Gene:
SLC22A1
solute carrier family 22 (organic cation transporter), member 1

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

List of all SLC22A1 variant annotations

Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA *1 N/A N/A N/A
No VIP available CA VA *2 N/A N/A N/A
No VIP available CA VA *3 N/A N/A N/A
No VIP available CA VA *4 N/A N/A N/A
No VIP available CA VA *5 N/A N/A N/A
rs12208357 160543148C>T, 181C>T, 64712605C>T, Arg61Cys, R61C, SLC22A1: R61C, SLC22A1:148C>T
C > T
Missense
Arg61Cys
No VIP available CA VA
rs2282143 1022C>T, 160557643C>T, 64727100C>T, Pro341Leu, SLC22A1: P341L
C > T
Missense
Pro341Leu
rs34059508 1386-1170G>A, 1386-1170G>C, 1393G>A, 1393G>C, 160575837G>A, 160575837G>C, 64745294G>A, 64745294G>C, G465R, Gly465Arg, SLC22A1: G465R, SLC22A1:1393G>A
G > A
G > C
Intronic
Gly465Arg
rs34130495 1201G>A, 160560824G>A, 64730281G>A, Gly401Ser, SLC22A1: G401S
G > A
Missense
Gly401Ser
No VIP available CA VA
rs35167514 1258delA, 160560881delA, 64730338delA, Met420Terfs, part of SLC22A1:M420del
A > -
Frameshift
Met420null
No VIP available No Clinical Annotations available VA
rs36056065 1276+1delG, 1276+1delGinsGTAAGTTG, 160560900delG, 160560900delGinsGTAAGTTG, 64730357delG, 64730357delGinsGTAAGTTG
GTAAGTTG > -
Intronic
No VIP available No Clinical Annotations available VA
rs461473 160543562G>A, 411+184G>A, 64713019G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs55918055 160543229T>A, 160543229T>C, 262T>A, 262T>C, 64712686T>A, 64712686T>C, Cys88Arg, Cys88Ser
T > C
T > A
Missense
Cys88Arg
Cys88Ser
No VIP available CA VA
rs622342 1386-2964C>A, 1386-4141C>A, 160572866C>A, 64742323C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs628031 1222A>G, 160560845A>G, 64730302A>G, Met408Val
A > G
Missense
Met408Val
No VIP available No Clinical Annotations available VA
rs683369 160551204G>C, 480G>C, 64720661G>C, Leu160Phe
G > C
Missense
Leu160Phe
rs72552763 1260_1262delGAT, 160560883_160560885delGAT, 64730340_64730342delGAT, Met420_Ile421delinsIle
GAT > -
Non-synonymous
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142

Overview

Alternate Names:  None
Alternate Symbols:  OCT1
PharmGKB Accession Id: PA329

Details

Cytogenetic Location: chr6 : q25.3 - q25.3
GP mRNA Boundary: chr6 : 160542863 - 160579750
GP Gene Boundary: chr6 : 160532863 - 160582750
Strand: plus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Organic Cationic Transporter 1 (OCT1, encoded by gene SLC22A1) is one of the three similar polyspecific cationic transporters mediating the uptake of many organic cations from the blood into epithelial cells. SLC22A1 is located in a cluster on chromosome 6 and contains seven exons and six introns. It can produce several alternatively spliced mRNA isoforms [Article:11388889]. Similar to other members of the SLC22 family, the OCT1 protein contains 12 predicted alpha-helical transmembrane domains and a long hydrophilic loop between transmembrane domains 1 and 2 [Articles:23506881, 12719534]. OCT1 is one of the major hepatic-uptake transporters located on the sinusoidal membrane of hepatocytes. It has substrate selectivity for a variety of endogenous ligands (dopamine, serotonin, choline) as well as cationic drugs, such as metformin, cimetidine, imatinib, oxaliplatin, and tramadol and agmatine [Articles:23506881, 21562485, 16436500, 14576340, 23223357].

