SLC22A3 (OCT3): Organic Cation Transporter 3 in Drug Disposition and Disease
A comprehensive biomedical overview of the SLC22A3 gene, encoding the polyspecific organic cation transporter OCT3, with emphasis on its role in transport, disease associations, and clinical relevance.
Gene Information Card
| Symbol | SLC22A3 |
|---|---|
| Full Name | solute carrier family 22 member 3 |
| Gene Type | protein coding |
| Chromosomal Location | 6q25.3 |
| NCBI Gene ID | 6581 ncbi.nlm.nih.gov/gene/6581 |
| Ensembl ID | ENSG00000146477 |
| UniProt ID | O75751 |
| OMIM ID | 604842 |
| HGNC ID | 10967 |
| Aliases | OCT3, EMT, OCTN3, SLC22A3 |
Description
SLC22A3 encodes the organic cation transporter 3 (OCT3), a polyspecific transporter belonging to the solute carrier family 22. OCT3 mediates the sodium-independent uptake of various organic cations, including endogenous compounds (e.g., dopamine, histamine) and xenobiotics (e.g., metformin, cisplatin). It is widely expressed in tissues such as liver, kidney, placenta, and brain, and plays a role in drug disposition, neurotransmitter clearance, and cellular homeostasis. Genetic variations in SLC22A3 have been associated with altered drug response and disease susceptibility, including cancer and cardiovascular conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Reduced expression of SLC22A3 may contribute to tumor progression; genetic variants associated with risk. | ClinVar, COSMIC |
| Coronary artery disease | Polymorphisms in SLC22A3 have been linked to altered risk, possibly via effects on catecholamine metabolism. | ClinVar, literature |
| Cisplatin-induced nephrotoxicity | Variants affecting OCT3 transport activity may influence renal accumulation of cisplatin. | ClinVar, literature |
| Metformin response (type 2 diabetes) | SLC22A3 variants can affect hepatic uptake of metformin, altering glycemic response. | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (approx. 30-40 nTPM) | High expression in hepatocytes; involved in hepatic clearance of organic cations. |
| Kidney | Moderate (approx. 15-25 nTPM) | Expressed in renal tubular cells; contributes to renal secretion of cationic drugs. |
| Placenta | High (approx. 50-60 nTPM) | Abundant in trophoblast; may mediate fetal-maternal transfer of compounds. |
| Brain | Low to moderate (approx. 5-10 nTPM) | Present in neurons and glia; involved in neurotransmitter transport. |
| Skeletal muscle | Low (approx. 2-5 nTPM) | Minimal expression; role less defined. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | Approx. 20-30 nTPM | Moderate expression; used in drug transport studies. |
| Caco-2 (colon cancer) | Approx. 5-10 nTPM | Low expression; intestinal absorption model. |
| HK-2 (kidney proximal tubule) | Approx. 15-20 nTPM | Relevant for renal transport studies. |
| SH-SY5Y (neuroblastoma) | Approx. 8-12 nTPM | Neuronal model; OCT3 expression may affect neurotransmitter handling. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs8187715 (c.1199G>A, p.Arg400His) | Missense | Allele frequency ~5-10% in some populations | Reduced transport activity for some substrates; associated with altered drug response. |
| rs12212674 (c.1456C>T, p.Leu486Phe) | Missense | Allele frequency ~2-5% | Potential impact on substrate specificity; clinical significance uncertain. |
| rs2048327 (intronic variant) | Intronic | Common (MAF >20%) | May affect splicing or expression; linked to disease associations in some studies. |
| Copy number loss (partial deletion) | Structural variant | Rare | Loss of function; may contribute to reduced OCT3 expression in tumors. |
Mutation functional classification
Loss of Function (LOF)
Missense variants such as p.Arg400His can reduce transport capacity, leading to decreased cellular uptake of substrates like metformin and cisplatin, potentially affecting drug efficacy and toxicity.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for SLC22A3; most variants are loss-of-function or neutral.
Dominant Negative (DN)
No evidence for dominant-negative effects; SLC22A3 functions as a monomer, and heterozygous loss may not exert dominant effects.
View complete mutation data：
Gene Ontology (GO)
| • transmembrane transport | • organic cation transport |
| • plasma membrane | • integral component of membrane |
| • transport activity | • symporter activity |
Pathways
• Organic cation transport
• Drug metabolism - cytochrome P450
• Metformin pathway
• Catecholamine metabolism
Protein Summary
OCT3 is a 556-amino acid polyspecific transporter with 12 predicted transmembrane domains. It facilitates the bidirectional, sodium-independent transport of organic cations, driven by the electrochemical gradient. OCT3 is characterized by broad substrate specificity, including endogenous amines (dopamine, epinephrine, histamine) and numerous drugs (metformin, cisplatin, oxaliplatin). It is expressed in multiple tissues, with highest levels in placenta, liver, and kidney. OCT3 plays a critical role in hepatic and renal clearance of cationic drugs, and its dysfunction has been implicated in drug-induced toxicity and disease pathogenesis. Post-translational modifications and oligomerization may modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC22A3 Knockout HEK293 Cell Line | EDJ-KQ5797 | Human | 6581 | Details Get a Quote |
| SLC22A31 Knockout HEK293 Cell Line | EDJ-KQ10477 | Human | 146429 | Details Get a Quote |
| SLC22A3 Knockout HeLa Cell Line | EDJ-KQ27951 | Human | 6581 | Details Get a Quote |
| SLC22A3 Knockout A-549 Cell Line | EDJ-KQ29211 | Human | 6581 | Details Get a Quote |
| SLC22A31 Knockout HCT 116 Cell Line | EDJ-KQ36582 | Human | 146429 | Details Get a Quote |
| SLC22A31 Knockout HeLa Cell Line | EDJ-KQ58545 | Human | 146429 | Details Get a Quote |
| SLC22A31 Knockout A-549 Cell Line | EDJ-KQ67035 | Human | 146429 | Details Get a Quote |
| SLC22A3 Knockout HCT 116 Cell Line | EDJ-KQ71476 | Human | 6581 | Details Get a Quote |
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