Members of the SLC4A family couple the transport of bicarbonate (HCO3-) with sodium ions (Na+); they being members 4, 5, 7 and 9. SLC4A4 (aka NBCe1) is an electrogenic sodium/bicarbonate cotransporter with a Na+:HCO3- stoichiometry of 1:3, although it can also be 1:2 (Burnham et al. 1997). SLC4A4 encodes a protein which is expressed in the kidney and pancreas, with lesser expression in many other tissues (Abuladze et al. 1998). Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis (pRTA) (results in accumulation of acid in the body due to a failure of the kidneys to effectively acidify urine) with ocular abnormalities (Igarashi et al. 1999).
SLC4A5 encodes a protein which is expressed in liver, spleen and testes, with lower levels expressed in parts of the brain and kidney (Sassani et al. 2002). It may have a housekeeping function in regulating the pH of these tissues (Pushkin et al. 2000). SLC4A7 (aka NBC3, NBCn1) encodes a protein which performs electroneutral cotransport of Na+ and HCO3- with a 1:1 stoichiometry. It is highly expressed in testes and spleen and, to a lesser extent, in many other tissues including heart, muscle, kidney and GI tract (Pushkin et al. 1999).
SLC4A9 (aka AE4) was originally thought to exchange Cl- with HCO3- (hence the name AE4) but this has not been reported. Consensus has emerged that it is indeed a Na+/HCO3- co-transporter (Lipovich et al. 2001). It is predominantly expressed in the kidney, salivary glands, testes, thyroid glands and trachea (Parker et al. 2001).