SLC22A3 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 22 (organic cation transporter), member 3
Description	Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC22A3, which encodes organic cation transporter 3 (OCT3), has emerged as a multifunctional protein implicated in human disease susceptibility. Genome‐wide analyses have identified the SLC22A3-containing gene cluster as a risk locus for coronary artery disease and several cancers—including prostate, colorectal, and esophageal malignancies—where altered expression and genetic variants appear to affect disease onset and progression. In familial esophageal squamous cell carcinoma, for example, A‐to‐I RNA editing and promoter hypermethylation of SLC22A3 have been linked to reduced expression that correlates with enhanced metastasis, while single‐nucleotide polymorphisms in its regulatory regions have been associated with prostate cancer risk and poorer clinical outcomes. Moreover, deletion of the gene cluster in 6q25 has been noted in patients with developmental and speech disorders, suggesting that gene dosage may also influence phenotypic variability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in modulating disease risk, SLC22A3 functions as a key transporter mediating the uptake and efflux of endogenous biogenic amines and cationic drugs. OCT3 is widely expressed in tissues such as the liver, heart, placenta, and lung, where it facilitates the cellular entry and clearance of numerous substrates including metformin, histamine, and even anticancer agents such as cisplatin. Functional studies using recombinant systems have demonstrated that through its substrate specificity and transport kinetics, OCT3 contributes not only to the pharmacokinetics and bioavailability of several medications (with implications for drug response and toxicity) but also plays a role in the disposition of compounds related to neurotransmission and cellular signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and epigenetic modifications of SLC22A3 further modulate its transporter activity and have been implicated in neuropsychiatric and substance use disorders as well as in multidrug resistance phenotypes observed in cancer. For instance, rare coding mutations and regulatory polymorphisms in SLC22A3 have been associated with methamphetamine dependence and obsessive-compulsive disorder, suggesting that reduced or altered transporter function may disturb catecholamine clearance in the central nervous system. In cancer cells, transcriptional repression of SLC22A3—mediated by factors such as PITX2—can diminish drug uptake, thereby facilitating chemoresistance. Together, these findings underscore the critical role of SLC22A3 in cellular homeostasis, drug response, and disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David-Alexandre Trégouët, Inke R König, Jeanette Erdmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.314"}], "href": "https://doi.org/10.1038/ng.314"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19198611"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19198611"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kevin M Waters, Loic Le Marchand, Laurence N Kolonel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Generalizability of associations from prostate cancer genome-wide association studies in multiple populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Epidemiol Biomarkers Prev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1055-9965.EPI-08-1142"}], "href": "https://doi.org/10.1158/1055-9965.EPI-08-1142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19318432"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19318432"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chiara Grisanzio, Lillian Werner, David Takeda, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic alterations of a novel antioxidant gene "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SLC22A3"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " predispose susceptible individuals to increased risk of esophageal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.28482"}], "href": "https://doi.org/10.7150/ijbs.28482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30416380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30416380"}]}]}]}
Synonyms	EMTH
Proteins	S22A3_HUMAN
NCBI Gene ID	6581
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC22A3 has 7,131 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for SLC22A3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC22A3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC22A3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC22A3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SLC22A3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SLC22A3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SLC22A3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC22A3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC22A3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC22A3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC22A3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SLC22A3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC22A3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC22A3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with SLC22A3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SLC22A3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC22A3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC22A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SLC22A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SLC22A3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC22A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC22A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SLC22A3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SLC22A3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC22A3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC22A3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SLC22A3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SLC22A3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SLC22A3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SLC22A3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SLC22A3 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SLC22A3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SLC22A3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SLC22A3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SLC22A3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SLC22A3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SLC22A3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SLC22A3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SLC22A3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC22A3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC22A3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SLC22A3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.