General Information of Drug Transporter (DT)
DT ID	DTD0006 Transporter Info
Gene Name	SLC22A2
Protein Name	Organic cation transporter 2
Gene ID	6582
UniProt ID	O15244
Genetic Polymorphisms of DT (GPD)
Genetic Polymorphism	rs316019
Site of GPD	chr6:160249250 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	A>C
Minor Allele Frequency	A=0.1374/688 (Global)
Allele A	Click to Show/Hide the Full List of Affected Drugs:         18 Drugs in Total
Cisplatin	Drug Info	Neoplasm	Correlated with the decreased ototoxicity risk in patients (compare with allele C)		[ 1], [ 2]
Daunorubicin	Drug Info	Neoplasm	Irrelevant to the likelihood of cardiotoxicity in patients (compare with Allele C)		[ 3]
Doxorubicin	Drug Info	Neoplasm	Irrelevant to the likelihood of cardiotoxicity in patients (compare with Allele C)		[ 3]
Metformin	Drug Info	Healthy Individuals	Irrelevant to the steady-state concentration of metformin in healthy individuals (compare with Allele C)		[ 4]
Sulfonamides, Urea Derivatives	N.A.	Adverse Events	Allele A is not associated with response to sulfonamides, urea derivatives in people with Diabetes Mellitus as compared to allele C.		[ 5]
Tipiracil Hydrochloride	N.A.	Adverse Events	Allele A is not associated with response to tipiracil hydrochloride and trifluridine in people with Colorectal Neoplasms as compared to allele C.		[ 6]
Trifluridine	N.A.	Adverse Events	Allele A is not associated with response to tipiracil hydrochloride and trifluridine in people with Colorectal Neoplasms as compared to allele C.		[ 6]
Metformin	N.A.	Nephrotoxicity	Allele A is not associated with CLrenal nor the secretory clearance (CLsec) of metformin when exposed to metformin in healthy individuals as compared to allele C.		[ 7]
Anthracyclines And Related Substances	N.A.	Nephrotoxicity	Allele A is associated with decreased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to allele C.		[ 8]
Metformin	N.A.	Drug Toxicity	Allele A is not associated with steady-state concentration of metformin in healthy individuals as compared to allele C.		[ 4]
Cisplatin	N.A.	Ototoxicity	Allele A is associated with decreased risk of Ototoxicity when treated with cisplatin as compared to allele C.		[ 2]
Daunorubicin	N.A.	Cardiotoxicity	Allele A is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele C.		[ 3]
Doxorubicin	N.A.	Cardiotoxicity	Allele A is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele C.		[ 3]
Metformin	N.A.	Cardiotoxicity	Allele A is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.		[ 9]
Cisplatin	N.A.	Ototoxicity	Allele A is associated with decreased risk of Ototoxicity when treated with cisplatin in people with Neoplasms.		[ 1]
Anthracyclines And Related Substances	N.A.	Neoplasms	Allele A is associated with decreased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to allele C.		[ 8]
Anthracyclines And Related Substances	N.A.	Neoplasms	Allele A is not associated with likelihood of cardiotoxicity when exposed to daunorubicin and doxorubicin in children with Neoplasms as compared to allele C.		[ 3]
Anthracyclines	N.A.	Neoplasm	Correlated with the decreased likelihood of cardiotoxicity in patients (compare with allele C)		[ 8]
Allele C	Click to Show/Hide the Full List of Affected Drugs:           5 Drugs in Total
Cisplatin	Drug Info	Testicular Neoplasm	Irrelevant to the likelihood of ototoxicity in patients (compare with Allele A)		[ 10]
Cisplatin	N.A.	Ototoxicity	Allele C is not associated with likelihood of Ototoxicity when treated with cisplatin in men with Testicular Neoplasms as compared to allele A.		[ 10]
Ranitidine	N.A.	Adverse Events	Allele C is not associated with transport of ranitidine as compared to allele A.		[ 11]
Metformin	N.A.	Nephrotoxicity	Allele C is not associated with exposure to metformin as compared to allele A.		[ 12]
Cisplatin	N.A.	Ototoxicity	Allele C is not associated with risk of Ototoxicity due to cisplatin in children with Neoplasms as compared to allele A.		[ 13]
Genotype AC	Click to Show/Hide the Full List of Affected Drugs:         12 Drugs in Total
Cisplatin	Drug Info	Neoplasm	Correlated with the decreased nephrotoxicity risk in patients (compare with genotype CC)		[ 14]
Metformin	N.A.	Cardiotoxicity	Genotype AC is associated with lack of increase in metformin concentrations when treated with metformin and trimethoprim in healthy individuals.		[ 15]
Trimethoprim	N.A.	Cardiotoxicity	Genotype AC is associated with lack of increase in metformin concentrations when treated with metformin and trimethoprim in healthy individuals.		[ 15]
Cisplatin	N.A.	Nephrotoxicity	Genotype AC is associated with increased severity of nephrotoxicity due to cisplatin in people with Neoplasms as compared to genotype CC.		[ 16]
Cisplatin	N.A.	Nephrotoxicity	Genotype AC is associated with decreased risk of nephrotoxicity when treated with cisplatin in people with Neoplasms as compared to genotype CC.		[ 14]
