Affinage

SLC22A3

Solute carrier family 22 member 3 · UniProt O75751

Length
556 aa
Mass
61.3 kDa
Annotated
2026-06-10
58 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC22A3 (OCT3) is a polyspecific, electrogenic organic cation transporter that mediates facilitated uptake of monoamines and cationic drugs across plasma membranes in heart, liver, placenta, skeletal muscle, and the nervous system, and constitutes the principal extraneuronal uptake-2 system of the adult heart (PMID:11390648, PMID:16141367). Its substrate spectrum—distinct from the related OCT1/OCT2 transporters with which it clusters on chromosome 6q26-q27—includes MPP+, histamine, serotonin, the cytotoxic platinum drug oxaliplatin, and metformin, the last of which it carries into target tissues to drive AMPK activation (PMID:9933568, PMID:16141367, PMID:18710896, PMID:19591196, PMID:20859243). In the placenta OCT3 resides on the fetus-facing (basolateral) membrane of the trophoblast and operates as the uptake arm of a vectorial elimination axis with the apical efflux transporter MATE1, clearing organic cations and serotonin from the fetal circulation; co-expression with the monoamine-metabolizing enzyme MAO-A makes this a combined detoxification and serotonin-homeostasis system (PMID:11118898, PMID:22543277, PMID:23562376, PMID:32311818). The gene is subject to genomic imprinting with paternal-allele silencing in placenta, maintained in cis independently of Igf2r/Air transcriptional overlap (PMID:12853484). In the brain, activity-induced astrocytic SLC22A3 imports serotonin to fuel histone serotonylation, GABA biosynthesis, and sensory processing, while cardiac OCT3 loss elevates histamine to drive H1R/NLRP3-dependent neuroinflammation and cognitive impairment (PMID:37319217, PMID:41833108). In epithelial cancers SLC22A3 functions as a metastasis suppressor by binding α-actinin-4 (ACTN4) to restrain its actin-binding and invasive activity, and is silenced through promoter hypermethylation, PITX2-mediated repression, and an AR-V7/YAP1/TAZ–DNMT1 axis (PMID:28533408, PMID:30742940, PMID:36254631, PMID:22730461). Coding and promoter variants of SLC22A3 alter transport kinetics, transcription-factor binding, and downstream drug response and tissue phenotypes (PMID:20859243, PMID:20562519, PMID:22231567, PMID:33168399).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 Medium

    Establishing the gene's identity, chromosomal location, and tissue distribution defined SLC22A3 as a third member of an organic-cation transporter cluster with broad somatic expression.

    Evidence cDNA cloning, Northern blot, and somatic-cell-hybrid/YAC mapping

    PMID:9933568

    Open questions at the time
    • No transport function demonstrated in this study
    • Subcellular localization not resolved
  2. 2001 High

    Knockout of the mouse ortholog answered whether OCT3 carries a defined physiological transport burden in vivo, identifying it as the principal extraneuronal uptake-2 system of the heart and a fetoplacental transporter.

    Evidence Homologous-recombination knockout mouse with in vivo [3H]MPP+ accumulation assays; placental ISH co-localization with Maoa

    PMID:11118898 PMID:11390648

    Open questions at the time
    • Endogenous physiological substrate(s) in heart not pinned to a single monoamine
    • Mechanism of membrane targeting not addressed
  3. 2003 High

    Genetic epistasis defined the cis-regulatory logic of SLC22A3 imprinting, showing paternal silencing does not require Igf2r/Air transcriptional overlap.

    Evidence Knock-in mice with replaced or deleted Igf2r promoter and allele-specific expression analysis

    PMID:12853484

    Open questions at the time
    • The Air-dependent silencing mechanism (chromatin vs. RNA-mediated) not fully resolved
    • Does not address human imprinting status
  4. 2008 High

    Substrate-selectivity and drug-transport studies established OCT3 as a distinct organic-cation carrier handling specific therapeutics including oxaliplatin and famotidine.

    Evidence Xenopus oocyte uptake/electrophysiology and cancer-cell transfection with ICP-MS platinum accumulation and cytotoxicity assays

    PMID:16141367 PMID:18710896

    Open questions at the time
    • Structural basis of substrate selectivity not determined
    • In vivo relevance of oxaliplatin transport not tested
  5. 2010 High

    Linking OCT3 to metformin action and characterizing coding variants connected transport activity to pharmacological outcome and inter-individual variation.

