What you carry at this position in your DNA and what research says about it.
Medication Response: 6/10 evidence, 11 publications.
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Sample genotype (not yours): A/A
Variable Drug Sensitivity
This genotype is associated with a better response to metformin and a lower risk of cisplatin-induced hearing loss, and a lower risk of liver toxicity from platinum chemotherapies.
What this genotype means: Better therapeutic response to metformin; Decreased risk of cisplatin-induced hearing damage; Increased risk of liver toxicity from platinum chemotherapies.
Sample genotype (not yours): A/C
This genotype offers a better response to metformin and lower cisplatin hearing loss risk, and lower liver toxicity, though with a higher risk of chemotherapy-induced kidney injury.
What this genotype means: Better therapeutic response to metformin; Decreased risk of cisplatin-induced hearing damage; Increased risk of cisplatin-induced kidney damage.
Sample genotype (not yours): C/C
Typical Drug Transport and Response
This common genotype is associated with a higher risk of platinum-related liver toxicity, and carries a higher risk of metformin-related side effects and a poorer overall response to metformin.
What this genotype means: Typical baseline risk of cisplatin-induced hearing damage; Increased risk of metformin-related adverse drug reactions; Typical baseline risk of liver toxicity from platinum chemotherapies.
Gene function and biological role
Gene Function: The SLC22A2 gene encodes the organic cation transporter 2 (OCT2), a protein primarily found in the kidneys [1]. This transporter plays a critical role in filtering and excreting various organic cations, including many common prescription medications, from the bloodstream into the urine [2]. By regulating the active secretion of these compounds, the transporter directly influences drug clearance and systemic drug levels [3]. It is particularly vital for the renal clearance of the first-line type 2 diabetes medication metformin [4]. Additionally, it facilitates the cellular uptake of platinum-based chemotherapy drugs, which can lead to localized tissue accumulation and toxicity [5].
Variant Impact: This missense variant causes an amino acid substitution from serine to alanine at position 270 of the transporter protein. This structural alteration significantly changes the transporter's binding affinity and excretion rate for several therapeutic drugs [3]. The alteration affects how efficiently the kidneys clear metformin, potentially altering blood sugar control and the risk of side effects [4]. Furthermore, the change modifies the uptake of platinum-based chemotherapy agents like cisplatin, which can alter the risk of severe side effects such as hearing loss and kidney damage [6]. Because the transporter is highly active in renal tubules, this single genetic change is a major determinant of personal drug pharmacokinetics [7].
Key Insight: A single amino acid change in this kidney transporter protects against both chemotherapy-induced hearing loss and platinum-related liver toxicity, while shaping the body's response to metformin.
Location: SLC22A2. Chromosome 6 · 6q25.3 · 160.2 Mb
Estimated prevalence by population
Global 1.3%; European 1.0%; African 2.3%; East Asian 1.7%; South Asian 1.5%; Americas 0.7%; Ashkenazi 2.1%; Finnish 0.4%; Middle Eastern 2.7%; Amish 1.0%.
Estimated AA genotype frequency.
Global 19.7%; European 17.8%; African 25.7%; East Asian 22.5%; South Asian 21.5%; Americas 15.1%; Ashkenazi 25.0%; Finnish 11.2%; Middle Eastern 27.3%; Amish 18.2%.
Estimated AC genotype frequency.
Global 79.0%; European 81.3%; African 72.0%; East Asian 75.8%; South Asian 77.0%; Americas 84.2%; Ashkenazi 72.9%; Finnish 88.5%; Middle Eastern 70.0%; Amish 80.8%.
Estimated CC genotype frequency.
Showing effects for A/A genotype
Pharmacogenomics
Diabetes Medication Response
Metformin Response. Evidence: 5/10. Source: PMID 39928707. Stronger Response.
Chemotherapy Response
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 25823781. Decreased Risk.
Cisplatin Kidney Damage. Evidence: 6/10. Source: PMID 28640195. Typical Risk.
Chemotherapy Toxicity. Evidence: 5/10. Source: PMID 27590272. Decreased Severity.
Showing effects for A/C genotype
Cisplatin Kidney Damage. Evidence: 6/10. Source: PMID 28640195. Increased Severity.
Chemotherapy Toxicity. Evidence: 5/10. Source: PMID 27590272. Intermediate Severity.
Showing effects for C/C genotype
Metformin Response. Evidence: 5/10. Source: PMID 39928707. Higher Toxicity Risk.
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 25823781. Typical Risk.
Chemotherapy Toxicity. Evidence: 5/10. Source: PMID 27590272. Increased Severity.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Carrying two copies of the minor A allele alters the OCT2 transporter in a way that slows down the clearance of certain compounds while reducing the uptake of others. Clinical studies indicate that this genotype leads to a significantly better therapeutic response to the diabetes drug metformin [1]. It also provides a protective effect against cisplatin-induced ototoxicity, resulting in a decreased risk of permanent hearing damage during cancer treatment [2]. This same altered transport also reduces hepatic uptake of platinum drugs, lowering the severity of chemotherapy-related liver damage [3]. The reduced transport activity means some drugs remain in circulation longer, while others are prevented from entering sensitive tissues where they cause harm.
Better therapeutic response to metformin; Decreased risk of cisplatin-induced hearing damage; Increased risk of liver toxicity from platinum chemotherapies.
Sample genotype: AC (Heterozygous)
Carrying one copy of the minor A allele results in a mixed transport profile for several common medications. Research shows that individuals with this heterozygous genotype experience a more favorable therapeutic response to metformin therapy [1]. There is also a documented protective effect against cisplatin-induced hearing loss, as the altered transporter reduces drug accumulation in the inner ear [2]. However, this same genetic variation is associated with an increased severity of cisplatin-induced kidney damage, as measured by elevated kidney injury biomarkers [3]. In contrast, this genotype is associated with a lower risk of severe platinum-related liver damage due to reduced hepatic uptake [4].
Better therapeutic response to metformin; Decreased risk of cisplatin-induced hearing damage; Increased risk of cisplatin-induced kidney damage; Increased risk of liver toxicity from platinum chemotherapies.
Sample genotype: CC (Homozygous)
Carrying two copies of the major C allele represents the standard, highly active form of the OCT2 transporter. Because the transporter operates at baseline capacity, metformin is cleared rapidly from circulation, which can sometimes lead to a less optimal therapeutic response in type 2 diabetes patients [1]. This highly active transport state is also associated with an increased likelihood of metformin-related adverse drug reactions and general toxicity [2]. When undergoing cisplatin chemotherapy, this genotype presents a typical, baseline risk of hearing damage because the drug is readily transported into sensitive tissues [3]. The high transport activity also drives greater platinum-drug uptake into the liver, giving this genotype a higher risk of liver toxicity during chemotherapy [4].
Typical baseline risk of cisplatin-induced hearing damage; Increased risk of metformin-related adverse drug reactions; Typical baseline risk of liver toxicity from platinum chemotherapies.
Variants with shared genetic architecture
rs2279463 · SLC22A2 Gene · Chr 6 · Kidney Test Accuracy
rs3127573 · SLC22A2 Gene · Chr 6 · Kidney Function
rs9295128 · SLC22A2 Gene · Chr 6 · Healthy Aging
Interaction of Cisplatin with the human organic cation transporter 2.
PCK1 and SLC22A2 gene variants associated with response to metformin treatment in type 2 diabetes.
Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity.
Content updated August 2026.
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