Anthracyclines And Related Substances	N.A.	Neoplasms	Patients with the AC genotype may have decreased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to patients with genotype CC and increased likelihood as compared to patients with the AA genotype, although this has been contradicted in one study. Other genetic and clinical factors may also influence the risk of toxicity to anthracyclines and related substances.		[ 8]
Cisplatin	N.A.	Neoplasms	Genotype AC is associated with decreased risk of nephrotoxicity when treated with cisplatin in people with Neoplasms as compared to genotype CC.		[ 14]
Cisplatin	N.A.	Neoplasms	Genotype AC is associated with increased severity of nephrotoxicity due to cisplatin in people with Neoplasms as compared to genotype CC.		[ 16]
Cisplatin	N.A.	Ototoxicity	Patients with the AC genotype may have increased risk of cisplatin-induced ototoxicity as compared to patients with AA genotype. However, other studies have failed to find an association. Other clinical and genetic factors may also influence the risk of toxicity to cisplatin.		[ 13]
Metformin	N.A.	Ototoxicity	Patients with the AC genotype may have decreased clearance of metformin as compared to patients with the CC genotype, however this is contradicted by one study. Other genetic and clinical factors may also influence clearance of metformin.		[ 19]
L-tryptophan	N.A.	Ototoxicity	Patients with the AC genotype may have decreased clearance of L-tryptophan as compared to patients with the CC genotype, but an increased clearance as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response.		[ 20]
Platinum Compounds	N.A.	Non-small Cell Lung Carcinoma	Patients with the AC genotype and non-small cell lung cancer may have increased severity of toxicity, specifically hepatotoxicity, when taking platinum-based compounds compared to patients with the CC genotype. Other clinical and genetic factors may affect risk of toxicity.		[ 21]
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:         14 Drugs in Total
L-Tryptophan	Drug Info	Depression	Correlated with the increased drug clearance (compare with genotypes AA + AC)		[ 18]
Metformin	Drug Info	Healthy Individuals	Correlated with the increased drug clearance in healthy individuals (compare with genotype AC)		[ 17]
Cisplatin	Drug Info	Neoplasm	Irrelevant to the increased likelihood of nephrotoxicity in patients (compare with genotypes AA + AC)		[ 22]
Dolutegravir	N.A.	Discontinuation	Genotype CC is not associated with likelihood of Discontinuation and adverse events when treated with dolutegravir in people with HIV infectious disease as compared to genotype AC.		[ 23]
Dolutegravir	N.A.	Adverse Events	Genotype CC is not associated with likelihood of Discontinuation and adverse events when treated with dolutegravir in people with HIV infectious disease as compared to genotype AC.		[ 23]
Metformin	N.A.	Adverse Events	Genotype CC is associated with increased clearance of metformin in healthy individuals as compared to genotype AC.		[ 17]
Cisplatin	N.A.	Nephrotoxicity	Genotype CC is not associated with increased likelihood of nephrotoxicity when treated with cisplatin in people with Neoplasms as compared to genotypes AA + AC.		[ 22]
Metformin	N.A.	Drug Toxicity	Genotype CC is associated with increased likelihood of Drug Toxicity when treated with metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AA + AC.		[ 24]
L-tryptophan	N.A.	Cardiotoxicity	Genotype CC is associated with increased clearance of l-tryptophan as compared to genotypes AA + AC.		[ 18]
Anthracyclines And Related Substances	N.A.	Neoplasms	Patients with the CC genotype may have increased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to patients with genotype AC or AA, although this has been contradicted in one study. Other genetic and clinical factors may also influence the risk of toxicity to anthracyclines and related substances.		[ 8]
Cisplatin	N.A.	Neoplasms	Genotype CC is not associated with increased likelihood of nephrotoxicity when treated with cisplatin in people with Neoplasms as compared to genotypes AA + AC.		[ 22]
Cisplatin	N.A.	Neoplasms	Patients with the CC genotype may have increased risk of nephrotoxicity, as measured by serum creatinine, in response to cisplatin treatment as compared to patients with the AC genotype however studies with other biomarkers showed conflicting results. Other genetic and clinical factors may also influence a patient's risk for toxicity.		[ 14]
Cisplatin	N.A.	Ototoxicity	Patients with the CC genotype may have increased risk of cisplatin-induced ototoxicity as compared to patients with AA genotype. However, other studies have failed to find an association. Other clinical and genetic factors may also influence the risk of toxicity to cisplatin.		[ 13]