Expression
SLC22A1 is predominantly expressed in the liver, and to a lesser extent, in the adrenal gland, lung, kidney as well as other tissues [Articles:17496207, 17473959]. Constitutive expression of SLC22A1 may be mediated by transcription factors. For example, transcriptional activation of SLC22A1 can be mediated by binding of Hepatocyte Nuclear factor 4-alpha (HNF4A) to DNA response elements adjacent to the gene [Article:16436500]. The role of Hepatocyte Nuclear factor 1 may be even a stronger regulator of SLC22A1 in the human liver as high HNF1 expression significantly correlated with high OCT1 expression in human liver samples. Furthermore, electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the specific binding of HNF1 to the intron 1 evolutionary conserved region of SLC22A1 [Article:23922447]. Additionally, the ubiquitously expressed and constitutively active transcriptional factor USF1 was shown to bind in the proximal promoter region and to modulate the basal expression of OCT1 [Article:18845576]. Furthermore, studies demonstrated that SLC22A1 gene expression can also be induced by PPAR agonist receptors alpha and gamma [Article:15458920]. In a separate study, rifampin induced OCT1 expression and hepatic uptake of metformin, which in turn led to enhanced glucose-lowering properties [Article:21270793]. Rifampin could therefore be considered a potential inducer of SLC22A1.

SLC22A1 may also be regulated via epigenetic silencing. A recent report showed that DNA methylation of SLC22A1 is associated with reduced SLC22A1 expression levels in human hepatocellular carcinoma [Article:22196450]. Given the role of this transporter in the cellular uptake of anticancer drugs, the study proposed that methylation of SLC22A1 may result in substantial variability of treatment response to various anti-cancer drugs.

Drug-drug Interactions
OCTs play an important role in transporting many commonly used drugs. Drug-drug interaction (DDI) by inhibition of OCT transporters may be clinically relevant. Proton pump inhibitors have been shown to inhibit metformin uptake by OCT1 and other OCTs in a concentration dependent manner in vitro, but they themselves are not substrates of these transporters [Article:21779389]. More recently, treatment of sitagliptin with metformin in MDCK-OCT1 and HepG2 cells resulted in reduced level of phosphorylated AMPK, suggesting the inhibitory potential of sitagliptin on OCT1 may attenuate the first step of metformin action [Article:20863201]. However, it is important to consider that HepG2 cell lines do not endogenously express OCT1, so the results from this study should be interpreted carefully. In a study by Ahlin et al, metformin uptake was inhibited by concomitantly administered drugs that inhibit OCT1 (such as verapamil and amitriptyline) at clinically relevant concentrations in the OCT1-reference, V408M but especially in M420del. The increased sensitivity to drug inhibition in OCT1 variants suggesting that reduced OCT1 function can lead to an enhanced risk of DDIs occurring in individuals carrying these variants [Article:20567254]. In a separate study, OCT1-mediated metformin and 1-methyl-4-phenylpyridinium (MPP+) uptake were significantly inhibited by repaglinide and rosiglitazone, demonstrating that alterations of uptake transporter function by oral antidiabetic drugs need to be considered as potential mechanisms underlying drug-drug interaction [Article:18314419]. Despite strong evidence from the described in vitro studies, it is important to note that there has not yet been an in-vivo study investigating these potential drug-drug interactions with OCT1.

Important variants of SLC22A1
A number of SLC22A1 polymorphisms have been associated with functional changes in protein activity as well as drug disposition, response and toxicity. Four nonsynonymous SLC22A1 variants that have been most extensively studied are rs12208357, rs34130495, OCT1 420 deletion (rs35167514, rs34305973, rs35191146, rs72552763), and rs34059508. All four variants may impact the pharmacokinetics and pharmacodynamics of metformin, tropisetron, ondansetron, morphine and tramadol.

Clinical associations between SLC22A1 variant alleles and drug disposition, response, and toxicity

