What you carry at this position in your DNA and what research says about it.
Medication Clearance Rate: 7/10 evidence, 30 publications.
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Sample genotype (not yours): G/G
Typical Medication Clearance Rate
Standard CYP3A4 enzyme activity allows for normal breakdown of many common medications. Standard dosing is typically appropriate for drugs like tacrolimus, cyclosporine, and statins.
What this genotype means: Typical rate of drug metabolism; Typical response to statins and immunosuppressants; Lower risk of drug accumulation and toxicity.
Sample genotype (not yours): A/A
Significantly Slower Medication Clearance
Highly reduced CYP3A4 enzyme activity slows the breakdown of many common medications, which is associated with a greater chance of side effects. CYP3A4 is one of the genes clinicians consider when prescribing drugs that depend on it.
What this genotype means: Significantly slower metabolism of many common medications; High risk of drug toxicity and side effects; Substantially greater sensitivity to drugs like tacrolimus and cyclosporine.
Sample genotype (not yours): G/A
Slower Medication Clearance Rate
Reduced CYP3A4 enzyme activity slows the breakdown of several common medications, increasing the risk of side effects. Greater sensitivity to drugs like tacrolimus, cyclosporine and statins.
What this genotype means: Slower metabolism of many common medications; Increased risk of side effects from statins and immunosuppressants; Greater sensitivity to drugs like tacrolimus and cyclosporine.
Gene function and biological role
Gene Function: The CYP3A4 gene encodes cytochrome P450 3A4, one of the most important drug-metabolizing enzymes in the human body. This enzyme is highly active in the liver and intestines, where it processes an estimated 30 percent to 50 percent of all clinically prescribed medications [1]. It plays a critical role in clearing immunosuppressants, cholesterol-lowering statins, chemotherapy agents, and many psychiatric drugs [2]. Widespread genetic variation in this gene contributes to significant differences in how quickly individuals metabolize these substances [3]. Understanding these genetic differences helps clinicians personalize drug selection and dosing to improve efficacy and minimize side effects [4].
Variant Impact: The rs35599367 variant, also known as the CYP3A4*22 allele, is an intronic single nucleotide polymorphism located in intron 6 of the CYP3A4 gene [1]. This genetic change alters the normal splicing of the gene's messenger RNA, causing partial retention of intron 6 [1]. This splicing defect leads to a twofold or greater increase in the formation of a nonfunctional alternative splice variant in the liver [1]. Consequently, individuals carrying the minor A allele have significantly reduced levels of functional CYP3A4 protein and lower overall enzyme activity [2]. This reduction in activity slows down the clearance of many CYP3A4 substrate drugs, leading to higher blood concentrations and an increased risk of adverse drug reactions [3].
Key Insight: The CYP3A4*22 variant does not change the protein sequence directly; instead, it acts like a genetic glitch during RNA splicing, causing the liver to produce a nonfunctional version of the enzyme.
Location: CYP3A4. Chromosome 7 · 7q22.1 · 99.8 Mb
Estimated prevalence by population
Global 93.8%; European 90.4%; African 98.2%; East Asian 100.0%; South Asian 98.2%; Americas 95.0%; Ashkenazi 88.7%; Finnish 93.0%; Middle Eastern 96.6%; Amish 89.5%.
Estimated GG genotype frequency.
Global 6.1%; European 9.4%; African 1.7%; East Asian 0.0%; South Asian 1.8%; Americas 5.0%; Ashkenazi 11.0%; Finnish 6.8%; Middle Eastern 3.3%; Amish 10.2%.
Estimated GA genotype frequency.
Global 0.1%; European 0.2%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas 0.1%; Ashkenazi 0.3%; Finnish 0.1%; Middle Eastern < 0.1%; Amish 0.3%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Pharmacogenomics
Immunosuppressant & Biologic Response
Tacrolimus Clearance. Evidence: 7/10. Source: PMID 29160300. Typical Clearance.
