Solute carrier family 13 member 3 (SLC13A3)

Solute carrier family 13 member 3 (SLC13A3) is a high-affinity, sodium-dependent dicarboxylate cotransporter primarily expressed at the plasma membrane of renal proximal tubule cells, but also found in the brain, liver, placenta, and eye. It mediates the electrogenic uptake of four- to six-carbon dicarboxylates—key intermediates of the Krebs (citric acid) cycle, such as succinate and α-ketoglutarate—as well as glutathione, N-acetyl-L-aspartate, citrate (divalent form), mercaptosuccinate, and itaconate. SLC13A3 functions to maintain cellular nutrition and detoxification, supports energy metabolism by modulating NAD^+/NADH ratios, and plays a critical role in reabsorption of dicarboxylates from glomerular filtrate in the kidney. Pathogenic mutations in the gene cause acute reversible leukoencephalopathy with increased urinary α-ketoglutarate (ARLIAK), and genetic and functional alterations of SLC13A3 have been associated with chronic kidney disease, type 2 diabetes, certain cancers, and neurodevelopmental disorders. No specific therapeutic drugs targeting this transporter are currently approved or widely reported.

Other names

Na+/dicarboxylate cotransporter 3NaDC3NADC3SDCT2NaDC-3hNaDC3NaC3sodium-dependent high-affinity dicarboxylate transporter 2Na(+)-coupled carboxylate transporter 3

Electrogenic sodium-coupled symport of dicarboxylates (transports 3 Na^+ with 1 dicarboxylate into cell), influences intracellular dicarboxylate pool and downstream energy homeostasis