    Evidence shRNA knockdown, pharmacologic inhibition, isotopic uptake, AMPK assays, and variant uptake assays with localization controls

    PMID:19591196 PMID:20562519 PMID:20859243

    Open questions at the time
    • Whether variants alter clinical metformin response not established
    • Hepatic basolateral targeting mechanism unknown
  6. 2012 High

    Dual perfusion of placenta and identification of neuronal/cancer regulators showed OCT3 forms a vectorial transplacental elimination axis with MATE1 and is transcriptionally controlled in specialized cell types.

    Evidence Dually perfused rat placenta with pharmacologic dissection; Pet-1 knockout microarray/ISH in 5-HT neurons; promoter reporter/EMSA/methylation analyses; prostate cancer siRNA phenotyping

    PMID:22231567 PMID:22543277 PMID:22730461 PMID:25642596

    Open questions at the time
    • Whether placental coupling operates identically in human in vivo not fully proven
    • Direct transcription factors driving promoter haplotype effects not all identified
  7. 2013 High

    Demonstration that OCT3 carries metformin fetal-to-maternal against gradient confirmed functional coupling of basolateral OCT3 uptake with apical MATE1 efflux.

    Evidence Dually perfused rat placenta with MPP+ inhibition and pH-gradient manipulation

    PMID:23562376

    Open questions at the time
    • Quantitative contribution to human fetal drug exposure unmeasured
  8. 2017 High

    Identification of the SLC22A3–ACTN4 interaction provided a transport-independent mechanism for its metastasis-suppressor function.

    Evidence Co-IP, actin-binding and invasion/filopodia assays, RNA-editing quantification, and shRNA knockdown in esophageal cancer

    PMID:28533408

    Open questions at the time
    • Whether ACTN4 binding requires transport activity unresolved
    • Structural details of the interaction not defined
  9. 2019 High

    PITX2 was defined as a direct transcriptional repressor of SLC22A3 governing chemoresistance.

    Evidence ChIP-qPCR, bidirectional siRNA/overexpression, and drug-resistance/transporter-activity assays in colon and renal cancer cells

    PMID:30742940

    Open questions at the time
    • Cofactors recruited by PITX2 at the promoter not identified
    • Relationship to methylation-based silencing not integrated
  10. 2020 High

    Placental serotonin-clearance and skin-phenotype studies extended OCT3's physiological roles to fetal serotonin homeostasis and sebaceous gland function, with promoter p53 binding as a regulatory input.

    Evidence Dually perfused rat placenta and human membrane vesicles with pharmacologic inhibition; promoter ChIP/EMSA/reporter and in vivo squalene measurement

    PMID:32311818 PMID:33168399

    Open questions at the time
    • Causal link between OCT3 serotonin uptake and placental vascular outcomes not directly demonstrated in human pregnancy
    • Skin phenotype based on variant correlation
  11. 2022 Medium

    Comparative imprinting and additional cancer-silencing studies showed the imprinting mechanism differs across mammals and that an AR-V7/YAP1/TAZ–DNMT1 axis methylates SLC22A3 in resistant prostate cancer.

    Evidence Marsupial allele-specific expression/bisulfite/localization; Co-IP, siRNA, and promoter methylation analysis in enzalutamide-resistant prostate cancer cells

    PMID:36030241 PMID:36254631

    Open questions at the time
    • Marsupial silencing mechanism without promoter DMR not mechanistically defined
    • AR-V7/YAP1/TAZ–DNMT1 model rests on single-lab Co-IP
  12. 2023 High

    Astrocytic conditional knockout connected OCT3 serotonin import to histone serotonylation and GABAergic signaling, establishing a role in sensory circuit function.

    Evidence Activity-inducible profiling, conditional KO with behavioral phenotyping, serotonin/serotonylation and GABA-release measurements in olfactory bulb

    PMID:37319217

    Open questions at the time
    • Whether this pathway operates in human brain unknown
    • Generality beyond olfactory circuitry untested
  13. 2026 Medium

    Cardiac and cancer-stem-cell studies tied OCT3 substrate transport to histamine-driven neuroinflammation and serotonin-dependent stemness via histone modifications.

