What you carry at this position in your DNA and what research says about it.
Medication Metabolism: 5/10 evidence, 11 publications.
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Sample genotype (not yours): A/A
Altered Beta-Blocker Response
Carrying two copies of the A allele is associated with an increased risk of a slow heart rate when using certain beta-blockers like timolol. Other medications like clozapine are processed normally.
What this genotype means: Increased risk of slow heart rate from timolol eye drops; Typical clozapine metabolism and clearance.
Sample genotype (not yours): A/G
Carrying one copy of the G allele and one copy of the A allele is linked to an increased risk of a slow heart rate from beta-blockers like timolol.
What this genotype means: Increased risk of slow heart rate from timolol eye drops; Typical clozapine metabolism.
Sample genotype (not yours): G/G
Slower Clozapine Metabolism
Carrying two copies of the G allele is associated with slower metabolism of clozapine and a higher risk of adverse reactions, while beta-blocker response is typical.
What this genotype means: Slower clozapine metabolism and higher side-effect risk; May respond less strongly to dexmedetomidine; Typical response to timolol beta-blockers.
Gene function and biological role
Gene Function: The CYP2D6 gene encodes cytochrome P450 2D6, a key enzyme in the liver responsible for metabolizing approximately 25 percent of all clinically used medications [1]. This enzyme processes a vast range of drugs, including antidepressants, antipsychotics, beta-blockers, and opioids [1] [2]. Genetic variations in this gene can dramatically alter how quickly or slowly a person processes these substances [3]. This can lead to either a lack of drug efficacy or an increased risk of severe side effects [3]. Understanding CYP2D6 variation is essential for personalizing drug therapies and dosages [4].
Variant Impact: The rs16947 variant is a missense mutation in the CYP2D6 gene that results in an amino acid change from arginine to cysteine at position 296 of the enzyme [1]. This specific change defines the common CYP2D6*2 allele, which was historically considered to have normal activity but has been shown to reduce correct mRNA splicing [5]. Because this variant is present in multiple complex genetic backgrounds, it can influence the metabolism of numerous drugs [2]. It is particularly associated with altered responses to the antipsychotic clozapine and the beta-blocker timolol [1] [4].
Key Insight: Although once thought to be completely neutral, this variant actually reduces correct gene splicing and lowers enzyme expression. It can cause opposite reactions depending on the drug, increasing side-effect risks for some medications while showing a reduced response for others.
Location: CYP2D6. Chromosome 22 · 22q13.2 · 42.1 Mb
Estimated prevalence by population
Global 15.8%; European 11.2%; African 26.8%; East Asian 2.2%; South Asian 14.6%; Americas 11.8%; Ashkenazi 15.5%; Finnish 15.2%; Middle Eastern 26.0%; Amish 5.3%.
Estimated AA genotype frequency.
Global 45.8%; European 44.5%; African 49.9%; East Asian 25.2%; South Asian 47.2%; Americas 45.1%; Ashkenazi 47.7%; Finnish 47.6%; Middle Eastern 50.0%; Amish 35.5%.
Estimated AG genotype frequency.
Global 38.5%; European 44.3%; African 23.3%; East Asian 72.6%; South Asian 38.2%; Americas 43.1%; Ashkenazi 36.7%; Finnish 37.3%; Middle Eastern 24.0%; Amish 59.2%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Pharmacogenomics
Antidepressant & Psychiatric Drug Response
Clozapine Response. Evidence: 5/10. Source: PMID 38765922. Typical Metabolism.
Cardiovascular Drug Response
Beta-Blocker Response. Evidence: 5/10. Source: PMID 20925579. Higher Bradycardia Risk.
Anesthesia Response
Sedative Sensitivity. Evidence: 5/10. Source: PMID 37693312. Typical Sensitivity.
Drug Metabolism Enzyme Activity
CYP2D6 Splicing. Evidence: 3/10. Source: PMID 18698231. Typical Splicing.
Showing effects for A/G genotype
CYP2D6 Splicing. Evidence: 3/10. Source: PMID 18698231. Reduced Splicing.
Showing effects for G/G genotype
Clozapine Response. Evidence: 5/10. Source: PMID 38765922. Slower Metabolism.
Beta-Blocker Response. Evidence: 5/10. Source: PMID 20925579. Typical Response.
Sedative Sensitivity. Evidence: 5/10. Source: PMID 37693312. Lower Sensitivity.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
People with the A/A genotype carry two copies of the reference allele, which is associated with typical metabolism for several CYP2D6-processed drugs but presents specific risks for others. Clinical research indicates that this genotype is linked to an increased risk of developing bradycardia, or an abnormally slow heart rate, when using ophthalmic timolol, a beta-blocker commonly prescribed for glaucoma [1]. Conversely, this genotype is associated with typical, efficient metabolism of the antipsychotic medication clozapine, avoiding the slower clearance rates seen with other variants [2]. Because CYP2D6 is highly complex, this single variant is only one piece of the puzzle, and a full diplotype analysis is required to fully map overall enzyme activity [3]. Knowing this status can help guide discussions with healthcare providers regarding cardiovascular monitoring during beta-blocker therapy [1].
Increased risk of slow heart rate from timolol eye drops; Typical clozapine metabolism and clearance.
Sample genotype: AG (Heterozygous)
This heterozygous genotype carries one reference allele and one variant allele, resulting in a mixed profile for drug processing. Individuals with this genotype have been shown to have an elevated risk of experiencing a slow heart rate when treated with the beta-blocker timolol [1]. At the same time, clozapine metabolism remains typical, meaning standard clearance rates and typical side-effect profiles for this antipsychotic are expected [2]. Because the G allele is associated with reduced gene splicing and expression, overall CYP2D6 enzyme activity may be slightly lower than in individuals with fully wild-type profiles [3]. However, because CYP2D6 is highly polymorphic, this single marker cannot definitively determine overall metabolizer status without a complete diplotype analysis [4].
Increased risk of slow heart rate from timolol eye drops; Typical clozapine metabolism.
Sample genotype: GG (Homozygous)
Individuals with the G/G genotype carry two copies of the variant allele, which is the defining marker of the CYP2D6*2 haplotype. This genotype is associated with slower metabolism of the antipsychotic drug clozapine, which can lead to higher drug concentrations in the blood [1]. Consequently, G/G carriers have an increased risk and severity of adverse reactions to clozapine, including low white blood cell counts, elevated liver enzymes, and elevated creatine kinase [1]. Additionally, this genotype may respond less strongly to the sedative dexmedetomidine [2]. On the positive side, G/G carriers exhibit a typical response to the beta-blocker timolol, avoiding the slow heart rate risks associated with the A allele [3]. Because rs16947 reduces correct mRNA splicing, it can lower overall CYP2D6 expression, though other co-inherited variants can sometimes offset this effect [4].
Slower clozapine metabolism and higher side-effect risk; May respond less strongly to dexmedetomidine; Typical response to timolol beta-blockers.
Variants with shared genetic architecture
rs1065852 · CYP2D6 Gene · Chr 22 · Medication Response
rs28371725 · CYP2D6 Gene · Chr 22 · Medication Metabolism
rs3892097 · CYP2D6 Gene · Chr 22 · Medication Response
Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine.
Content updated August 2026.
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