Metformin and Type 2 Diabetes
The role of SLC22A1 polymorphisms in metformin clinical pharmacology has been extensively studied. Several genetic polymorphisms have been identified to be clinically significant predictors of metformin exposure and response. Of particular note are four variants, rs12208357, rs34130495, OCT1 420 deletion (rs35167514, rs34305973, rs35191146, rs72552763), and rs34059508. In vitro, all four polymorphisms were associated with reduced metformin uptake and altered levels of phosphorylated AMPK in HEK293 cells [Article:17476361]. Shu et al initially characterized these polymorphisms in healthy volunteer studies [Articles:17476361, 17609683]. In one study, carriers of any one of the four reduced function OCT1 allele exhibited a higher area under the plasma concentration time curve (AUC), higher maximal plasma concentration (Cmax), and lower oral volume of distribution (V/F) [Article:17609683]. In another study by Shu, the glucose-lowering effect of metformin was significantly reduced in individuals carrying at least one reduced function OCT1 allele from the glucose tolerance tests [Article:17476361]. In a study with healthy volunteers, carriers of reduced function OCT1 allele had higher renal clearances [Article:19536068]. In a separate study by Christensen et al, the number of reduced function OCT1 alleles (including the OCT1 420 deletion SNP rs72552763), was associated with decreased metformin steady-state trough concentrations and increased HbA1c levels [Article:21989078]. Finally, in a study by Becker, minor allele of rs622342 (with a population frequency of 27% in Caucasians), was associated with a reduction in HbA1c levels [Articles:19381165, 20690652, 19898263]. It is important to highlight a few controversies that underlie the findings of genetic variants in Metformin pharmacokinetics and response. For example, none of the variants found relevant in the Shu et al study reached statistical significance in Becker's Rotterdam study. In the Rotterdam study, only an intronic variant (rs622342) was found to be significant. Furthermore, in the Christensen et al. paper, the OCT1 deletion finding with metformin exposure level was opposite to what was observed in the Shu study. Overall, more reproducibility by independent research groups is required for OCT1 variants to be clinically actionable.

SLC22A1 variants have also been associated with metformin related side effects. A study by Tarasova et al. identified two coding variants, rs36056065 and rs628031 that were associated with the presence of side effects of metformin. Particularly, the authors noted that the presence of either variant may predispose a patient towards an increase in GI related side effects following metformin therapy [Article:22735389].

Metformin and polycystic ovary syndrome (PCOS)
In addition to being the first in line therapy for type 2 Diabetes, Metformin is also used to treat polycystic ovary syndrome in women. The four aforementioned OCT1 coding variants (rs12208357, rs34130495, the OCT1 420 deletion, and rs34059508) were also studied in women with polycystic ovary syndrome. In this study, carriers of a reduced function OCT1 variant were likely to have reduced lipid (total cholesterol and triglycerides) and insulin responses [Article:20660041].

Imatinib and Chronic Myeloid Leukemia (CML)
Recent studies have demonstrated patients with low expression or activity of OCT1 had a lower probability of achieving a cytogenetic or molecular remission to CML. Improved progression free survival and overall survival was also observed in patients with higher OCT1 expression [Article:18398725]. In a study by Giannoudis et al, the effect of polymorphisms rs628031 (Met408Val) and rs35191146 (420Del) on imatinib uptake and clinical efficacy was investigated [Article:23223357]. In CML cell lines transfected with the M420del and/or rs628031 (M408V), M420del significantly decreased imatinib uptake. Several papers find the uptake of Imatinib via OCT1 controversial. For example, Ann Nies and colleagues showed through transport and inhibition studies that overexpression of functional OCT1 did not lead to increased accumulation of Imatinib. They go on to conclude that cellular uptake of imatinib is independent of OCT1 and therefore OCT1 is not a valid biomarker for imatinib resistance [Article:24352644]. In a separate study the hOCT1 M420 deletion (rs35191146) was linked to clinical outcome of imatinib-treated CML. Patients with this polymorphism demonstrated an increased probability of imatinib treatment failure. In a separate study, patients carrying the GG genotype for SNP rs683369 were at a higher risk of loss of response or treatment failure to imatinib therapy in CML patients [Article:19584153].

Sorafenib and Hepatocellular Carcinoma
There have been recent studies to suggest the importance of OCT1 in the development of hepatocellular carcinoma (HCC). First, there may be downregulation of SLC22A1 protein expression in HCC compared to normal adjacent tissue.[Article:22196450] Secondly, Sorafenib, a tyrosine kinase inhibitor approved for the treatment of HCC, has been recently suggested to be a substrate of OCT1 [Article:23482500]. However, this finding has not been confirmed, as other authors could not measure OCT1-mediated uptake of Sorafenib [Article:19773380]. A more recent study explored the role of OCT1 on sorafenib chemoresistance in HCC cell lines, specifically investigating two novel alternative spliced variants. The paper concluded that these variants, coupled with decreased OCT1 expression, may affect the ability of sorafenib to reach active intracellular levels in the tumor [Article:23532667].