    Evidence Mouse MI model with cardiac OCT3 overexpression and hippocampal H1R knockdown/NLRP3 KO; siRNA silencing in 2D and 3D pancreatic cancer organoid models with histone-modification readouts

    PMID:41833108 PMID:42250222

    Open questions at the time
    • Heart-to-brain histamine axis demonstrated only in mouse
    • Direct histone-modification enzymology downstream of OCT3 transport not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OCT3's transport activity is mechanistically coupled to its non-transport scaffolding/suppressor roles, and how a single transporter's substrate flux is translated into chromatin (serotonylation, histone-modification) outputs across tissues, remains unresolved.
  • No structure of human OCT3 reported in the corpus
  • Mechanism linking cation uptake to histone serotonylation enzymology undefined
  • Whether ACTN4 binding and transport are separable functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0140104 molecular carrier activity 3 GO:0008092 cytoskeletal protein binding 1 GO:0016209 antioxidant activity 1
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-382551 Transport of small molecules 5 R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 2
Partners
ACTN4MATEINTERACTIONSLC47A1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Genetic knockout of mouse Orct3/Slc22a3 demonstrated that this transporter is the principal component of the extraneuronal uptake-2 system in the adult heart, as measured by a 72% reduction in intravenously administered [3H]MPP+ accumulation in hearts of null mice. Additionally, Orct3 was identified as functioning at the fetoplacental interface, with a threefold-reduced MPP+ accumulation in homozygous mutant embryos but not in placentas. Homologous recombination knockout mouse model; isotopic [3H]MPP+ uptake assays in vivo Molecular and cellular biology High 11390648
1999 SLC22A3 was cloned and mapped to human chromosome 6q26-q27 in a conserved cluster with SLC22A1 and SLC22A2. Expression was detected in placenta (first-trimester and term), skeletal muscle, prostate, aorta, liver, fetal lung, salivary gland, and adrenal gland. cDNA cloning from EST clones; Northern blot expression analysis; somatic cell hybrid panel mapping; YAC clone mapping Genomics Medium 9933568
2001 Slc22a3/Orct3 co-localizes with the monoamine-metabolizing enzyme Maoa in the labyrinth layer of mouse placenta, establishing that these two components of monoamine clearance are co-expressed at the same site, distinct from neuronal transporter expression patterns. RNA blot analysis; in situ hybridization in mouse embryo placenta sections Mechanisms of development Medium 11118898
2003 Imprinted silencing of Slc22a3 (paternal allele) does not require transcriptional overlap between Igf2r and the non-coding Air RNA; silencing is maintained even when the Igf2r promoter is replaced by a heterologous promoter or deleted entirely. Genetic epistasis using knock-in mice with replaced or deleted Igf2r promoter; allele-specific expression analysis The EMBO journal High 12853484
2005 hOCT3 (SLC22A3) mediates uptake of organic cations with substrate selectivity distinct from hOCT1 and hOCT2: famotidine is a potent inhibitor of hOCT3 (IC50 = 6.7 µM) while ranitidine is a weak inhibitor (IC50 = 290 µM); no stimulation of [3H]ranitidine uptake was detected in hOCT3-expressing oocytes, indicating ranitidine is not an hOCT3 substrate. Xenopus laevis oocyte expression system; isotopic uptake inhibition assays; trans-stimulation; electrophysiology The Journal of pharmacology and experimental therapeutics High 16141367
2008 hOCT3/SLC22A3 transports oxaliplatin (but not cisplatin) into colorectal cancer cells, mediating cytotoxicity: transfection of hOCT3 into SW480 cells increased platinum accumulation and LDH release after oxaliplatin treatment; colorectal cancer cell lines with high endogenous hOCT3 accumulated more platinum and showed greater cytotoxicity. cDNA transfection; LDH release cytotoxicity assay; ICP-MS platinum accumulation measurement; qRT-PCR mRNA quantification Drug metabolism and disposition High 18710896
2009 OCT3/SLC22A3 protein is localized to the basolateral membrane of hepatocytes, and metformin is confirmed as an OCT3 substrate by isotopic uptake studies in transfected cells. Immunofluorescence microscopy for subcellular localization; isotopic uptake assays in transfected cells Hepatology Medium 19591196
