CYP2D6 rs28371720: Pharmacogenomics and Drug Metabolism
The genetic variant rs28371720 is a single nucleotide polymorphism located within the human CYP2D6 gene on chromosome 22. It is tightly associated with the CYP2D6*41 star allele, a reduced-function haplotype that frequently leads to an intermediate drug metabolizer phenotype. Carrying this variant can influence how quickly or slowly an individual breaks down widely prescribed medications, including antidepressants, opioids, and cardiovascular drugs.
What each genotype means
Normal enzyme activity
This genotype is associated with the presence of two functional copies of the CYP2D6 gene, which typically results in normal metabolism of medications processed by this enzyme. Because CYP2D6 activity can be influenced by other genetic factors and structural variations, please discuss your medication dosing with your clinician or pharmacist.
This is the most common genotype in most global populations.
Reduced enzyme activity
This genotype includes one copy of the reduced-function CYP2D6*41 allele, which may lead to slower metabolism of certain drugs compared to individuals with two fully functional copies. This is often categorized as an intermediate metabolizer phenotype, though clinical impact depends on the specific medication; please consult your healthcare provider regarding your treatment plan.
Carried by approximately 1 in 6 people of European ancestry and is also observed in South Asian populations.
Decreased enzyme activity
This genotype indicates the presence of two copies of the reduced-function CYP2D6*41 allele, which is associated with decreased enzyme activity and potentially slower drug clearance. Individuals with this profile are often classified as intermediate metabolizers, but you should discuss the clinical relevance of this result with your doctor or pharmacist before making any changes to your medications.
This genotype is less common than the heterozygous state, occurring at lower frequencies in European and South Asian populations.
What is rs28371720 and Where Is It Located?
The single nucleotide polymorphism rs28371720 is a variant residing in the cytochrome P450 family 2 subfamily D member 6 (CYP2D6) gene, which maps to chromosome 22q13.2. This genomic region is recognized for high structural diversity and complex homologous pseudogenes. In pharmacogenomics nomenclature, rs28371720 is an informative tag marker for the reduced-function CYP2D6*41 core allele. Rather than causing complete loss of protein function, this haplotype alters enzyme activity levels. Genomic and transcriptomic studies demonstrate that alleles carrying rs28371720 show lowered expression or altered enzymatic activity relative to fully functional reference alleles such as CYP2D6*1. Because CYP2D6 harbors numerous overlapping single nucleotide changes and copy number variations, analyzing rs28371720 provides key haplotype insight when phased with surrounding polymorphisms across the locus.
Biological Function of the CYP2D6 Enzyme
The CYP2D6 enzyme is a pivotal member of the hepatic cytochrome P450 superfamily, responsible for metabolizing an estimated 20% to 25% of clinically used therapeutic drugs. Expressed predominantly in the liver, CYP2D6 processes diverse medication classes, including selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, beta-blockers, antiarrhythmics, and pain medications such as codeine and tramadol. In addition to clearing drugs from circulation through oxidative degradation, the enzyme bioactivates specific prodrugs into their active forms. Depending on inherited genetic variation, individual metabolic capacity ranges widely across four broad phenotypic categories: poor metabolizers, intermediate metabolizers, normal metabolizers, and ultrarapid metabolizers. Genetic variants like rs28371720 down-regulate baseline enzymatic processing capacity, shifting overall diplotype scores toward intermediate activity levels.
Research Associations and Evidence Strength
Clinical pharmacogenetic consortia, including the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG), assign the CYP2D6*41 allele—tagged by rs28371720—a reduced activity score of 0.5 compared to a normal reference score of 1.0. When paired with a non-functional null allele (such as CYP2D6*4), this variant generates an intermediate metabolizer phenotype characterized by impaired drug clearance or diminished prodrug bioactivation. Pharmacogenomic literature indicates that while the association between the *41 allele and decreased hepatic substrate turnover is strongly supported, cataloged evidence specifically isolating rs28371720 alone remains designated as limited. This classification reflects the fact that clinical phenotypes depend on the complete diploid star-allele combination and copy number status rather than an isolated single-site polymorphism.