Antiemetic (anti-nausea) drugs
A study by Tzvetkov investigated the impact of OCT1 polymorphisms on the pharmacokinetics and clinical outcome of anti-emetic drugs tropisetron and ondansetron [Article:20921968]. In this study, overexpression of wild type OCT1 led to significant increases in tropisetron uptake, but did not affect the uptake of ondansetron. Clinically, patients were genotyped for five variants already studied in other indications, rs12208357, rs34130495, OCT1 420 deletion, rs34059508, and rs5598055. Carriers of two loss of function OCT1 alleles had higher plasma concentrations and higher clinical efficacy compared with carriers of fully active OCT1.

Morphine and tramadol
OCT1 variants have been associated with responses to pain medications [Article:23835420]. Morphine is a substrate of OCT1 [Article:23835420]. Carriers of loss-of-function OCT1 polymorphisms had a 56% higher mean AUC of morphine compared to non-carriers [Article:23835420]. In children, morphine clearance was significantly lower in homozygote carriers of loss of function OCT1 variants [Article:23859569]. Another study showed that hepatic reuptake of O-desmethyltramadol, but not the pro-drug tramadol, is mediated by SLC22A1 (OCT1). Individuals carrying the loss of function SLC22A1 variants had significantly higher plasma concentrations of O-demethyltramadol and significantly longer miosis, a surrogate marker for opioidergic effect [Article:21562485].

SLC22A1/OCT1 polymorphisms in other areas of research
Three SLC22A1 polymorphisms have been linked to disease progression in patients with Primary Biliary Cirrhosis (PBC) [Article:23612856]. The three variants, rs683369, rs2282143, and rs622342, were associated with jaundice-type progression in Japanese PBC patients using a minor allele recessive genotype model. A genome wide association study in 2782 advanced prostate cancer patients and 4458 controls identified SL22A1 variant rs651164 as a susceptibility locus, with the minor allele A resulting in an odds ratio of 0.87 [Article:21743057]. Polymorphism rs622342, linked to metformin response and PBC disease progression, was also shown in a separate study to be linked to the efficacy of anti-parkinsonian drugs. The minor allele of this SNP was associated with a higher prescribed dose of Levadopa, a known substrate of OCT1 [Article:20690652]. In the same study, this SNP was associated with increased mortality in patients with Parkinsons disease. Interestingly, in a separate genome wide association study on plasma lipids in 100,000 individuals with European ancestry, the minor allele of SLC22A1 SNP rs1564348 was associated with low-density lipoprotein (LDL) at a genome wide level. Further experimental studies are needed to validate the role of OCT1 on LDL levels.

Conclusion
SLC22A1 (OCT1) plays an important role in hepatic uptake of many commonly used drugs. Several SLC22A1 (OCT1) polymorphisms may have clinical consequences. Polymorphisms in SLC22A1 have been identified to significantly alter metformin exposure and response. However it is important to consider the lack of replication by multiple independent research groups, and for this reason, clinical usefulness of these variants should be exercised with caution. Polymorphisms may also affect clinical response to imatinib. But as with metformin, without scientific consensus regarding the role of OCT1 on imatinib uptake, conclusions should be taken with caution. Overall, larger sample sizes are clearly needed to validate the role of SLC22A1 polymorphisms in drug disposition, response and toxicity. Furthermore, in vivo DDI studies are also needed to corroborate the drug-drug interactions that have been observed in vitro in order to warrant clinical consideration of high affinity OCT1 substrates concomitantly prescribed. Future work on OCT1 will also need to address the role of epigenetics as well as the role of other more rare variants on response variability.

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Srijib Goswami, Li Gong, Kathleen Giacomini, Russ B. Altman, Teri E. Klein