Platinum Compounds	N.A.	Non-small Cell Lung Carcinoma	Patients with the CC genotype and non-small cell lung cancer may have decreased severity of toxicity, specifically hepatotoxicity, when taking platinum-based compounds compared to patients with the AA and AC genotypes. Other clinical and genetic factors may affect risk of toxicity.		[ 19]
Genotypes AA + AC	Click to Show/Hide the Full List of Affected Drugs:           5 Drugs in Total
Platinum Compounds	N.A.	Drug Toxicity	Genotypes AA + AC are associated with increased severity of Drug Toxicity when treated with Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to genotype CC.		[ 19]
Platinum Compounds	N.A.	Toxic Liver Disease	Genotypes AA + AC are associated with increased severity of Toxic liver disease when treated with Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to genotype CC.		[ 19]
Metformin	N.A.	Ototoxicity	Genotypes AA + AC is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotype CC.		[ 24]
Platinum Compounds	N.A.	Non-small Cell Lung Carcinoma	Genotypes AA + AC are associated with increased severity of Toxic liver disease when treated with Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to genotype CC.		[ 19]
Platinum compounds	N.A.	Non-Small-Cell Lung Carcinoma	Correlated with the increased severity of drug toxicity in patients (compare with genotype CC); Correlated with the increased severity of toxic liver disease in patients (compare with genotype CC)		[ 19]
Genotype AA	Click to Show/Hide the Full List of Affected Drugs:           6 Drugs in Total
Anthracyclines And Related Substances	N.A.	Neoplasms	Patients with the AA genotype may have decreased likelihood of cardiotoxicity when exposed to anthracyclines and related substances in children with Neoplasms as compared to patients with genotype AC or CC, although this has been contradicted in one study. Other genetic and clinical factors may also influence the risk of toxicity to anthracyclines and related substances.		[ 8]
Cisplatin	N.A.	Neoplasms	Patients with the AA genotype may have reduced but not non-existent risk of nephrotoxicity, as measured by serum creatinine, in response to cisplatin treatment as compared to patients with the CC genotype however studies with other biomarkers showed conflicting results and this geneotype was not reported. Other genetic and clinical factors may also influence a patient's risk for toxicity.		[ 14]
Cisplatin	N.A.	Ototoxicity	Patients with the AA genotype may have decreased risk of cisplatin-induced ototoxicity as compared to patients with AC or CC genotype. However, other studies have failed to find an association. Other clinical and genetic factors may also influence the risk of toxicity to cisplatin.		[ 13]
Metformin	N.A.	Ototoxicity	No patients with the AA genotype were seen in the study population. However, patients with the AC genotype may have decreased clearance of metformin as compared to patients with the CC genotype, however this is contradicted by one study. Other genetic and clinical factors may also influence clearance of metformin.		[ 17]
L-tryptophan	N.A.	Ototoxicity	Patients with the AA genotype may have decreased clearance of L-tryptophan as compared to patients with the AC or CC genotype. Other genetic and clinical factors may also influence a patient's response.		[ 18]
Platinum Compounds	N.A.	Non-small Cell Lung Carcinoma	Patients with the AA genotype and non-small cell lung cancer may have increased severity of toxicity, specifically hepatotoxicity, when taking platinum-based compounds compared to patients with the CC genotype. Other clinical and genetic factors may affect risk of toxicity.		[ 19]
Genetic Polymorphism	rs316003
Site of GPD	chr6:160224800 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>A / C>T
Minor Allele Frequency	C=0.3110/615 (Global)
Genotypes CT + TT	Click to Show/Hide the Full List of Affected Drugs:           2 Drugs in Total
Platinum Compounds	N.A.	Progression-free Survival	Genotypes CT + TT is associated with increased progression-free survival and overall survival when treated with Platinum compounds in people with Lung Neoplasms and Tobacco Use Disorder as compared to genotype CC.		[ 24]
Platinum Compounds	N.A.	Overall Survival	Genotypes CT + TT is associated with increased progression-free survival and overall survival when treated with Platinum compounds in people with Lung Neoplasms and Tobacco Use Disorder as compared to genotype CC.		[ 24]
Allele C	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Platinum Compounds	N.A.	Drug Toxicity	Allele C is not associated with severity of Drug Toxicity when treated with Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.		[ 19]
Genetic Polymorphism	rs316009
Site of GPD	chr6:160254732 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>A / T>C / T>G
Minor Allele Frequency	T=0.0920/182 (Global)
Genotype CC	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Drug Toxicity	Genotype CC is associated with increased likelihood of Drug Toxicity when treated with metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes CT + TT.		[ 22]
