CYP2B6 rs72558189: What Your Genotype Means
The rs72558189 variant is a single nucleotide polymorphism located in the CYP2B6 gene, which encodes a key liver enzyme responsible for drug clearance. Carrying the variant allele defines the CYP2B6*5 star allele, which causes a missense amino acid substitution (p.Arg487Cys). Research indicates that this change can influence the clearance and processing of specific medications, including efavirenz, methadone, and bupropion.
What each genotype means
Normal enzyme activity
This genotype corresponds to the wild-type or normal function for this specific variant site. Individuals with this profile typically exhibit standard metabolism for CYP2B6 substrates like efavirenz, methadone, and bupropion. Please discuss any medication dosing or concerns with your clinician or pharmacist.
This is the most common genotype across all major global populations.
Reduced enzyme activity
This genotype includes one copy of the variant allele, which defines the CYP2B6*5 haplotype. Research suggests this may be associated with reduced clearance of certain medications, though the clinical impact can be variable and is often influenced by other co-inherited genetic factors. Please discuss your medication response and dosing with your clinician or pharmacist.
Carried by approximately 2-4% of individuals in many populations, though frequencies vary by ancestry.
Likely reduced enzyme activity
This genotype indicates two copies of the variant allele associated with the CYP2B6*5 haplotype. This may lead to slower metabolism of drugs processed by the CYP2B6 enzyme, potentially increasing the risk of higher drug concentrations in the blood. Please consult with your clinician or pharmacist regarding your specific medication regimen.
This genotype is rare, occurring in less than 1% of most studied populations.
Understanding rs72558189 and the CYP2B6 Gene
The single nucleotide polymorphism rs72558189 is an exonic variant situated within the CYP2B6 gene on chromosome 19. It corresponds to the cDNA change c.1459C>T, which alters codon 487 and results in an arginine-to-cysteine amino acid substitution (p.Arg487Cys). In pharmacogenetic nomenclature cataloged by PharmGKB and the Pharmacogene Variation (PharmVar) Consortium, this specific transition is the core defining variant of the CYP2B6*5 allele. The CYP2B6 gene encodes Cytochrome P450 Family 2 Subfamily B Member 6, an essential phase I hepatic monooxygenase. Although CYP2B6 accounts for a relatively modest percentage of total liver cytochrome P450 content compared to enzymes like CYP3A4, it plays an indispensable role in clearing approximately 4% to 8% of clinically utilized therapeutic compounds. Structural alterations caused by missense variants like p.Arg487Cys can modify the stability or substrate affinity of the enzyme, altering catalytic efficiency.
Pharmacogenetic Associations and Evidence Strength
Pharmacogenetic research has investigated the CYP2B6*5 allele for its effects on the clearance of several therapeutic drugs, most notably the antiretroviral agent efavirenz, the opioid analgesic methadone, and the antidepressant bupropion. When enzyme activity is reduced, drugs cleared primarily by CYP2B6 can linger longer in circulation, potentially elevating systemic drug exposure. However, the evidence strength supporting clinical actionability for rs72558189 specifically is currently considered limited compared to dominant alleles such as CYP2B6*6 (c.516G>T). While some clinical cohorts and in vitro metabolic studies demonstrate diminished metabolic clearance, others report neutral or substrate-specific fluctuations. Because the evidence is mixed and less robust than the data for high-impact CYP2B6 variants, clinical guidelines such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) assess CYP2B6 holistically across all present alleles rather than relying solely on rs72558189.
Ancestry and Population Distribution
The frequency of the rs72558189 variant allele varies across different global populations, though it is generally observed as an uncommon to low-frequency allele. In European and African ancestry cohorts, the minor allele frequency (MAF) typically ranges between 1% and 2%. In East Asian populations, it is even less frequent, with an observed MAF around 0.5%. However, regional multiethnic studies—such as targeted genotyping cohorts in the Middle East—have noted higher localized frequencies in certain sub-populations, highlighting the genetic diversity of the locus. Because the T allele is relatively infrequent in most major continental groups, the vast majority of individuals carry two copies of the common C allele. Homozygous carriers of the alternate T allele remain very rare worldwide.
Clinical Interpretation and Limitations
Finding rs72558189 in a genetic panel provides educational insight into how your liver might process certain compounds, but it cannot diagnose any illness or independently predict drug safety. Pharmacogenetic effects depend heavily on composite diplotypes—meaning rs72558189 must be evaluated alongside other CYP2B6 variants, such as *6 or *18, to determine overall metabolizer status. Furthermore, non-genetic elements such as age, liver function, overall health, co-prescribed medications, and dietary factors exert substantial influence over drug metabolism. Never alter, start, or discontinue any prescription medication based on personal genetic raw data alone. If you take medications metabolized by CYP2B6, share your test findings with a licensed healthcare provider or clinical pharmacogeneticist to determine whether comprehensive dosing considerations are relevant.
How common is this variant?
The minor T allele occurs at a frequency of approximately 1% to 2% in European and African ancestries, while remaining rarer in East Asian populations at roughly 0.5%. The homozygous TT genotype is exceedingly rare across all global populations.
Frequently asked questions
What does having the CYP2B6 rs72558189 variant mean?
Having the variant indicates the presence of the CYP2B6*5 allele, which alters a single amino acid in the CYP2B6 enzyme. This change is associated with modest differences in how the liver clears medications like efavirenz, methadone, and bupropion, though overall evidence remains limited.
Does rs72558189 cause any disease or health symptoms?
No, this genetic variant does not directly cause any disease, disorder, or noticeable physical symptoms on its own. It only becomes biologically relevant when an individual takes specific medications that require the CYP2B6 enzyme for metabolic processing.
How does rs72558189 differ from the common CYP2B6*6 variant?
The rs72558189 variant defines the *5 allele, whereas CYP2B6*6 is defined by a different mutation (c.516G>T, rs3745274). The *6 variant is far more common, has much stronger scientific and clinical evidence, and is the primary driver of dosing adjustments in standard CPIC guidelines.
Should I change my medication dosage if I have this variant?
No, you should never adjust or stop prescription medications based solely on genetic test results. If you are taking drugs like bupropion or efavirenz, consult your physician or pharmacist, who can review your complete health history and diplotype.
Sources & further reading
Educational information only, last refreshed 9/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Defines the non-functional CYP2B6*18 allele (c.983T>C; p.Ile328Thr) leading to impaired metabolism of efavirenz.
Core coding variant c.1459C>T (p.Arg487Cys) defining CYP2B6*5, associated with reduced clearance of substrates.
Key variant defining the CYP2B6*6 reduced-function allele influencing efavirenz, methadone, and bupropion clearance.
Missense alteration defining the CYP2B6*18 allele, causing profound enzymatic deficiency and impaired clearance of efavirenz and methadone.
A coding variant that defines the decreased-function CYP2B6*4 allele, influencing plasma concentrations of efavirenz, methadone, and bupropion.
Missense alteration defining the nonfunctional CYP2B6*18 allele common in African populations that slows clearance of efavirenz.