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Gene Review

SLC9A4  -  solute carrier family 9, subfamily A (NHE4...

Homo sapiens

Synonyms: NHE-4, NHE4, Na(+)/H(+) exchanger 4, Sodium/hydrogen exchanger 4, Solute carrier family 9 member 4
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Disease relevance of SLC9A4

  • Acute acidosis and alkalosis and chronic acidosis had no effect on NHE3 and NHE4 expression and localization [1].
  • We hypothesized that acid/base disturbances might affect the expression of Na(+)/H(+) exchanger (NHE) isoforms in salivary glands and determined the expression and cellular distribution of NHE3 and NHE4 in rat submandibular glands of controls and after imposed acute or chronic metabolic acidosis or alkalosis in vivo [1].

High impact information on SLC9A4

  • Unlike other Na-H exchanger isoforms, NHE-4 transfected into NHE-deficient mutant fibroblasts demonstrated no amiloride-inhibitable sodium uptake, under basal or acid-loaded isoosmotic conditions [2].
  • We conclude that NHE-4 is an unusual isoform of sodium-hydrogen exchangers that may play a specialized supplementary role in cell volume regulation [2].
  • The results demonstrate, for the first time, the presence of NHE4 protein in salivary glands [1].
  • In addition, we identified a histamine- and pH(i)-sensitive Na+/H+ exchanger in HGT-1 cells, which might correspond to the functional expression of the NHE4 isoform that has been detected in gastric epithelial cells as well as in primary cultured parietal cells [3].
  • However, there is no evidence that there is expression of NHE-3 or NHE-4 in peripheral blood cells [4].

Biological context of SLC9A4

  • NHE2, NHE3, and NHE4 are, however, restricted in their tissue distribution, suggesting roles in specialized functions of these epithelial tissues [5].

Anatomical context of SLC9A4

  • The results showed NHE3 and NHE4 transcript expression and protein abundance in rat submandibular gland [1].
  • Similarly there was no evidence of expression of NHE-4 in the peripheral blood cell preparations [4].

Analytical, diagnostic and therapeutic context of SLC9A4

  • By in situ hybridization, NHE-4 expression in the rat kidney was found to be limited to the inner renal medullary collecting tubules, the region of highest tissue osmolarity fluctuations in the body [2].
  • The molecular identity of the AE and NHE isoforms was investigated by RT-PCR that confirmed the presence of NHE1 and NHE3 transcripts in addition to NHE4 [6].


  1. Na(+)/H(+) exchanger isoforms are differentially regulated in rat submandibular gland during acid/base disturbances in vivo. Oehlke, O., Sprysch, P., Rickmann, M., Roussa, E. Cell Tissue Res. (2006) [Pubmed]
  2. A unique sodium-hydrogen exchange isoform (NHE-4) of the inner medulla of the rat kidney is induced by hyperosmolarity. Bookstein, C., Musch, M.W., DePaoli, A., Xie, Y., Villereal, M., Rao, M.C., Chang, E.B. J. Biol. Chem. (1994) [Pubmed]
  3. The cultured human gastric cells HGT-1 express the principal transporters involved in acid secretion. Carmosino, M., Procino, G., Casavola, V., Svelto, M., Valenti, G. Pflugers Arch. (2000) [Pubmed]
  4. Sodium-hydrogen exchange isoform expression in blood cells: implications for studies in diabetes mellitus. Rutherford, P., Pizzonia, J., Abu-Alfa, A., Biemesderfer, D., Reilly, R., Aronson, P. Exp. Clin. Endocrinol. Diabetes (1997) [Pubmed]
  5. Hormonal regulation, pharmacology, and membrane sorting of vertebrate Na+/H+ exchanger isoforms. Noël, J., Pouysségur, J. Am. J. Physiol. (1995) [Pubmed]
  6. Expression of cation exchanger NHE and anion exchanger AE isoforms in primary human bone-derived osteoblasts. Mobasheri, A., Golding, S., Pagakis, S.N., Corkey, K., Pocock, A.E., Fermor, B., O'BRIEN, M.J., Wilkins, R.J., Ellory, J.C., Francis, M.J. Cell Biol. Int. (1998) [Pubmed]
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