazi 84.2%; Finnish 87.4%; Middle Eastern 80.0%; Amish 87.1%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Pharmacogenomics
Adverse Drug Reactions
Statin Muscle Pain. Evidence: 6/10. Source: PMID 30595243. Typical Risk.
Immunosuppressant & Biologic Response
Tacrolimus Clearance. Evidence: 8/10. Source: PMID 30801552. Rapid Clearance.
Anticoagulant & Blood Thinner Response
Blood Thinner Clearance. Evidence: 6/10. Source: PMID 36309848. Typical Clearance.
Cardiovascular & Metabolic
Hypertension
Hypertension. Evidence: 3/10. Source: PMID 15492926. Typical Risk.
Showing effects for C/C genotype
Statin Muscle Pain. Evidence: 6/10. Source: PMID 30595243. Increased Risk.
Tacrolimus Clearance. Evidence: 8/10. Source: PMID 30801552. Slow Clearance.
Blood Thinner Clearance. Evidence: 6/10. Source: PMID 36309848. Slower Clearance.
Hypertension. Evidence: 3/10. Source: PMID 15492926. Increased Risk.
Showing effects for T/C genotype
Tacrolimus Clearance. Evidence: 8/10. Source: PMID 30801552. Intermediate.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Carrying two copies of the functional CYP3A5*1 allele means you are a normal expressor of this enzyme [1]. Your liver and kidneys efficiently break down medications that rely on this pathway, such as the immunosuppressant tacrolimus [2]. Because you clear these drugs rapidly, these drugs reach lower levels in you than in those with the non-functional variant [3]. Additionally, your risk of statin-induced muscle pain when taking medications like atorvastatin is typical, as your body processes these drugs efficiently [4]. In terms of cardiovascular health, your genetic profile is associated with typical blood pressure regulation, though some studies suggest a slight predisposition to salt sensitivity depending on dietary intake [5].
Rapid clearance of tacrolimus and cyclosporine; Typical risk of statin-induced muscle pain; Typical blood pressure regulation.
Sample genotype: CC (Homozygous)
Carrying two copies of the non-functional CYP3A5*3 allele makes you a CYP3A5 non-expressor [1]. This genetic profile is highly common in European populations but less frequent in those of African descent [2]. Because you lack active CYP3A5, your body clears medications like tacrolimus, cyclosporine, and certain blood thinners much slower than average [3]. This slow clearance can lead to drug buildup, meaning you may be more sensitive to these medications, with a greater risk of toxicity [4]. Additionally, you have an increased risk of experiencing muscle pain or weakness when taking statins like atorvastatin [5]. Some clinical databases also link this non-functional state to an increased risk of salt-sensitive hypertension, though overall studies show variable effects [6].
Slower clearance of tacrolimus and cyclosporine; Increased risk of statin-induced muscle pain; Potential risk of salt-sensitive hypertension.
Sample genotype: TC (Heterozygous)
Carrying one copy of the non-functional CYP3A5*3 allele makes you an intermediate metabolizer [1]. Your body still produces some active CYP3A5 enzyme, allowing for moderate clearance of drugs like tacrolimus and cyclosporine [2]. While you process these medications slower than normal expressors, you clear them faster than those with two non-functional copies [3]. This intermediate status generally keeps your risk of side effects, such as statin-induced muscle pain, close to typical levels [4]. Your blood pressure regulation and salt sensitivity are also considered typical, with no strongly elevated genetic risks [5].
Intermediate clearance of immunosuppressants; Typical risk of statin-induced muscle pain; Typical blood pressure regulation.
Variants with shared genetic architecture
rs41303343 · CYP3A5 Gene · Chr 7 · Tacrolimus Drug Response
rs10264272 · CYP3A5 Gene · Chr 7 · Drug Metabolism
rs4646450 · CYP3A5 Gene · Chr 7 · Chemotherapy Heart Risk
Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism.
CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults.
The genetic determinants of the CYP3A5 polymorphism.
CYP3A variation and the evolution of salt-sensitivity variants.
Impact of pharmacogenetics on statin-induced myopathy in South-Indian subjects.
Content updated August 2026.
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