What you carry at this position in your DNA and what research says about it.
Medication Response: 6/10 evidence, 9 publications.
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Sample genotype (not yours): G/G
Typical Medication Response
Normal transporter activity ensures typical processing of various medications. Standard doses of drugs like tramadol, morphine, and sumatriptan are metabolized at expected rates.
What this genotype means: Typical drug clearance rates; Standard risk of medication side effects.
Sample genotype (not yours): A/A
Severely Slower Medication Metabolism
Complete loss of transporter activity significantly impairs the clearance of many medications. This can lead to much higher drug exposure and an elevated risk of adverse reactions.
What this genotype means: Significantly slower clearance of sumatriptan and morphine; Elevated risk of drug-related side effects; Reduced tramadol activation, so less pain relief from it.
Sample genotype (not yours): G/A
Slower Medication Metabolism
Reduced transporter activity leads to slower clearance of several common medications. This can increase the risk of side effects for some drugs while making others more potent.
What this genotype means: Slower clearance of sumatriptan and morphine; Increased risk of side effects from fenoterol; Potentially greater sensitivity to tramadol.
Gene function and biological role
Gene Function: The SLC22A1 gene encodes the organic cation transporter 1 (OCT1), a major transport protein primarily located in the liver [1]. OCT1 plays a critical role in taking up various organic cations, including many commonly prescribed drugs, from the bloodstream into liver cells for processing and elimination [1]. It is also involved in transporting essential nutrients like thiamine (vitamin B1) [2]. Variations in this gene can significantly alter how the body processes medications, leading to differences in drug efficacy and the risk of side effects [1].
Variant Impact: The rs34059508 variant, also known as p.Gly465Arg, is a missense mutation in the SLC22A1 gene that alters a single amino acid in the OCT1 protein. This specific change replaces a glycine residue with arginine, which impairs the proper localization of the transporter and leads to a complete loss of its functional activity [1]. As a result, the liver's ability to take up and clear certain medications is severely compromised [1]. This variant is relatively rare globally but is found at low frequencies in European and some Latino populations.
Key Insight: This variant completely inactivates the OCT1 transporter, which can more than double the blood levels of certain common medications like sumatriptan.
Location: SLC22A1. Chromosome 6 · 6q25.3 · 160.2 Mb
Estimated prevalence by population
Global 97.2%; European 95.3%; African 99.2%; East Asian 100.0%; South Asian 99.5%; Americas 98.2%; Ashkenazi 98.2%; Finnish 98.3%; Middle Eastern 97.3%; Amish 95.7%.
Estimated GG genotype frequency.
Global 2.7%; European 4.7%; African 0.8%; East Asian 0.0%; South Asian 0.5%; Americas 1.8%; Ashkenazi 1.8%; Finnish 1.7%; Middle Eastern 2.7%; Amish 4.3%.
Estimated GA genotype frequency.
Global < 0.1%; European 0.1%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi < 0.1%; Finnish < 0.1%; Middle Eastern < 0.1%; Amish < 0.1%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Pharmacogenomics
Pain Medication Response
Morphine Response. Evidence: 6/10. Source: PMID 23859569. Typical Metabolism.
Tramadol Response. Evidence: 5/10. Source: PMID 27541716. Typical Response.
Neurology & Mental Health
Headache & Migraine
Sumatriptan Response. Evidence: 5/10. Source: PMID 26659468. Typical Metabolism.
Organ Systems
Respiratory Health
Fenoterol Sensitivity. Evidence: 5/10. Source: PMID 28791698. Typical Response.
Nutrition & Metabolism
Blood Chemistry & Metabolites
Methylsuccinoylcarnitine Levels. Evidence: 5/10. Source: PMID 37277652. Typical Levels.
Showing effects for A/A genotype
Morphine Response. Evidence: 6/10. Source: PMID 23859569. Slower Metabolism.
Tramadol Response. Evidence: 5/10. Source: PMID 27541716. Higher Sensitivity.
Sumatriptan Response. Evidence: 5/10. Source: PMID 26659468. Slower Metabolism.
Fenoterol Sensitivity. Evidence: 5/10. Source: PMID 28791698. Higher Side Effects.
Methylsuccinoylcarnitine Levels. Evidence: 5/10. Source: PMID 37277652. Elevated Levels.
Showing effects for G/A genotype
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Normal transporter activity ensures typical processing of various medications. Standard doses of drugs like tramadol, morphine, and sumatriptan are metabolized at expected rates [1] [2]. The risk of experiencing unusual side effects from these medications remains at baseline levels [3]. Additionally, cellular uptake of essential nutrients like thiamine proceeds normally, supporting healthy lipid and glucose metabolism. No adjustments to standard therapeutic guidelines are typically indicated based on this genotype.
Typical drug clearance rates; Standard risk of medication side effects.
Sample genotype: AA (Homozygous)
Complete loss of transporter activity significantly impairs the clearance of many medications. Systemic exposure to drugs like sumatriptan, morphine, and fenoterol is substantially elevated, which can increase the likelihood of adverse reactions [1] [2] [3]. For example, individuals with two inactive copies of the transporter show much higher blood concentrations of sumatriptan [1]. Conversely, the activation of tramadol is reduced [4]. Elevated levels of certain metabolites like methylsuccinoylcarnitine are also observed in both plasma and urine [5].
Significantly slower clearance of sumatriptan and morphine; Elevated risk of drug-related side effects; Reduced tramadol activation, so less pain relief from it.
Sample genotype: GA (Heterozygous)
Reduced transporter activity leads to slower clearance of several common medications. Systemic exposure to drugs like sumatriptan and morphine is increased because the liver takes them up more slowly [1] [2]. This slower metabolism can increase the risk of experiencing drug-related side effects, such as cardiovascular reactions to fenoterol [3]. Conversely, tramadol, a prodrug that requires liver activation, may produce a stronger effect [4]. A single copy of this variant moderately alters overall drug pharmacokinetics.
Slower clearance of sumatriptan and morphine; Increased risk of side effects from fenoterol; Potentially greater sensitivity to tramadol.
Variants with shared genetic architecture
rs12208357 · SLC22A1 Gene · Chr 6 · Cholesterol and Drug Response
rs1564348 · SLC22A1 Gene · Chr 6 · Cholesterol Levels
rs34130495 · SLC22A1 Gene · Chr 6 · Medication Response
OCT1 genetic variants influence the pharmacokinetics of morphine in children.
Content updated August 2026.
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