Solute carrier family 26 member 3 (SLC26A3) (SLC26A3)

Solute carrier family 26 member 3 (SLC26A3), commonly referred to as Down-Regulated in Adenoma (DRA), is a vital transmembrane transporter located on the apical membrane of intestinal epithelial cells, specifically in the ileum and colon (UniProt P40879). It facilitates the exchange of luminal chloride for intracellular bicarbonate or hydroxide, serving as the primary mechanism for intestinal chloride absorption (PubMed: 28611103). Loss-of-function mutations in SLC26A3 lead to congenital chloride diarrhea (CLD), a condition marked by severe electrolyte loss and dehydration (PubMed: 8944020). In therapeutic development, SLC26A3 is targeted by novel small-molecule inhibitors like DRAinh-A270 to treat chronic constipation by blocking chloride uptake, which increases luminal osmolarity and promotes water retention in the gut (PubMed: 30655315). Additionally, its role in sodium-independent chloride absorption makes it a potential target for managing hypertension and fluid overload (PubMed: 26912540). Reduced expression of SLC26A3 is also a hallmark of inflammatory bowel disease (IBD), where it contributes to the pathogenesis of diarrhea (PubMed: 25113822).

Other names

Down-regulated in adenomaDRAChloride anion exchangerCLDSolute carrier family 26 member 3

Inhibition of the SLC26A3-mediated chloride/bicarbonate exchange to reduce intestinal fluid absorption and increase stool water content.