CYP2B6 rs4986895: What Your Genotype Means
The rs4986895 single-nucleotide polymorphism is a missense coding variant located within the human CYP2B6 gene on chromosome 19. It defines the CYP2B6*4 star allele, which has been investigated for altered clearance and metabolism of therapeutic compounds such as efavirenz, methadone, and bupropion. Current pharmacogenomic research rates the overall clinical evidence for this variant alone as limited, with observed functional effects often depending heavily on substrate context and complex haplotypes.
What each genotype means
| Genotype | What the research suggests | Reading |
|---|---|---|
| AA | This homozygous reference genotype represents two baseline alleles at this locus, typically associated with standard CYP2B6 enzyme expression. Individuals with this genotype do not carry the specific amino acid alteration defining the isolated *4 variant on either chromosome. In the absence of other CYP2B6 alterations, this profile is consistent with standard baseline drug metabolism capacity. | Informational |
| AG | This heterozygous genotype indicates the presence of one baseline allele and one variant allele at rs4986895. In pharmacogenomic nomenclature, it is often evaluated to assess whether the patient carries an isolated CYP2B6*4 allele or a complex haplotype like CYP2B6*6. The overall impact on substrate clearance is variable, substrate-dependent, and considered to have limited standalone clinical weight. | Informational |
| GG | This homozygous variant genotype indicates that two copies of the rs4986895 alternative allele are present. While in vitro systems and clinical cohorts note altered hepatic expression and altered metabolism for drugs like efavirenz or methadone, clinical guidelines do not currently establish independent dosing modifications for this marker alone. Individuals carrying this genotype should rely on full pharmacogenetic panel assessments rather than single-SNP analysis. | Higher attention |
Genetic Architecture and Molecular Profile
The single-nucleotide polymorphism rs4986895 is situated within exon 5 of the cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene on chromosome 19q13.2. At the DNA sequence level, this variant represents a single base transition that leads to an amino acid substitution in the mature enzyme. When occurring as an isolated variation, it is designated in standard pharmacogenomic star-allele nomenclature as the CYP2B6*4 allele. The CYP2B6 locus is recognized across genomic databases as one of the most polymorphic and structurally diverse cytochrome P450 genes in humans. Importantly, this same missense change frequently appears alongside other coding variations—most notably rs3745274 (c.516G>T)—to form the widespread, clinically significant CYP2B6*6 composite haplotype. Distinguishing whether rs4986895 exists on its own as *4 or as a component of *6 requires phased haplotyping, which is critical for accurate molecular profiling.
Biological Role of the CYP2B6 Enzyme
The CYP2B6 gene encodes a membrane-bound, microsomal monooxygenase belonging to the cytochrome P450 superfamily. Primarily synthesized in hepatocytes within the liver, the enzyme is responsible for the phase I oxidative clearance, hydroxylation, and bioactivation of numerous endogenous lipids and clinical drugs. CYP2B6 metabolizes a diverse spectrum of pharmaceutical agents, including the non-nucleoside reverse transcriptase inhibitor efavirenz, the opioid maintenance therapy methadone, the antidepressant bupropion, and the chemotherapeutic agent cyclophosphamide. Because of this enzyme's pivotal role in clearing bioactive drugs, variations in protein structure or baseline expression can modify steady-state plasma concentrations in the bloodstream. Consequently, changes in catalytic capacity may shift the delicate balance between therapeutic efficacy, subtherapeutic clearance, and potential toxicity for its substrates.
Current Research and Clinical Evidence
Scientific investigations cataloged in PharmGKB, PubMed, and clinical pharmacogenomics consortia note that the isolated CYP2B6*4 allele defined by rs4986895 demonstrates subtle and substrate-dependent properties. In vitro expression studies have reported altered protein expression and variable catalytic activity depending on the medication tested. In clinical cohorts examining the antiretroviral efavirenz, the opioid methadone, and the smoking-cessation drug bupropion, individuals carrying this allele have shown altered plasma drug concentrations. However, major pharmacogenomic bodies, including the Clinical Pharmacogenetics Implementation Consortium (CPIC), regard the clinical impact of isolated *4 as having limited or insufficient evidence to warrant actionable dose modifications on its own. Much of the measurable metabolic variability observed in early studies is attributable to the closely linked CYP2B6*6 haplotype rather than the standalone rs4986895 substitution.
Global Allele Frequencies and Ancestry
The minor allele of rs4986895 occurs at relatively low to moderate frequencies globally when evaluated across multi-ethnic sequencing projects such as the 1000 Genomes Project and gnomAD. According to population data compiled across genomic resources, the minor allele frequency is approximately 0.04 in individuals of African ancestry and roughly 0.03 in populations of European descent. In various Asian sub-populations, the allele has been observed at frequencies ranging from 0.05 up to 0.12 in selective study cohorts. Because the base change is frequently co-inherited in linkage disequilibrium with other CYP2B6 polymorphisms, population distributions can vary substantially when isolating the unlinked *4 allele versus larger haplotype networks.
Navigating Personal Results and Next Steps
Learning that you carry one or two copies of rs4986895 provides personal genetic insight, but it cannot be used in isolation to diagnose illness or predict definitive drug reactions. Enzymatic activity in vivo is dictated not just by a single DNA base, but by full-gene haplotypes, co-prescribed medications that inhibit or induce cytochrome P450 enzymes, kidney and liver health, diet, and age. For these reasons, you must never start, stop, or adjust the dosage of any prescribed medication based on this genetic finding alone. If you take or plan to take CYP2B6-metabolized medications such as efavirenz, methadone, or bupropion, discuss your comprehensive pharmacogenomic results with a licensed physician or pharmacist.
How common is this variant?
The minor allele frequency for rs4986895 is approximately 0.04 in African populations and around 0.03 in European populations, with moderate frequencies reported across Asian cohorts.
Frequently asked questions
What is the difference between CYP2B6*4 and CYP2B6*6?
The rs4986895 variant defines the CYP2B6*4 allele when it appears alone. However, when rs4986895 is co-inherited on the same chromosome alongside another specific variant (rs3745274), the combination forms the far more common and significantly reduced-function CYP2B6*6 haplotype.
Does having the rs4986895 variant mean my medications will not work?
No, possessing this variant does not mean your medications will fail. The evidence linking isolated rs4986895 to altered clinical response is classified as limited, and overall drug response is influenced by multiple genes, drug interactions, and lifestyle factors.
Which drugs are processed by the CYP2B6 enzyme?
The CYP2B6 enzyme metabolizes a broad range of therapeutics, most prominently the antiretroviral medication efavirenz, the opioid methadone, the antidepressant bupropion, and the chemotherapeutic cyclophosphamide.
Should I alter my medication dose if I carry this variant?
No, you should never modify your prescription medication dose on your own. Major clinical bodies like CPIC do not recommend dosing adjustments based solely on isolated rs4986895 status; consult your doctor or pharmacist to interpret your results in full clinical context.
Sources & further reading
Educational information only, last refreshed 9/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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