2010 OCT3/SLC22A3 plays a role in metformin's pharmacological action: OCT3 is expressed on the plasma membrane of skeletal muscle and liver (metformin target tissues); OCT inhibitor cimetidine and OCT3-specific shRNA significantly reduced metformin-induced AMP-activated protein kinase activation. Three missense variants (T44M, T400I, V423F) showed altered substrate specificity for metformin and catecholamines in functional assays. Quantitative PCR; immunostaining; isotopic uptake assays in transfected cells; shRNA knockdown; AMPK phosphorylation assay; structural modeling Pharmacogenetics and genomics High 20859243
2010 Three OCT3 missense variants (A116S, T400I, A439V) show reduced uptake of both [3H]histamine and [3H]MPP+ despite normal plasma membrane localization, indicating these variants impair transport activity without affecting trafficking. Transient transfection; isotopic uptake assays; immunostaining for protein localization Journal of pharmacological sciences Medium 20562519
2012 The SLC22A3 promoter is regulated by epigenetic methylation (associated with reduced expression in prostate cancer) and by genetic variants: haplotypes containing g.-81G>delGA and g.-2G>A show increased luciferase reporter activity and stronger transcription factor binding affinity; the g.-2A allele correlates with higher OCT3 mRNA in liver. Luciferase reporter assay; electrophoretic mobility shift assay; bisulfite sequencing; mRNA expression analysis in human liver samples The pharmacogenomics journal Medium 22231567
2012 Oct3/Slc22a3 is localized on the basolateral (fetus-facing) side of rat placental trophoblast, and together with apically-localized Mate1/Slc47a1, forms an efficient transplacental eliminatory pathway: Oct3 takes up MPP+ from fetal circulation into the placenta, while Mate1 effluxes it to the maternal side, transporting substrate against a concentration gradient. qRT-PCR; Western blot; immunohistochemistry; in situ dually perfused rat term placenta (open- and closed-circuit); [3H]MPP+ transport assays Toxicological sciences High 22543277
2013 OCT3/SLC22A3 mediates the fetal-to-maternal transplacental transfer of metformin in rat placenta in a concentration-dependent manner; this transport is completely inhibited by MPP+ and is driven by opposing H+ gradient for MATE1-mediated efflux, confirming functional coupling of OCT3 (basolateral uptake) and MATE1 (apical efflux) in metformin secretion. Dually perfused rat term placenta model; pharmacologic inhibition with MPP+; pH gradient manipulation Reproductive toxicology High 23562376
2015 The transcription factor Pet-1 controls expression of Slc22a3 in serotonin neurons: comparative microarray profiling of flow-sorted Pet-1-/- versus wild-type 5-HT neurons showed loss of Slc22a3 expression; in situ hybridization confirmed that virtually all 5-HT neurons in the dorsal raphe depend on Pet-1 for Slc22a3 expression, establishing Pet-1 as a transcriptional regulator coordinating both 5-HT synthesis and reuptake genes. Comparative microarray of flow-sorted YFP+ neurons; in situ hybridization ACS chemical neuroscience Medium 25642596
2017 A-to-I RNA editing of SLC22A3 mRNA by ADAR2 results in reduced SLC22A3 expression in non-tumor esophageal tissues. SLC22A3 acts as a metastasis suppressor: it directly associates with α-actinin-4 (ACTN4), and loss of this interaction increases ACTN4 actin-binding activity, facilitating cell invasion and filopodia formation. Co-immunoprecipitation (SLC22A3–ACTN4 interaction); actin-binding activity assay; cell invasion assays; filopodia formation imaging; RNA editing quantification; shRNA knockdown Proceedings of the National Academy of Sciences of the United States of America High 28533408
2019 Oncogenic PITX2 transcription factor represses SLC22A3/hOCT3 expression: ChIP-qPCR showed PITX2 binds the hOCT3/SLC22A3 promoter in colon and renal cancer cells; PITX2 siRNA knockdown increased hOCT3/SLC22A3 expression and activity and reverted vincristine resistance, while heterologous PITX2 overexpression suppressed hOCT3/SLC22A3 and enhanced drug resistance. PITX2A and PITX2C isoforms were most effective. ChIP-qPCR; siRNA knockdown; heterologous overexpression; drug resistance/viability assays; transporter activity assays Cancer letters High 30742940
