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Gene Review

Slc26a6  -  solute carrier family 26, member 6

Mus musculus

Synonyms: Anion exchange transporter, B930010B04Rik, CFEX, Cfex, Chloride-formate exchanger, ...
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Disease relevance of Slc26a6


High impact information on Slc26a6

  • These findings point to a critical role for Slc26a6 in gastrointestinal oxalate secretion and suggest a genetic explanation for a common form of renal stone disease in humans [2].
  • To investigate the possible interaction of NHE3 and CFEX with the PDZ-domain-containing scaffolding protein PDZK1, we performed a series of in vitro interaction assays with GST-fusion proteins and native brush border membrane proteins [5].
  • To determine whether PDZK1 interaction is essential for brush border localization of NHE3 and CFEX in vivo, we examined the expression of NHE3 and CFEX in kidneys of wild-type and PDZK1-null mutant mice by both Western analysis and immunocytochemistry [5].
  • Functional expression studies in Xenopus oocytes demonstrated that CFEX mediates Cl(-)-formate exchange [6].
  • Given its wide tissue distribution, CFEX also may contribute to transcellular Cl(-) transport in additional epithelia such as the pancreas and contribute to transmembrane Cl(-) transport in nonepithelial tissues such as the heart [6].

Chemical compound and disease context of Slc26a6


Biological context of Slc26a6


Anatomical context of Slc26a6

  • Whereas Slc26a6 is capable of Cl(-), SO, formate, and oxalate uptake when expressed in Xenopus laevis oocytes, Slc26a1 transports only SO and oxalate [10].
  • To assess the contribution of the putative anion transporter (PAT)1 (Slc26a6) to transepithelial oxalate transport, we compared the unidirectional and net fluxes of oxalate across isolated, short-circuited segments of the distal ileum of wild-type (WT) mice and Slc26a6 null mice [knockout (KO)] [11].
  • We conclude that Slc26a6 is the predominant Cl(-)-HCO(3)(-) and Cl(-)-OH(-) exchanger of the myocardium and that Slc26a6 is negatively regulated upon alpha-adrenergic stimulation [12].
  • We conclude that Slc26a6 mediates oxalate-stimulated NaCl absorption, contributes to apical membrane Cl-/base exchange in the kidney proximal tubule, and also plays an important role in HCO3- secretion in the duodenum [8].
  • In the duodenum, the baseline rate of HCO3- secretion measured in mucosal tissue mounted in Ussing chambers was decreased by approximately 30% (P<0.03), whereas the forskolin-stimulated component of HCO3- secretion was the same in wild-type and Slc26a6-/- mice [8].

Associations of Slc26a6 with chemical compounds

  • The data indicate that Slc26a6 encodes an apical Cl(-)/formate/oxalate and Cl(-)/base exchanger and reveal significant mechanistic differences between apical and basolateral oxalate exchangers of the proximal tubule [10].
  • Measurement of intracellular pH during the removal of extracellular Cl(-) in the presence and absence of HCO indicates that Slc26a6 functions as both a Cl(-)/HCO and a Cl(-)/OH(-) exchanger; simultaneous membrane hyperpolarization during these experimental maneuvers reveals that HCO and OH(-) transport mediated by Slc26a6 is electrogenic [10].
  • We conclude that mouse Slc26a6 has affinity for oxalate, sulfate, and HCO(3)(-) in addition to Cl(-) and formate and can function in multiple exchange modes involving pairs of these anions [13].
  • Measurements of uptake of [(14)C]oxalate, [(14)C]PAH, and [(35)S]sulfate indicated that Slc26a6 can mediate transport of oxalate and sulfate but not PAH [13].
  • Slc26a6: a cardiac chloride-hydroxyl exchanger and predominant chloride-bicarbonate exchanger of the mouse heart [12].

Other interactions of Slc26a6

  • Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1 [10].
  • Adult hearts expressed Slc26a3 and Slc4a1-3 mRNAs at similar levels, while Slc26a6 mRNA was about seven-fold higher than AE3, which was more abundant than any other [12].
  • We now report the cDNA cloning of CFEX, a mouse pendrin homolog with expression in the kidney by Northern analysis [6].

Analytical, diagnostic and therapeutic context of Slc26a6


  1. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Jiang, Z., Asplin, J.R., Evan, A.P., Rajendran, V.M., Velazquez, H., Nottoli, T.P., Binder, H.J., Aronson, P.S. Nat. Genet. (2006) [Pubmed]
  2. A key stone cop regulates oxalate homeostasis. Kleta, R. Nat. Genet. (2006) [Pubmed]
  3. Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO(3)(-) secretion: relevance to cystic fibrosis. Wang, Y., Soyombo, A.A., Shcheynikov, N., Zeng, W., Dorwart, M., Marino, C.R., Thomas, P.J., Muallem, S. EMBO J. (2006) [Pubmed]
  4. Chloride conductance of CFTR facilitates basal Cl-/HCO3- exchange in the villous epithelium of intact murine duodenum. Simpson, J.E., Gawenis, L.R., Walker, N.M., Boyle, K.T., Clarke, L.L. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  5. Role of PDZK1 in membrane expression of renal brush border ion exchangers. Thomson, R.B., Wang, T., Thomson, B.R., Tarrats, L., Girardi, A., Mentone, S., Soleimani, M., Kocher, O., Aronson, P.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Identification of a chloride-formate exchanger expressed on the brush border membrane of renal proximal tubule cells. Knauf, F., Yang, C.L., Thomson, R.B., Mentone, S.A., Giebisch, G., Aronson, P.S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  7. Anion exchangers in flux: functional differences between human and mouse SLC26A6 polypeptides. Alper, S.L., Stewart, A.K., Chernova, M.N., Zolotarev, A.S., Clark, J.S., Vandorpe, D.H. Novartis Found. Symp. (2006) [Pubmed]
  8. Renal and intestinal transport defects in Slc26a6-null mice. Wang, Z., Wang, T., Petrovic, S., Tuo, B., Riederer, B., Barone, S., Lorenz, J.N., Seidler, U., Aronson, P.S., Soleimani, M. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  9. Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct. Ishiguro, H., Namkung, W., Yamamoto, A., Wang, Z., Worrell, R.T., Xu, J., Lee, M.G., Soleimani, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2007) [Pubmed]
  10. Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1. Xie, Q., Welch, R., Mercado, A., Romero, M.F., Mount, D.B. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  11. Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice. Freel, R.W., Hatch, M., Green, M., Soleimani, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  12. Slc26a6: a cardiac chloride-hydroxyl exchanger and predominant chloride-bicarbonate exchanger of the mouse heart. Alvarez, B.V., Kieller, D.M., Quon, A.L., Markovich, D., Casey, J.R. J. Physiol. (Lond.) (2004) [Pubmed]
  13. Specificity of anion exchange mediated by mouse Slc26a6. Jiang, Z., Grichtchenko, I.I., Boron, W.F., Aronson, P.S. J. Biol. Chem. (2002) [Pubmed]
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