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Gene Review

SLC9A5  -  solute carrier family 9, subfamily A (NHE5...

Homo sapiens

Synonyms: NHE-5, NHE5, Na(+)/H(+) exchanger 5, Sodium/hydrogen exchanger 5, Solute carrier family 9 member 5
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Disease relevance of SLC9A5

  • Given the allelic association, further evaluation of the role of NHE5 in ESRD susceptibility appears warranted [1].
  • Mutation analysis of the sodium/hydrogen exchanger gene (NHE5) in familial paroxysmal kinesigenic dyskinesia [2].

High impact information on SLC9A5

  • The neuronal Na(+)/H(+) exchanger NHE5 isoform not only resides in the plasma membrane but also accumulates in recycling vesicles by means of clathrin-mediated endocytosis [3].
  • To further investigate the underlying molecular mechanisms, a human brain cDNA library was screened for proteins that interact with the cytoplasmic C-terminal region of NHE5 by using yeast two-hybrid methodology [3].
  • Full-length NHE5 and beta-arrestin2 also associated in intact cells, as revealed by their coimmunoprecipitation from extracts of transfected CHO cells [3].
  • By contrast, disruption of the F-actin cytoskeleton with cytochalasin D increased cell surface NHE5 activity and abundance [4].
  • Similarly, in nerve growth factor-differentiated neuroendocrine PC12 cells and primary hippocampal neurons, immunolabeling of NHE5 was detected in endomembrane vesicles in the perinuclear region of the cell body but also along the processes [4].

Biological context of SLC9A5


Anatomical context of SLC9A5


Associations of SLC9A5 with chemical compounds

  • We propose that RACK1 activates NHE5 both by integrin-dependent and independent pathways, which may coordinate cellular ion homeostasis during cell-matrix adhesion [8].

Regulatory relationships of SLC9A5

  • Together, these results suggest that SCAMP2 regulates NHE5 transit through recycling endosomes and promotes its surface targeting in an Arf6-dependent manner [9].

Other interactions of SLC9A5

  • The intron/exon organization of the NHE5 gene was analyzed and found to be very similar to that of the NHE3 gene [6].
  • To date, 5 isoforms of NHE have been cloned in mammals (NHE1 to NHE5) [1].
  • The expression of the isoforms NHE2 to NHE5 is restricted to specific tissues and the pattern of their expression, as well as their subcellular localization indicate that they fulfill specialized functions [10].
  • The segmental location and function of NHE-5 and NHE-6 in the kidney are unknown at present [11].

Analytical, diagnostic and therapeutic context of SLC9A5

  • RT-PCR analysis of rat kidney RNA using primers specific for NHE isoforms -2, -3, -4 and rat brain RNA using primer specific for NHE-5 isoform yielded products of expected size, whereas WBC depleted RNA under identical conditions yielded no products [12].


  1. Human Na+/H+ exchanger genes : identification of polymorphisms by radiation hybrid mapping and analysis of linkage in end-stage renal disease. Yu, H., Freedman, B.I., Rich, S.S., Bowden, D.W. Hypertension (2000) [Pubmed]
  2. Mutation analysis of the sodium/hydrogen exchanger gene (NHE5) in familial paroxysmal kinesigenic dyskinesia. Spacey, S.D., Szczygielski, B.I., McRory, J.E., Wali, G.M., Wood, N.W., Snutch, T.P. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  3. beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform. Szabó, E.Z., Numata, M., Lukashova, V., Iannuzzi, P., Orlowski, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Clathrin-mediated endocytosis and recycling of the neuron-specific Na+/H+ exchanger NHE5 isoform. Regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton. Szaszi, K., Paulsen, A., Szabo, E.Z., Numata, M., Grinstein, S., Orlowski, J. J. Biol. Chem. (2002) [Pubmed]
  5. Molecular cloning and physical and genetic mapping of a novel human Na+/H+ exchanger (NHE5/SLC9A5) to chromosome 16q22.1. Klanke, C.A., Su, Y.R., Callen, D.F., Wang, Z., Meneton, P., Baird, N., Kandasamy, R.A., Orlowski, J., Otterud, B.E., Leppert, M. Genomics (1995) [Pubmed]
  6. Molecular cloning, genomic organization, and functional expression of Na+/H+ exchanger isoform 5 (NHE5) from human brain. Baird, N.R., Orlowski, J., Szabó, E.Z., Zaun, H.C., Schultheis, P.J., Menon, A.G., Shull, G.E. J. Biol. Chem. (1999) [Pubmed]
  7. Molecular cloning and functional expression of a rat Na+/H+ exchanger (NHE5) highly expressed in brain. Attaphitaya, S., Park, K., Melvin, J.E. J. Biol. Chem. (1999) [Pubmed]
  8. RACK1 associates with NHE5 in focal adhesions and positively regulates the transporter activity. Onishi, I., Lin, P.J., Diering, G.H., Williams, W.P., Numata, M. Cell. Signal. (2007) [Pubmed]
  9. Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5. Diering, G.H., Church, J., Numata, M. J. Biol. Chem. (2009) [Pubmed]
  10. Na(+)/H(+)exchangers: linking osmotic dysequilibrium to modified cell function. Ritter, M., Fuerst, J., Wöll, E., Chwatal, S., Gschwentner, M., Lang, F., Deetjen, P., Paulmichl, M. Cell. Physiol. Biochem. (2001) [Pubmed]
  11. The Na+/H+ exchanger gene family. Burckhardt, G., Di Sole, F., Helmle-Kolb, C. J. Nephrol. (2002) [Pubmed]
  12. NHE-1 is the sodium-hydrogen exchanger isoform present in erythroid cells. Sarangarajan, R., Dhabia, N., Soleimani, M., Soliemani, M., Baird, N., Joiner, C. Biochim. Biophys. Acta (1998) [Pubmed]
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