2020 OCT3/SLC22A3 is localized on the fetus-facing membrane of syncytiotrophoblast in human and rat term placenta, where it massively takes up serotonin from fetal circulation in a concentration-dependent and OCT3 blocker-inhibitable manner, forming a protective mechanism against local vasoconstriction with MAO-A. Glucocorticoids and antidepressants can inhibit this system. Dually perfused rat term placenta; placental membrane vesicles from human term placenta; pharmacologic inhibition with OCT3 blockers (glucocorticoids, pharmaceuticals); concentration-response analysis Acta physiologica High 32311818
2020 The SLC22A3 promoter variant -1603G>A reduces p53 binding to the promoter region, leading to decreased SLC22A3 mRNA expression in human skin; homozygous -1603A/A individuals have significantly lower SLC22A3 mRNA levels and lower squalene levels in skin, linking OCT3 to sebaceous gland function. Immunohistochemistry; luciferase reporter assay; ChIP; electrophoretic mobility shift assay (EMSA); mRNA expression analysis; in vivo sebum/squalene measurement Journal of dermatological science Medium 33168399
2022 AR-V7/YAP1/TAZ axis represses SLC22A3 in enzalutamide-resistant castration-resistant prostate cancer: YAP1/TAZ hyperactivated by AR full-length or AR-V7 interacts with DNMT1 to methylate and silence the SLC22A3 promoter; this repression was demonstrated in ENZ-resistant C4-2B MDVR cells. Co-immunoprecipitation (YAP1/TAZ–DNMT1 interaction); siRNA knockdown; promoter methylation analysis; Western blot; immunostaining in patient tissues The FEBS journal Medium 36254631
2023 Neuronal activity induces Slc22a3 expression in astrocytes; loss of astrocytic Slc22a3 reduces intracellular serotonin levels, leading to decreased histone serotonylation in astrocytes, reduced GABA biosynthetic gene expression, reduced GABA release, and olfactory sensory processing deficits in mice. Activity-inducible gene expression profiling; conditional knockout (loss-of-function) with behavioral phenotyping; serotonin quantification; histone serotonylation assay; GABA release measurement; olfactory bulb circuit analysis Science High 37319217
2022 Tammar wallaby SLC22A3 is imprinted (paternal allele silenced) specifically in placental tissue, with the protein localized to the endodermal cell layer where nutrient trafficking occurs; promoter lacks DNA methylation, indicating silencing is not via direct DMR at the SLC22A3 promoter as in mouse. Allele-specific expression analysis; bisulfite sequencing; immunofluorescence localization in tammar wallaby placenta Epigenetics & chromatin Medium 36030241
2012 SLC22A3 suppression reduces tumor-related cellular phenotypes (proliferation, migration, invasion) in prostate cancer cells, implicating SLC22A3 in prostate cancer pathogenesis through functional cellular assays. siRNA knockdown of SLC22A3 in prostate cancer cell lines; assays for proliferation, migration, and invasion Proceedings of the National Academy of Sciences of the United States of America Medium 22730461
2018 SLC22A3 acts as an antioxidant gene in normal esophageal epithelial cells: deregulation of SLC22A3 (by promoter hypermethylation) facilitates heat stress-induced oxidative DNA damage and formation of γ-H2AX foci. Bisulfite sequencing for promoter methylation; γ-H2AX foci immunofluorescence after heat stress; functional overexpression/knockdown International journal of biological sciences Medium 30416380
2026 SLC22A3/OCT3 regulates pancreatic cancer stem cell (CSC) stemness through serotonin transport: SLC22A3 is upregulated in CSC-enriched populations; its silencing in 2D cultures and 3D organoid models reduces stemness features; serotonin transport by SLC22A3 enhances stemness via downstream histone modifications. siRNA silencing; 2D cell culture and 3D organoid models; stemness assays; histone modification analysis Cell reports Medium 42250222
2026 Cardiac SLC22A3 deficiency in heart failure leads to elevated peripheral and brain histamine levels; cardiac-specific SLC22A3 overexpression reduces histamine accumulation, preserves blood-brain barrier integrity, and improves cognitive performance. Mechanistically, elevated histamine activates hippocampal microglial H1R/NLRP3 inflammasome signaling to drive neuroinflammation; blocking H1R or NLRP3 in hippocampus rescues heart failure-induced cognitive impairment. Mouse MI model; cardiac-specific SLC22A3 overexpression; hippocampal-specific H1R knockdown; NLRP3 knockout mice; BV2 cell assays; Morris water maze; immunofluorescence; Western blot Redox biology Medium 41833108