Population Frequency and Ancestral Distribution
The frequency of rs28371720 and the corresponding CYP2D6*41 star allele varies substantially across worldwide populations. In European cohorts, the minor allele frequency is typically observed at approximately 8% (0.08), establishing it as a primary genetic driver of intermediate metabolizer phenotypes in individuals of European ancestry. In South Asian populations, the minor allele frequency is lower, estimated at approximately 2% (0.02). Broader global sequencing datasets, such as those aggregated in gnomAD and PharmGKB, demonstrate that while present across multiple continental groups, allele distribution is heterogeneous. Because allele frequencies diverge significantly by ancestral background, standard clinical genotyping panels must capture *41 alongside other key ethnic variants (such as *10 in East Asians and *17 in African ancestries) to provide accurate phenotype classification.
Clinical Limitations and What Readers Should Do
Information regarding your rs28371720 genotype cannot independently establish your personal medication dosing, therapeutic drug levels, or clinical safety profile. Drug metabolism is a multifactorial biological process shaped by full CYP2D6 diplotypes, copy number variations (gene deletions or duplications), concomitant drug interactions leading to phenoconversion, organ function, and age. Possessing an allele associated with decreased clearance does not automatically translate to adverse effects or lack of efficacy. You should never alter, stop, or initiate any prescription medication regimen based solely on genetic test results. If your genetic testing report indicates the presence of rs28371720 or a CYP2D6 intermediate metabolizer phenotype, share these findings directly with your physician, clinical geneticist, or pharmacist to interpret the results within clinical prescribing guidelines.
How common is this variant?
The minor allele frequency of rs28371720 is approximately 0.08 in European populations and approximately 0.02 in South Asian cohorts. Across broader global populations, its prevalence varies widely, making it an essential component of standardized multiancestry pharmacogenetic panels.
Frequently asked questions
What does a reduced-function CYP2D6 allele mean for my health?
A reduced-function CYP2D6 allele means your liver produces an enzyme that clears certain drugs more slowly than average. On its own, this variant does not cause disease or illness; it strictly influences how your body processes specific pharmaceutical compounds. Any clinical implications should be evaluated in partnership with a healthcare provider.
Does carrying rs28371720 mean I will experience drug side effects?
No, carrying rs28371720 does not guarantee that you will experience medication side effects or therapeutic failure. Drug response is influenced by overall diplotype combination, kidney and liver health, diet, and co-administered drugs that can inhibit or induce metabolic pathways. It is simply one piece of a complex pharmacological picture.
Can I use this genetic test result to change my medication dose?
No, you should never adjust, discontinue, or start any medication based on raw genetic data. Only a licensed clinician or clinical pharmacist can determine appropriate drug choice and dosage using established clinical guidelines. Always bring your pharmacogenetic report to your doctor for professional review.
Why is rs28371720 linked to the CYP2D6*41 star allele?
In pharmacogenomics, specific combinations of variants that are inherited together are organized into star-allele haplotypes. The rs28371720 variant serves as a recognized tag marker for the CYP2D6*41 core allele, which causes decreased enzymatic function. Phasing this marker with other nearby variants allows laboratory software to assign your functional star allele correctly.
Sources & further reading
Educational information only, last refreshed 9/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP2D6
This variant is a key marker for the CYP2D6*10 allele, which results in reduced enzymatic activity and altered metabolism of various psychiatric and analgesic medications.
This variant defines the CYP2D6*4 non-functional allele, which causes impaired metabolism of numerous clinically prescribed medications including antidepressants, tamoxifen, and codeine.
Defines the CYP2D6*17 allele (p.Thr107Ile), which exhibits reduced enzyme activity towards substrates like codeine and certain antidepressants.
Defines the CYP2D6*29 variant (p.Val338Met) conferring decreased metabolic capacity, primarily observed in populations of African descent.
Promoter variant defining the CYP2D6*41 allele, associated with reduced enzyme expression and decreased metabolic capacity for various drugs.
Defines the non-functional CYP2D6*41 splice defect associated with intermediate metabolizer phenotype affecting codeine, tamoxifen, and SSRI metabolism.