SLC22A8

Description

The SLC22A8 (solute carrier family 22 member 8) is a protein-coding gene located on chromosome 11.

Solute carrier family 22 member 8, or organic anion transporter 3 (OAT3), is a protein that in humans is encoded by the SLC22A8 gene.

== Function == OAT3 is involved in the transport and excretion of organic ions some of which are drugs (e.g., penicillin G (benzylpenicillin), methotrexate (MTX), indomethacin (an NSAID), and ciprofloxacin (a fluoroquinolone antibiotic)) and some of which are pure toxicants. SLC22A8 (OAT3) is indirectly dependent on the inward sodium gradient, which is a driving force for reentry of dicarboxylates into the cytosol. Dicarboxylates, such as alpha-ketoglutarate generated within the cell, or recycled from the extracellular space, are used as exchange substrates to fuel the influx of organic anions against their concentration gradient. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of renal proximal tubule cells.

SLC22A8, also known as Organic anion transporter 3 (OAT3) or Organic anion/dicarboxylate exchanger, is a protein that functions as an organic anion/dicarboxylate exchanger. This means it transports organic anions, such as estrone 3-sulfate (E1S) and urate, across cell membranes in exchange for dicarboxylates like glutarate or ketoglutarate (2-oxoglutarate). This exchange process is indirectly linked to the sodium gradient, which acts as a driving force. OAT3 plays a crucial role in the excretion of both endogenous and exogenous organic anions, particularly in the kidney and brain. The transport of E1S is influenced by pH and chloride levels and might also involve E1S/cGMP exchange. OAT3 is responsible for transporting prostaglandins E2 and F2(alpha) in the renal tubule's basolateral side. It also transports neuroactive tryptophan metabolites, kynurenate and xanthurenate. OAT3 acts as a biopterin transporter, involved in the uptake and secretion of coenzymes like tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and sepiapterin into urine, influencing blood biopterin levels. OAT3 may also be involved in the basolateral transport of steviol, a metabolite of the stevioside sugar substitute. Additionally, OAT3 participates in detoxification and renal excretion of various drugs and xenobiotics, including histamine H(2)-receptor antagonists (fexofenadine and cimetidine), the antibiotic benzylpenicillin (PCG), the herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA). It contributes to the renal uptake of potent uremic toxins like indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), as well as drugs like pravastatin, PCG, E1S, and dehydroepiandrosterone sulfate (DHEAS). It is also partially involved in the renal uptake of temocaprilat, an angiotensin-converting enzyme (ACE) inhibitor. OAT3 may contribute to cortisol release in the adrenals. It plays a part in the detoxification system on the choroid plexus (CP) by removing substrates like E1S, taurocholate (TC), PCG, 2,4-D, and PAH from the cerebrospinal fluid (CSF) into the blood for ultimate excretion in urine and bile. OAT3 also contributes to the uptake of several other organic compounds including prostanoids (prostaglandin E(2) and prostaglandin F(2-alpha)), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP), and 5-fluorouracil (5-FU). It mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin from the cerebrum into the blood circulation across the blood-brain barrier (BBB). Overall, OAT3 plays a significant role in the efflux of drugs and xenobiotics, which helps to reduce their unwanted toxicological effects on the body.

SLC22A8 is also known as OAT3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing