SLC22A8
Solute Carrier Family 22 Member 8 (OAT3)
Gene Information Card
| Symbol | SLC22A8 |
|---|---|
| Full Name | Solute Carrier Family 22 Member 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q12.3 |
| NCBI Gene ID | 9376 ncbi.nlm.nih.gov/gene/9376 |
| Ensembl ID | ENSG00000149476 |
| UniProt ID | Q8N695 |
| OMIM ID | 607581 |
| HGNC ID | 10971 |
| Aliases | OAT3, hOAT3, OATP3, PAHT |
Description
SLC22A8 encodes the organic anion transporter 3 (OAT3), a membrane protein primarily expressed in the basolateral membrane of renal proximal tubule cells. OAT3 mediates the uptake of a wide range of endogenous and exogenous organic anions, including drugs (e.g., methotrexate, NSAIDs, diuretics), toxins, and metabolites, facilitating their renal secretion and clearance. It plays a key role in pharmacokinetics and drug-drug interactions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic Kidney Disease | Reduced OAT3 expression/activity impairs renal clearance of uremic toxins, contributing to toxin accumulation | PMID: 25687188 |
| Drug-Induced Nephrotoxicity | Polymorphisms in SLC22A8 alter transporter activity, affecting drug accumulation and toxicity risk | PMID: 23588300 |
| Hyperuricemia | OAT3 mediates urate transport; variants may influence urate excretion and gout risk | PMID: 23263487 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 102.3 | High |
| Liver | 12.1 | Medium |
| Brain | 5.4 | Low |
| Placenta | 3.8 | Low |
| Skeletal Muscle | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HK-2 (kidney proximal tubule) | 85.6 | High expression; model for renal transport studies |
| HepG2 (liver) | 9.2 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.149G>A (p.Arg50His) | Missense | 0.2% (gnomAD) | Reduced transport activity for estrone sulfate |
| c.602C>T (p.Pro201Leu) | Missense | 0.1% (gnomAD) | Decreased methotrexate uptake |
| c.1196G>A (p.Arg399Gln) | Missense | 0.5% (gnomAD) | Altered substrate specificity |
Mutation functional classification
Loss of Function (LOF)
p.Arg50His and p.Pro201Leu reduce or abolish transport of organic anions such as estrone sulfate and methotrexate.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in SLC22A8.
Dominant Negative (DN)
Not described for SLC22A8; transporter functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Renal organic anion transport (Reactome: R-HSA-549127)
• Drug metabolism - other enzymes (KEGG: hsa00983)
• Transport of organic anions (WikiPathways: WP3649)
Protein Summary
OAT3 is a 542-amino acid transmembrane protein with 12 predicted alpha-helical domains. It functions as an organic anion/dicarboxylate exchanger, coupling the uptake of organic anions with the efflux of alpha-ketoglutarate. OAT3 is essential for renal secretion of many drugs and endogenous metabolites, and its activity is modulated by phosphorylation and protein-protein interactions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC22A8 Knockout HEK293 Cell Line | EDJ-KQ6565 | Human | 9376 | Details Get a Quote |
| SLC22A8 Knockout HeLa Cell Line | EDJ-KQ55145 | Human | 9376 | Details Get a Quote |
| SLC22A8 Knockout A-549 Cell Line | EDJ-KQ63624 | Human | 9376 | Details Get a Quote |
| SLC22A8 Knockout HCT 116 Cell Line | EDJ-KQ72089 | Human | 9376 | Details Get a Quote |
