Seth L Alper, Marina N Chernova, Andrew K Stewart
Among human bicarbonate transporters, two major gene families encode Na-independent Cl- /HCO3 - exchangers: the SLC4 anion exchanger (AE) family , and the SLC26 “sulfate permease” anion transporter family . The SLC4 AE family contains at least three genes, and comprises a subfamily within the larger and phylogenetically more ancient bicarbonate transporter superfamily that includes the Na bicarbonate cotransporters (NBC) and the Na-driven Cl/base exchangers. Mutations in the human AE1 gene cause autosomal dominant spherocytic anemia and distal renal tubular acidosis of both dominant and recessive forms. Anemia is also associated with AE1 mutations in mouse, cow, and zebrafish. Naturally occuring mutations in the human AE2 and AE3 genes have not been detected. The SLC26 family in humans consists of at least 10 members, and includes anion exchangers which exchange chloride for bicarbonate, hydroxyl, sulfate, formate, iodide, and/or oxalate. Mutations in three of these genes cause hereditary disease, including chondrodysplasia (SLC26A2, DTD), diarrhea (A3, down-regulated in adenoma/chloride-losing diarrhea protein: DRA/CLD), and goiter/deafness syndrome (A4, pendrin). Little is known about the acute regulation of these modulators of intracellular and compartmental pH and volume.