SLC22A6 Gene: Organic Anion Transporter 1 (OAT1) - Function, Mutations & Clinical Significance

SLC22A6 encodes organic anion transporter 1 (OAT1), a transmembrane protein primarily expressed in the kidney proximal tubule. OAT1 mediates the uptake of a wide range of organic anions from blood into renal epithelial cells, facilitating their excretion into urine. Substrates include endogenous metabolites (e.g., urate, cyclic nucleotides) and numerous drugs (e.g., NSAIDs, antivirals, diuretics, methotrexate). OAT1 plays a critical role in renal drug clearance, nephrotoxicity, and drug-drug interactions. Genetic variants in SLC22A6 can alter transporter function and impact drug disposition and toxicity risk.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Renal organic anion transport (Reactome: R-HSA-549127)

• Transport of organic anions (KEGG: hsa04976)

• Drug metabolism - other enzymes (KEGG: hsa00983)

Organic anion transporter 1 (OAT1) is a 550-amino acid integral membrane protein with 12 transmembrane domains. It functions as an organic anion/dicarboxylate exchanger, coupling the uptake of organic anions to the efflux of α-ketoglutarate. OAT1 is localized to the basolateral membrane of renal proximal tubule cells. Its structure includes a large extracellular loop between transmembrane domains 1 and 2, and intracellular N- and C-termini. Post-translational modifications include N-glycosylation at Asn39 and Asn113, which are essential for proper trafficking and function. OAT1 interacts with PDZ domain-containing proteins (e.g., PDZK1) for membrane anchoring.