Solute carrier family 22 member 6 (SLC22A6) (OAT1)

Solute carrier family 22 member 6 (SLC22A6), commonly known as Organic anion transporter 1 (OAT1), is a multispecific transmembrane protein primarily expressed on the basolateral membrane of renal proximal tubular cells [1.1.1, 1.2.1]. It plays a critical role in the renal handling of a wide variety of endogenous and exogenous organic anions, including metabolic waste products, signaling molecules, and numerous therapeutic drugs [1.1.3, 1.2.1]. OAT1 functions as an exchanger, coupling the uptake of organic anions from the blood into the tubular cells with the efflux of endogenous dicarboxylates like alpha-ketoglutarate [1.2.1, 1.4.1]. In the context of disease, OAT1 is a key player in the regulation of systemic urate levels, and its dysfunction or genetic variation is associated with hyperuricemia and gout [1.4.1, 1.4.4]. Furthermore, OAT1 is a major site for drug-drug interactions and drug-induced nephrotoxicity, as many clinically important medications, such as antivirals (e.g., tenofovir) and antibiotics, are substrates or inhibitors of this transporter [1.1.3, 1.3.4]. Therapeutic modulation of OAT1, for instance by the inhibitor probenecid, is used to prolong the half-life of certain drugs or to protect the kidneys from the accumulation of toxic substrates [1.1.3, 1.3.4].

Other names

Organic anion transporter 1SLC22A6HOAT1PAHTROAT1Novel kidney transporterNKTUrate transporter OAT1

OAT1 functions as an organic anion/dicarboxylate exchanger (antiporter) that facilitates the uptake of organic anions from the peritubular fluid into proximal tubule cells in exchange for intracellular dicarboxylates such as alpha-ketoglutarate [1.2.1, 1.4.1]. This process is driven by the dicarboxylate gradient maintained by sodium-dicarboxylate cotransporters [1.2.1]. Drugs can act as substrates that are transported for excretion or as inhibitors that block the transport of other substances, leading to changes in drug clearance and potential toxicity [1.1.3, 1.3.4].