CYP2D6 rs72558186: Understanding the *14B Allele
The rs72558186 variant is a specific genetic change within the CYP2D6 gene that defines the *14B allele. This variant is associated with reduced or abolished activity of the CYP2D6 enzyme, which plays a critical role in how the body processes many common medications.
What each genotype means
Typical enzyme function
You carry two reference copies of the CYP2D6 gene at this position, lacking the specific variant defining the CYP2D6*14B allele. While this indicates normal baseline function at this specific site, overall CYP2D6 activity depends on your broader diplotype across other variants. Always consult a healthcare professional or pharmacist before making any decisions regarding CYP2D6-metabolized medications.
Carried by more than 98% of individuals across world populations, including the vast majority of European and East Asian cohorts.
Decreased enzyme metabolism
You carry one altered G allele associated with the loss-of-function CYP2D6*14B allele (c.506A>G, p.His169Arg). In pharmacogenomic research, carrying one non-functional copy can reduce overall clearance of certain substrate medications depending on the paired allele on your other chromosome. Discuss any medication dosing or therapy choices with your physician or pharmacist.
Found in approximately 1% to 2% of East Asian populations and is very rare (<0.5%) in most other global ancestries.
Markedly reduced metabolism
You carry two altered G alleles, indicating homozygous inheritance of the CYP2D6*14B defining core variant. Published studies associate this status with abolished or severely reduced CYP2D6 enzymatic activity, which can alter drug activation or clearance for numerous prescription medications. You should review your personalized medication plan and dosage with a doctor or clinical pharmacist.
Extremely rare globally, occurring in fewer than 1 in 10,000 individuals, but slightly more detectable in individuals of East Asian ancestry.
What is rs72558186?
The rs72558186 variant is a single-nucleotide polymorphism (SNP) located within the CYP2D6 gene. In the context of pharmacogenomics, this specific change is recognized as the defining missense mutation for the CYP2D6*14B allele. Scientifically, this is often referred to as c.506A>G, which results in an amino acid substitution known as p.His169Arg. Because the CYP2D6 gene is highly polymorphic—meaning it contains many different variations—researchers use a 'star allele' nomenclature system to categorize these changes. The *14B allele is one of many variations that can alter the structure and function of the resulting protein. By identifying this specific SNP, researchers can better understand how an individual's genetic makeup might influence their body's ability to break down or activate certain chemical compounds, including therapeutic drugs.
The Role of the CYP2D6 Gene
The CYP2D6 gene provides instructions for making an enzyme called cytochrome P450 2D6. This enzyme is primarily produced in the liver and is responsible for metabolizing approximately 20% of all clinically used drugs. These medications span a wide range of medical fields, including psychiatry, pain management, cardiology, and oncology. The enzyme works by chemically modifying these drugs, which can either deactivate them for excretion or convert them into their active forms. Because the gene is so diverse, individuals can have different versions of the enzyme that function at varying speeds. Some people are 'extensive' or 'normal' metabolizers, while others may be 'poor' or 'intermediate' metabolizers due to variants like rs72558186. Understanding these differences is a cornerstone of pharmacogenomics, as it helps explain why people may experience different side effects or varying levels of drug efficacy when taking the same medication at the same dose.
Research and Clinical Evidence
Research into rs72558186 and the *14B allele indicates that this variant is associated with reduced or abolished substrate clearance. This means that the enzyme produced by this version of the gene may not process drugs as efficiently as the standard version. However, the evidence strength for this specific variant is currently classified as limited. While it is known to contribute to the loss-of-function profile of the *14B allele, the clinical impact of this variant on specific drug therapies is still being studied. Pharmacogenomic guidelines often focus on 'Tier 1' alleles with well-established clinical significance, while variants like rs72558186 are often categorized as having moderate or emerging effects. Because the field of pharmacogenomics is rapidly evolving, clinicians rely on comprehensive testing panels to interpret how these variants interact with other genetic factors to predict an individual's overall metabolic phenotype.
What This Means for You
If you have received information about your CYP2D6 genotype, it is important to remember that genetic testing is only one piece of the puzzle. The presence of the rs72558186 variant does not automatically mean you will experience a specific health outcome or drug reaction. Many factors, including your age, liver health, diet, and other medications you may be taking, also influence how your body processes drugs. You should never use genetic information to make decisions about your medication, such as changing your dose or stopping a treatment, without consulting your healthcare provider. If you are concerned about how your genetics might affect your response to a prescription, bring your report to your doctor or a clinical pharmacist. They are the best resources to help you interpret these results in the context of your personal medical history and current treatment plan.
How common is this variant?
The rs72558186 variant has a minor allele frequency (MAF) of less than 0.005 globally, though it is notably enriched in East Asian populations, where frequencies typically range from 0.01 to 0.02.
Frequently asked questions
What is the CYP2D6 gene?
The CYP2D6 gene encodes an enzyme in the liver that is responsible for breaking down about one-fifth of all commonly prescribed medications. It is highly variable, meaning many people have different versions of this gene that affect how quickly they process drugs.
Does having the rs72558186 variant mean I am a poor metabolizer?
The rs72558186 variant is associated with reduced enzyme function, but your overall metabolizer status depends on your entire diplotype, which includes both copies of your CYP2D6 gene. A clinician must look at the full picture to determine if you are a poor, intermediate, or normal metabolizer.
Should I get tested for CYP2D6 variants?
Pharmacogenomic testing is generally recommended only when a patient is prescribed a medication known to be processed by the CYP2D6 enzyme. You should discuss the necessity of such testing with your doctor based on your specific medical needs.
Can I change my CYP2D6 genotype?
No, your genotype is inherited from your parents and remains the same throughout your life. While you cannot change your genes, knowing your genotype can help your doctor choose the most appropriate medication and dosage for you.
Sources & further reading
Educational information only, last refreshed 10/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.