Key Publications
  1. Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochemical pharmacology. 2013. Tzvetkov Mladen V, dos Santos Pereira Joao N, Meineke Ingolf, Saadatmand Ali R, Stingl Julia C, Brockmöller Jürgen. PubMed
  2. OCT1 genetic variants influence the pharmacokinetics of morphine in children. Pharmacogenomics. 2013. Fukuda Tsuyoshi, Chidambaran Vidya, Mizuno Tomoyuki, Venkatasubramanian Raja, Ngamprasertwong Pornswan, Olbrecht Vanessa, Esslinger Hope R, Vinks Alexander A, Sadhasivam Senthilkumar. PubMed
  3. The hOCT1 SNPs M420del and M408V alter imatinib uptake and M420del modifies clinical outcome in imatinib-treated chronic myeloid leukemia. Blood. 2013. Giannoudis Athina, Wang Lihui, Jorgensen Andrea L, Xinarianos George, Davies Andrea, Pushpakom Sudeep, Liloglou Triantafilos, Zhang Jieying-Eunice, Austin Gemma, Holyoake Tessa L, Foroni Letizia, Kottaridis Panagiotis D, Müller Martin C, Pirmohamed Munir, Clark Richard E. PubMed
  4. The SLC22 family with transporters of organic cations, anions and zwitterions. Molecular aspects of medicine. 2013. Koepsell Hermann. PubMed
  5. Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients. Pharmacogenetics and genomics. 2012. Tarasova Linda, Kalnina Ineta, Geldnere Kristine, Bumbure Alda, Ritenberga Rota, Nikitina-Zake Liene, Fridmanis Davids, Vaivade Iveta, Pirags Valdis, Klovins Janis. PubMed
  6. The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenetics and genomics. 2011. Christensen Mette M H, Brasch-Andersen Charlotte, Green Henrik, Nielsen Flemming, Damkier Per, Beck-Nielsen Henning, Brosen Kim. PubMed
  7. Genetically Polymorphic OCT1: Another Piece in the Puzzle of the Variable Pharmacokinetics and Pharmacodynamics of the Opioidergic Drug Tramadol. Clinical pharmacology and therapeutics. 2011. Tzvetkov M V, Saadatmand A R, Lötsch J, Tegeder I, Stingl J C, Brockmöller J. PubMed
  8. Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism. 2010. Gambineri Alessandra, Tomassoni Federica, Gasparini Daniela Ibarra, Di Rocco Antonio, Mantovani Vilma, Pagotto Uberto, Altieri Paola, Sanna Stefania, Fulghesu Anna Maria, Pasquali Renato. PubMed
  9. Effects of OCT1 polymorphisms on the cellular uptake, plasma concentrations and efficacy of the 5-HT(3) antagonists tropisetron and ondansetron. The pharmacogenomics journal. 2010. Tzvetkov M V, Saadatmand A R, Bokelmann K, Meineke I, Kaiser R, Brockmöller J. PubMed
  10. Membrane interactions of novicidin, a novel antimicrobial peptide: phosphatidylglycerol promotes bilayer insertion. The journal of physical chemistry. B. 2010. Dorosz Jerzy, Gofman Yana, Kolusheva Sofiya, Otzen Daniel, Ben-Tal Nir, Nielsen Niels Chr, Jelinek Raz. PubMed
  11. Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenetics and genomics. 2010. Becker Matthijs L, Visser Loes E, van Schaik Ron H N, Hofman Albert, Uitterlinden André G, Stricker Bruno H Ch. PubMed
  12. The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clinical pharmacology and therapeutics. 2009. Tzvetkov M V, Vormfelde S V, Balen D, Meineke I, Schmidt T, Sehrt D, Saboli¿ I, Koepsell H, Brockmöller J. PubMed
  13. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. The pharmacogenomics journal. 2009. Becker M L, Visser L E, van Schaik R H N, Hofman A, Uitterlinden A G, Stricker B H C. PubMed
  14. Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Kim Dong Hwan Dennis, Sriharsha Lakshmi, Xu Wei, Kamel-Reid Suzanne, Liu Xiangdong, Siminovitch Katherine, Messner Hans A, Lipton Jeffrey H. PubMed
  15. Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leukemia & lymphoma. 2008. Clark Richard E, Davies Andrea, Pirmohamed Munir, Giannoudis Athina. PubMed
  16. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clinical pharmacology and therapeutics. 2008. Shu Y, Brown C, Castro R A, Shi R J, Lin E T, Owen R P, Sheardown S A, Yue L, Burchard E G, Brett C M, Giacomini K M. PubMed
  17. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. The Journal of clinical investigation. 2007. Shu Yan, Sheardown Steven A, Brown Chaline, Owen Ryan P, Zhang Shuzhong, Castro Richard A, Ianculescu Alexandra G, Yue Lin, Lo Joan C, Burchard Esteban G, Brett Claire M, Giacomini Kathleen M. PubMed
  18. The human organic cation transporter-1 gene is transactivated by hepatocyte nuclear factor-4alpha. The Journal of pharmacology and experimental therapeutics. 2006. Saborowski Michael, Kullak-Ublick Gerd A, Eloranta Jyrki J. PubMed
  19. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). The Journal of pharmacology and experimental therapeutics. 2004. Jonker Johan W, Schinkel Alfred H. PubMed
Variant Summaries rs12208357, rs34059508, rs34130495, rs72552763
Drugs

Haplotype Overview

Haplotypes for SLC22A1 (OCT1) as described in [Article:23859569].