Cyclosporine Clearance. Evidence: 6/10. Source: PMID 21902502. Typical Clearance.
Lipid-Lowering Drug Response
Evidence: 3/10. Source: PMID 20386561. Typical Sensitivity.
Antimicrobial & Antiviral Response
Erythromycin Clearance. Evidence: 5/10. Source: PMID 23327575. Typical Clearance.
Anesthesia Response
Alprazolam Clearance. Evidence: 5/10. Source: PMID 32112986. Typical Clearance.
Showing effects for A/A genotype
Tacrolimus Clearance. Evidence: 7/10. Source: PMID 29160300. Slower Clearance.
Cyclosporine Clearance. Evidence: 6/10. Source: PMID 21902502. Slower Clearance.
Evidence: 3/10. Source: PMID 20386561. Higher Sensitivity.
Erythromycin Clearance. Evidence: 5/10. Source: PMID 23327575. Slower Clearance.
Alprazolam Clearance. Evidence: 5/10. Source: PMID 32112986. Slower Clearance.
Showing effects for G/A genotype
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Typical CYP3A4 enzyme activity characterizes this common genetic profile [1]. Standard clearance rates allow for normal breakdown of a wide range of medications [1]. For immunosuppressants like tacrolimus and cyclosporine, standard clinical dosing protocols are usually effective [2]. Similarly, standard doses of cholesterol-lowering statins, such as simvastatin and atorvastatin, are typically well-tolerated and effective [3]. However, because metabolism is rapid compared to carriers of the variant allele, certain medications may sometimes reach lower levels [2]. It is important to note that other genetic and lifestyle factors, such as diet and other enzymes, also influence overall drug clearance.
Typical rate of drug metabolism; Typical response to statins and immunosuppressants; Lower risk of drug accumulation and toxicity.
Sample genotype: AA (Homozygous)
The lowest levels of functional CYP3A4 enzyme activity occur in those with two copies of the A allele [1]. This genetic profile causes a substantial portion of the enzyme to be produced as a nonfunctional splice variant [2]. Consequently, the clearance of many widely used medications is severely reduced, which can lead to drug accumulation and toxicity [3]. Patients taking immunosuppressants like tacrolimus or cyclosporine are typically much more sensitive to them than average [4]. Slower clearance also significantly elevates the risk of adverse events, including kidney damage, delayed graft function, and drug toxicity [5]. Similarly, cholesterol-lowering statins must often be prescribed at much lower doses to avoid muscle pain and other side effects [6].
Significantly slower metabolism of many common medications; High risk of drug toxicity and side effects; Substantially greater sensitivity to drugs like tacrolimus and cyclosporine.
Sample genotype: GA (Heterozygous)
A significant reduction in CYP3A4 enzyme activity is associated with the presence of one A allele [1]. This reduction occurs because the variant alters RNA splicing, leading to a nonfunctional splice variant [2]. As a result, many medications metabolized by this enzyme clear from the body more slowly, potentially leading to higher drug levels in the blood [3]. For transplant recipients, this slower clearance means tacrolimus or cyclosporine build up more readily, with a greater toxicity risk [4]. Slower metabolism also increases the risk of side effects from statins, because the drug reaches higher levels [5]. Additionally, standard doses of other drugs, such as erythromycin or alprazolam, may cause heightened side effects or toxicity [6].
Slower metabolism of many common medications; Increased risk of side effects from statins and immunosuppressants; Greater sensitivity to drugs like tacrolimus and cyclosporine.
Variants with shared genetic architecture
rs2242480 · CYP3A4 Gene · Chr 7 · Drug Metabolism and Heart Risk
rs2740574 · CYP3A4 Gene · Chr 7 · Prostate Cancer Risk
rs4646437 · CYP3A4 Gene · Chr 7 · Drug Metabolism and Health
CYP3A4 intronic SNP rs35599367 (CYP3A4*22) alters RNA splicing.
CYP3A4*22: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy.
Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs.
Content updated August 2026.
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