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nature genetics 362 19198611
2009 Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology (Baltimore, Md.) 308 19591196
2010 Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin. Pharmacogenetics and genomics 162 20859243
2001 Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice. Molecular and cellular biology 147 11390648
1999 Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a conserved cluster of three organic cation transporters on mouse chromosome 17 and human 6q26-q27. Genomics 96 9933568
2012 Genetic and functional analyses implicate the NUDT11, HNF1B, and SLC22A3 genes in prostate cancer pathogenesis. Proceedings of the National Academy of Sciences of the United States of America 90 22730461
2017 RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer. Proceedings of the National Academy of Sciences of the United States of America 85 28533408
2005 Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). The Journal of pharmacology and experimental therapeutics 83 16141367
2008 Significance of organic cation transporter 3 (SLC22A3) expression for the cytotoxic effect of oxaliplatin in colorectal cancer. Drug metabolism and disposition: the biological fate of chemicals 82 18710896
2003 Imprinted silencing of Slc22a2 and Slc22a3 does not need transcriptional overlap between Igf2r and Air. The EMBO journal 73 12853484
2012 Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3. The pharmacogenomics journal 68 22231567
2020 Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta. Acta physiologica (Oxford, England) 65 32311818
2023 Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation. Science (New York, N.Y.) 63 37319217
2006 Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder. Alcoholism, clinical and experimental research 42 17010131
2010 Functional analysis of human organic cation transporter OCT3 (SLC22A3) polymorphisms. Journal of pharmacological sciences 38 20562519
2001 The extraneuronal monoamine transporter Slc22a3/Orct3 co-localizes with the Maoa metabolizing enzyme in mouse placenta. Mechanisms of development 34 11118898
2019 Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels. Journal of personalized medicine 32 30934600
2012 Synchronized activity of organic cation transporter 3 (Oct3/Slc22a3) and multidrug and toxin extrusion 1 (Mate1/Slc47a1) transporter in transplacental passage of MPP+ in rat. Toxicological sciences : an official journal of the Society of Toxicology 32 22543277
2013 Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein. Reproductive toxicology (Elmsford, N.Y.) 31 23562376
2016 Functional Variant in the SLC22A3-LPAL2-LPA Gene Cluster Contributes to the Severity of Coronary Artery Disease. Arteriosclerosis, thrombosis, and vascular biology 30 27417586
2013 Human organic cation transporters 1 (SLC22A1), 2 (SLC22A2), and 3 (SLC22A3) as disposition pathways for fluoroquinolone antimicrobials. Antimicrobial agents and chemotherapy 29 23545524
2019 Oncogenic PITX2 facilitates tumor cell drug resistance by inverse regulation of hOCT3/SLC22A3 and ABC drug transporters in colon and kidney cancers. Cancer letters 27 30742940
2019 Genetic variants in SLC22A3 contribute to the susceptibility to colorectal cancer. International journal of cancer 25 30561001
2003 Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3). Journal of human genetics 22 12768439
2018 Epigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer. International journal of biological sciences 21 30416380
2017 Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment. Oncotarget 20 29088791
2012 Renal tumours in a Tsc1+/- mouse model show epigenetic suppression of organic cation transporters Slc22a1, Slc22a2 and Slc22a3, and do not respond to metformin. European journal of cancer (Oxford, England : 1990) 20 23228442
2019 SLC22A3 is associated with lipoprotein (a) concentration and cardiovascular disease in familial hypercholesterolemia. Clinical biochemistry 19 30772277
2015 Pet-1 Controls Tetrahydrobiopterin Pathway and Slc22a3 Transporter Genes in Serotonin Neurons. ACS chemical neuroscience 17 25642596
2000 Analysis of the gene structure of the human (SLC22A3) and murine (Slc22a3) extraneuronal monoamine transporter. Journal of neural transmission (Vienna, Austria : 1996) 15 11129104
2018 Evaluation of the rs3088442 G>A SLC22A3 Gene Polymorphism and the Role of microRNA 147 in Groups of Adult Pakistani Populations With Type 2 Diabetes in Response to Metformin. Canadian journal of diabetes 14 30297296
2017 SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. Scientific reports 14 28272475