Genotype TT	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Ototoxicity	Genotype TT is associated with increased response to metformin in people with Diabetes Mellitus as compared to genotypes CC + CT.		[ 25]
Genetic Polymorphism	rs315978
Site of GPD	chr6:160231826 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	T>C
Minor Allele Frequency	T=0.1350/267 (Global)
Allele T	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Ototoxicity	Allele T is not associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.		[ 26]
Genetic Polymorphism	rs662301
Site of GPD	chr6:160275887 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	C>T
Minor Allele Frequency	C=0.9760/1931 (Global)
Allele T	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Metformin	N.A.	Ototoxicity	Allele T is not associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.		[ 26]
Genetic Polymorphism	rs145450955
Site of GPD	chr6:160250619 (GRCh38.p12)
GPD Type	SNP
Allele(s) in dbSNP	G>A
Minor Allele Frequency	G=0.9990/1977 (Global)
Genotype GG	Click to Show/Hide the Full List of Affected Drugs:           1 Drugs in Total
Lamivudine	N.A.	Nephrotoxicity	Genotype GG is not associated with clearance of lamivudine in healthy individuals as compared to genotype AG.		[ 27]
References
1	Promoter region variation in NFE2L2 influences susceptibility to ototoxicity in patients exposed to high cumulative doses of cisplatin. Pharmacogenomics J. 2017 Dec;17(6):515-520.
2	Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity. Pharmacogenomics. 2015;16(4):323-32.
3	Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr Blood Cancer. 2013 Aug;60(8):1375-81.
4	Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers. Eur J Clin Pharmacol. 2015 Jun;71(6):691-697.
5	Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus. Front Pharmacol. 2018 Apr 6;9:320.
6	Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer. Eur J Cancer. 2017 Nov;86:197-206.
7	A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin. Pharmacogenet Genomics. 2013 Oct;23(10):526-34.
8	Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J Clin Oncol. 2012 May 1;30(13):1422-8.
9	Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis. Clin Pharmacol Ther. 2017 Jun;101(6):763-772.
10	Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer. JAMA Oncol. 2017 Nov 1;3(11):1558-1562.
11	Effects of genetic polymorphisms on the OCT1 and OCT2-mediated uptake of ranitidine. PLoS One. 2017;12(12):e0189521.
12	Influence of pharmacogenetic polymorphisms and demographic variables on metformin pharmacokinetics in an admixed Brazilian cohort. Br J Clin Pharmacol. 2018 May;84(5):987-996.
13	Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study. Pharmacogenomics J. 2020 Apr;20(2):294-305.
14	Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity. Clin Pharmacol Ther. 2009 Oct;86(4):396-402.
15	Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters. Br J Clin Pharmacol. 2013 Nov;76(5):787-96.
16	Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin. Int J Mol Sci. 2017 Jun 22;18(7).
17	Influences of organic cation transporter polymorphisms on the population pharmacokinetics of metformin in healthy subjects. AAPS J. 2013 Apr;15(2):571-80.
18	Pharmacogenetics meets metabolomics: discovery of tryptophan as a new endogenous OCT2 substrate related to metformin disposition. PLoS One. 2012;7(5):e36637.
19	Associations of genetic polymorphisms of the transporters organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), and ATP-binding cassette subfamily C member 2 (ABCC2) with platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients. Chin J Cancer. 2016 Sep 2;35(1):85.
20	Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a renoprotective effect of ERCC1 polymorphisms. Pharmacogenomics. 2011 Oct;12(10):1417-27.
21	Dolutegravir and Risk of Neuropsychiatric Adverse Events: a Pharmacogenetic Study. J Infect Dis. 2025 Feb 26.
22	PCK1 and SLC22A2 gene variants associated with response to metformin treatment in type 2 diabetes. PLoS One. 2025;20(2):e0305511.
23	Implication of critical pharmacokinetic gene variants on therapeutic response to metformin in Type 2 diabetes. Pharmacogenomics. 2018 Jul 01;19(11):905-911.
24	The Association Between Genetic Polymorphisms of Transporter Genes and Prognosis of Platinum-Based Chemotherapy in Lung Cancer Patients. Pharmgenomics Pers Med. 2022;15:817-825.
25	A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin. Clin Pharmacol Ther. 2016 Nov;100(5):537-547.
26	The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients. Gene. 2024 Nov 15;927:148648.
27	Effects of OCT2 c.602C > T genetic variant on the pharmacokinetics of lamivudine. Xenobiotica. 2013 Jul;43(7):636-40.

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