What you carry at this position in your DNA and what research says about it.
Drug Metabolism and Health: 5/10 evidence, 20 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): G/G
Typical Drug Metabolism and Standard Health Risks
Standard enzyme activity levels process most medications at a typical rate. There is a baseline risk for conditions like lung cancer and hypertension.
What this genotype means: Standard clearance rates for most medications; Typical baseline risk for lung cancer and hypertension.
Sample genotype (not yours): A/A
Faster Drug Clearance and Mixed Health Risks
Two copies of the A allele significantly accelerate the metabolism of certain medications while altering others. This genotype offers protection against lung cancer but increases hypertension risk.
What this genotype means: Significantly lower risk of non-small cell lung cancer; Increased risk of hypertension; Faster clearance of tacrolimus, with lower blood levels.
Sample genotype (not yours): G/A
Altered Drug Clearance and Mixed Health Risks
One copy of the A allele alters the processing speed of several medications. This genotype is linked to a lower risk of lung cancer but a higher risk of hypertension.
What this genotype means: Lower risk of non-small cell lung cancer; Increased risk of high blood pressure; Altered sensitivity to specific prescription drugs.
Gene function and biological role
Gene Function: CYP3A4 encodes cytochrome P450 3A4, one of the most important drug-metabolizing enzymes in the human body. Located primarily in the liver and intestines, this enzyme is responsible for processing over half of all clinically prescribed medications [1]. It plays a critical role in clearing toxins, hormones, and foreign compounds from the system [2]. Variations in this gene can significantly alter how rapidly a person processes specific drugs, leading to differences in medication efficacy and side effect risks [3].
Variant Impact: The rs4646437 variant is an intron change located within the CYP3A4 gene. This genetic variation influences the expression levels and overall catalytic activity of the CYP3A4 enzyme in the liver [2]. The minor A allele is associated with altered metabolic rates for several therapeutic drugs, including immunosuppressants and chemotherapies [4]. Beyond drug processing, this variant has been linked to differences in susceptibility to certain cancers and cardiovascular conditions [5].
Key Insight: This single genetic marker influences both how your liver processes common prescription medications and your baseline susceptibility to certain cancers and high blood pressure.
Location: CYP3A4. Chromosome 7 · 7q22.1 · 99.8 Mb
Estimated prevalence by population
Global 57.2%; European 79.9%; African 8.0%; East Asian 72.1%; South Asian 41.3%; Americas 65.1%; Ashkenazi 78.3%; Finnish 83.2%; Middle Eastern 59.6%; Amish 86.2%.
Estimated GG genotype frequency.
Global 27.1%; European 19.0%; African 40.6%; East Asian 25.6%; South Asian 45.9%; Americas 31.2%; Ashkenazi 20.4%; Finnish 16.1%; Middle Eastern 35.2%; Amish 13.3%.
Estimated GA genotype frequency.
Global 15.6%; European 1.1%; African 51.3%; East Asian 2.3%; South Asian 12.8%; Americas 3.7%; Ashkenazi 1.3%; Finnish 0.8%; Middle Eastern 5.2%; Amish 0.5%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 3/10. Source: PMID 32464168. Typical Risk.
Cardiovascular & Metabolic
Hypertension
Hypertension. Evidence: 5/10. Source: PMID 26810136. Typical Risk.
Pharmacogenomics
Chemotherapy Response
Chemotherapy Response. Evidence: 5/10. Source: PMID 25829401. Typical Response.
Neurology & Mental Health
Addiction & Reward
Addiction Risk. Evidence: 3/10. Source: PMID 31799230. Typical Risk.
Showing effects for A/A genotype
Lung Cancer. Evidence: 3/10. Source: PMID 32464168. Significantly Lower.
Hypertension. Evidence: 5/10. Source: PMID 26810136. Increased Risk.
Chemotherapy Response. Evidence: 5/10. Source: PMID 25829401. Stronger Response.
Addiction Risk. Evidence: 3/10. Source: PMID 31799230. Lower Risk.
Showing effects for G/A genotype
Lung Cancer. Evidence: 3/10. Source: PMID 32464168. Lower Risk.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Standard enzyme activity is maintained with this genotype, resulting in typical clearance rates for many common medications [1]. When taking the immunosuppressant tacrolimus, this genotype is associated with slower drug clearance, which can lead to higher blood concentrations and requires careful monitoring [2]. Similarly, cyclosporine is metabolized more slowly, which may sometimes result in a better therapeutic response but also increases the risk of side effects [3]. Standard baseline risks are observed for non-small cell lung cancer and drug addiction [4] [5]. There is no elevated risk of sunitinib-induced hypertension or chemotherapy-related adverse events [6].
Standard clearance rates for most medications; Typical baseline risk for lung cancer and hypertension.
Sample genotype: AA (Homozygous)
Accelerated clearance of the immunosuppressant tacrolimus is common with this genotype, so blood levels can fall below the range needed to prevent transplant rejection [1]. Slower metabolism of other substances like methadone can lead to more severe side effects [2]. On the clinical front, chemotherapy treatments with cisplatin or doxorubicin show higher survival rates and better overall outcomes [3]. General health profiles show a highly protective effect against non-small cell lung cancer and a lower susceptibility to drug addiction [4] [5]. However, this is accompanied by an elevated risk of developing high blood pressure, especially during sunitinib therapy [6].
Significantly lower risk of non-small cell lung cancer; Increased risk of hypertension; Faster clearance of tacrolimus, with lower blood levels.
Sample genotype: GA (Heterozygous)
Enzyme activity is altered by the presence of one A allele, affecting how various medications are processed in the liver [1]. Slower clearance of drugs like voriconazole and methadone can increase the risk of experiencing adverse side effects [2] [3]. Conversely, a better response and increased survival rates have been observed during chemotherapy treatments with cisplatin or doxorubicin [4]. In terms of general health, a significantly lower risk of developing non-small cell lung cancer has been documented [5]. However, there is an increased likelihood of developing high blood pressure, particularly when treated with certain cancer therapies like sunitinib [6].
Lower risk of non-small cell lung cancer; Increased risk of high blood pressure; Altered sensitivity to specific prescription drugs.
Variants with shared genetic architecture
rs2242480 · CYP3A4 Gene · Chr 7 · Drug Metabolism and Heart Risk
rs35599367 · CYP3A4 Gene · Chr 7 · Medication Clearance Rate
rs2740574 · CYP3A4 Gene · Chr 7 · Prostate Cancer Risk
Sex-dependent genetic markers of CYP3A4 expression and activity in human liver microsomes.
Effects of CYP3A4 Polymorphisms on Drug Addiction Risk Among the Chinese Han Population.
Effects of CYP3A4 polymorphisms on the plasma concentration of voriconazole.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com