2012 Lack of association between four SNPs in the SLC22A3-LPAL2-LPA gene cluster and coronary artery disease in a Chinese Han population: a case control study. Lipids in health and disease 14 23036009
2017 PHACTR1 and SLC22A3 gene polymorphisms are associated with reduced coronary artery disease risk in the male Chinese Han population. Oncotarget 12 27893421
2016 Allele frequency and genotype distribution of a common variant in the 3´-untranslated region of the SLC22A3 gene in patients with type 2 diabetes: Association with response to metformin. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 10 28163738
2021 Effect of SYTL3-SLC22A3 Variants, Their Haplotypes, and G × E Interactions on Serum Lipid Levels and the Risk of Coronary Artery Disease and Ischaemic Stroke. Frontiers in cardiovascular medicine 9 34458338
2001 Genetic analysis of the organic cation transporter genes Orct2/Slc22a2 and Orct3/Slc22a3 reduces the critical region for the t haplotype mutant t(w73) to 200 kb. Mammalian genome : official journal of the International Mammalian Genome Society 9 11641723
2022 Placental imprinting of SLC22A3 in the IGF2R imprinted domain is conserved in therian mammals. Epigenetics & chromatin 8 36030241
2022 The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic efficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study. Gene 7 35240257
2021 SYTL3-SLC22A3 Single-Nucleotide Polymorphisms and Gene-Gene/Environment Interactions on the Risk of Hyperlipidemia. Frontiers in genetics 7 34367243
2017 Oesophageal cancer: RNA editing of SLC22A3 mRNAs: causative relevance to familial ESCC? Nature reviews. Gastroenterology & hepatology 6 28743982
2023 SLC22A3 rs2048327 Polymorphism Is Associated with Diabetic Retinopathy in Caucasians with Type 2 Diabetes Mellitus. Biomedicines 5 37626799
2022 Repression of SLC22A3 by the AR-V7/YAP1/TAZ axis in enzalutamide-resistant castration-resistant prostate cancer. The FEBS journal 5 36254631
2025 Molecular Ancestry Across Allelic Variants of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Mexican-Mestizo DMT2 Patients. Biomedicines 4 40426982
2023 Effect of MEF2A and SLC22A3-LPAL2-LPA gene polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients. PloS one 4 37948393
2022 A Single Nucleotide Polymorphism (SNP) in the SLC22A3 Transporter Gene Is Associated With the Severity of Oral Mucositis in Multiple Myeloma Patients Receiving Autologous Stem Cell Transplant Followed by Melphalan Therapy. Anticancer research 4 34969749
2023 The Influence of SLC22A3 Genetic Polymorphisms on Susceptibility to Type 2 Diabetes Mellitus in Chinese Population. Diabetes, metabolic syndrome and obesity : targets and therapy 2 37342315
2020 Effect of Genetic Polymorphisms of Human SLC22A3 in the 5'-flanking Region on OCT3 Expression and Sebum Levels in Human Skin. Journal of dermatological science 2 33168399
2016 A Case-Control Study of the Relationship Between SLC22A3-LPAL2-LPA Gene Cluster Polymorphism and Coronary Artery Disease in the Han Chinese Population. Iranian Red Crescent medical journal 2 27621937
2024 A Polynesian-specific SLC22A3 variant associates with low plasma lipoprotein(a) concentrations independent of apo(a) isoform size in males. Bioscience reports 1 38896441
2023 Activity-dependent induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation. bioRxiv : the preprint server for biology 1 36909526
2012 [Association of prostate cancer with PDLIM5, SLC22A3 and NKX3-1 in Chinese men]. Zhonghua nan ke xue = National journal of andrology 1 22741436
2026 Comprehensive Analysis of Bulk RNA-seq, Machine Learning, Mendelian Randomization, and Single-Cell Sequencing Unravels SLC22A3 as a Solute Carrier Superfamily-Associated Biomarker in Atherosclerosis. Journal of cardiovascular translational research 0 41806154
2026 SLC22A3 deficiency leads to cognitive impairment through the cardio-neuroinflammatory axis mediated HA/H1R/NLRP3 pathway in heart failure mice. Redox biology 0 41833108
2026 SLC22A3/OCT3 drives serotonin-mediated stemness in pancreatic cancer. Cell reports 0 42250222
2025 Unraveling the protective role of m6A methylation in SLC22A3 expression for breast Cancer intervention. Biochimica et biophysica acta. Molecular basis of disease 0 40570980
2025 Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus. Pharmaceuticals (Basel, Switzerland) 0 41011206
2023 Genetic preservation of SLC22A3 in the Admixed and Xhosa populations living in the Western Cape. Molecular biology reports 0 37924453

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