Source: PharmGKB

All alleles in the download file are on the positive chromosomal strand. PharmGKB considers the first haplotype listed in each table as the reference haplotype for that set.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics
    Representation of candidate genes involved in the metabolism of lamivudine and its mechanism of antiviral action.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this gene. To report a pathway, click here.

No related genes are available

Curated Information ?

Curated Information ?

Publications related to SLC22A1: 55

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
The c.480C>G polymorphism of hOCT1 influences imatinib clearance in patients affected by chronic myeloid leukemia. The pharmacogenomics journal. 2014. Di Paolo A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children. Pharmacogenomics. 2014. Venkatasubramanian Raja, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Development of a broad-based ADME panel for use in pharmacogenomic studies. Pharmacogenomics. 2014. Brown Andrew Mk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Parkinson's disease pharmacogenomics: new findings and perspectives. Pharmacogenomics. 2014. Schumacher-Schuh Artur F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Role of solute carrier transporters in pancreatic cancer: a review. Pharmacogenomics. 2014. Lemstrová Radmila, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. Proceedings of the National Academy of Sciences of the United States of America. 2014. Chen Ligong, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: tramadol pathway. Pharmacogenetics and genomics. 2014. Gong Li, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: very important pharmacogene information for SLC22A1. Pharmacogenetics and genomics. 2014. Goswami Srijib, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochemical pharmacology. 2013. Tzvetkov Mladen V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ABCB1 and ABCC1 variants associated with virological failure of first-line protease inhibitors antiretroviral regimens in Northeast Brazil patients. Journal of clinical pharmacology. 2013. Coelho Antonio V C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Hepatocyte nuclear factor 1 regulates the expression of the organic cation transporter OCT1 via binding to an evolutionary conserved region in intron 1 of the OCT1 gene-. The Journal of pharmacology and experimental therapeutics. 2013. O'Brien Valerie P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin. Pharmacogenetics and genomics. 2013. Christensen Mette M H, et al. PubMed
OCT1 genetic variants influence the pharmacokinetics of morphine in children. Pharmacogenomics. 2013. Fukuda Tsuyoshi, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influences of organic cation transporter polymorphisms on the population pharmacokinetics of metformin in healthy subjects. The AAPS journal. 2013. Yoon Hwa, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association between imatinib transporters and metabolizing enzymes genotype and response in newly diagnosed chronic myeloid leukemia patients receiving imatinib therapy. Haematologica. 2013. Angelini Sabrina, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The hOCT1 SNPs M420del and M408V alter imatinib uptake and M420del modifies clinical outcome in imatinib-treated chronic myeloid leukemia. Blood. 2013. Giannoudis Athina, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The SLC22 family with transporters of organic cations, anions and zwitterions. Molecular aspects of medicine. 2013. Koepsell Hermann. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The UCSF-FDA TransPortal: A Public Drug Transporter Database. Clinical pharmacology and therapeutics. 2012. Morrissey K M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Potential effect of pharmacogenetics on maternal, fetal and infant antiretroviral drug exposure during pregnancy and breastfeeding. Pharmacogenomics. 2012. Olagunju Adeniyi, et al. PubMed
Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients. Pharmacogenetics and genomics. 2012. Tarasova Linda, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The role of ATM in response to metformin treatment and activation of AMPK. Nature genetics. 2012. Yee Sook Wah, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
SLC22A1-ABCB1 haplotype profiles predict imatinib pharmacokinetics in Asian patients with chronic myeloid leukemia. PloS one. 2012. Singh Onkar, et al. PubMed
The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenetics and genomics. 2011. Christensen Mette M H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a renoprotective effect of ERCC1 polymorphisms. Pharmacogenomics. 2011. Tzvetkov Mladen V, et al. PubMed
Genetically Polymorphic OCT1: Another Piece in the Puzzle of the Variable Pharmacokinetics and Pharmacodynamics of the Opioidergic Drug Tramadol. Clinical pharmacology and therapeutics. 2011. Tzvetkov M V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. Journal of medicinal chemistry. 2011. Kido Yasuto, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Rifampin enhances the glucose-lowering effect of metformin and increases OCT1 mRNA levels in healthy participants. Clinical pharmacology and therapeutics. 2011. Cho S K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
OCT-1 as a Determinant of Response to Antileukemic Treatment. Clinical pharmacology and therapeutics. 2011. Engler J R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Global patterns of genetic diversity and signals of natural selection for human ADME genes. Human molecular genetics. 2011. Li Jing, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
OCT1 polymorphism is associated with response and survival time in anti-Parkinsonian drug users. Neurogenetics. 2011. Becker Matthijs L, et al. PubMed
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Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism. 2010. Gambineri Alessandra, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms in organic cation transporter 1 (OCT1) in Chinese and Japanese populations exhibit altered function. The Journal of pharmacology and experimental therapeutics. 2010. Chen Ligong, et al. PubMed
Effects of OCT1 polymorphisms on the cellular uptake, plasma concentrations and efficacy of the 5-HT(3) antagonists tropisetron and ondansetron. The pharmacogenomics journal. 2010. Tzvetkov M V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Membrane interactions of novicidin, a novel antimicrobial peptide: phosphatidylglycerol promotes bilayer insertion. The journal of physical chemistry. B. 2010. Dorosz Jerzy, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug transporter pharmacogenetics in nucleoside-based therapies. Pharmacogenomics. 2010. Errasti-Murugarren Ekaitz, et al. PubMed
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Genotype-dependent effects of inhibitors of the organic cation transporter, OCT1: predictions of metformin interactions. The pharmacogenomics journal. 2010. Ahlin G, et al. PubMed
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Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue. Molecular cancer therapeutics. 2010. More Swati S, et al. PubMed
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Pharmacogenomics of membrane transporters: past, present and future. Pharmacogenomics. 2010. Yee Sook Wah, et al. PubMed
Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenetics and genomics. 2010. Becker Matthijs L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Current understanding of the pharmacogenomics of metformin. Clinical pharmacology and therapeutics. 2009. Zolk O. PubMed
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The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clinical pharmacology and therapeutics. 2009. Tzvetkov M V, et al. PubMed
Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. The pharmacogenomics journal. 2009. Becker M L, et al. PubMed
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Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Kim Dong Hwan Dennis, et al. PubMed
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Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation. PloS one. 2009. Hesselson Stephanie E, et al. PubMed
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Pharmacogenetics of antiretroviral agents. Current opinion in HIV and AIDS. 2008. Owen Andrew, et al. PubMed
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Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leukemia & lymphoma. 2008. Clark Richard E, et al. PubMed
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Polymorphism in human organic cation transporters and metformin action. Pharmacogenomics. 2008. Takane Hiroshi, et al. PubMed
Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clinical pharmacology and therapeutics. 2008. Shu Y, et al. PubMed
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Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia. Clinical pharmacology and therapeutics. 2008. Wang L, et al. PubMed
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Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. The Journal of clinical investigation. 2007. Shu Yan, et al. PubMed
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Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin. Journal of human genetics. 2007. Shikata Eriko, et al. PubMed
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Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer research. 2006. Zhang Shuzhong, et al. PubMed
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The human organic cation transporter-1 gene is transactivated by hepatocyte nuclear factor-4alpha. The Journal of pharmacology and experimental therapeutics. 2006. Saborowski Michael, et al. PubMed
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Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). The Journal of pharmacology and experimental therapeutics. 2004. Jonker Johan W, et al. PubMed
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Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1. Proceedings of the National Academy of Sciences of the United States of America. 2003. Shu Yan, et al. PubMed

LinkOuts

Entrez Gene:
6580
OMIM:
602607
UCSC Genome Browser:
NM_003057
RefSeq RNA:
NM_003057
NM_153187
RefSeq Protein:
NP_003048
NP_694857
RefSeq DNA:
AC_000049
AC_000138
NC_000006
NT_025741
NW_001838991
NW_923184
HuGE:
SLC22A1
Comparative Toxicogenomics Database:
6580
ModBase:
O15245
HumanCyc Gene:
HS10865
HGNC:
10963

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