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Gene Review

SCNN1A  -  sodium channel, non voltage gated 1 alpha...

Homo sapiens

Synonyms: Alpha-ENaC, Alpha-NaCH, Amiloride-sensitive sodium channel subunit alpha, BESC2, ENaCA, ...
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Disease relevance of SCNN1A


High impact information on SCNN1A


Biological context of SCNN1A


Anatomical context of SCNN1A


Associations of SCNN1A with chemical compounds

  • These results confirm that alpha ENaC is an aldosterone-induced transcript in the collecting duct and delineates the molecular mechanism for this effect [10].
  • Assays of transcriptional activity showed that dexamethasone caused concentration-dependent activation of the human alpha-ENaC promoter (EC50 approximately 5 nM) but, despite its clear effect on GNa, T2 had no effect upon the transcriptional response to dexamethasone [16].
  • Thyroid hormone potentiates glucocorticoid-evoked airway Na+ transport without affecting alpha-ENaC transcription [16].
  • Although hENaCdelta homomer was also significantly activated by capsazepine, unexpectedly, capsazepine had no effect on hENaCalpha and caused a slight decrease on the hENaCalphabetagamma current [17].
  • Aldosterone did not, however, affect alpha-ENaC expression in the cortical collecting duct (CCD), which showed weak and dispersed labeling similar to that in rats treated with lithium alone [18].

Other interactions of SCNN1A

  • PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells [19].
  • We have identified the wild-type and three splice variants of the human alpha ENaC (h alpha ENaC) from the human lung cell line H441, using RT-PCR [20].
  • A prostasin-preferred poly-basic cleavage site was found in the extracellular domains of the ENaC alpha- and beta-subunits, and may present a mechanism for prostasin activation [21].
  • UC was associated with substantial decreases in the expression of the ENaC beta- and gamma-subunit proteins and mRNAs, whereas the decrease in ENaC alpha-subunit protein detected by immunolocalization was less marked [22].
  • The NPPA T2238C and SCNN1A A663T were associated with decreased fasting insulin levels after adjusting for body mass index (P=0.015 and 0.028) [23].

Analytical, diagnostic and therapeutic context of SCNN1A


  1. Association of a sodium channel alpha subunit promoter variant with blood pressure. Iwai, N., Baba, S., Mannami, T., Ogihara, T., Ogata, J. J. Am. Soc. Nephrol. (2002) [Pubmed]
  2. Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome. Sheridan, M.B., Fong, P., Groman, J.D., Conrad, C., Flume, P., Diaz, R., Harris, C., Knowles, M., Cutting, G.R. Hum. Mol. Genet. (2005) [Pubmed]
  3. Binding of the proline-rich region of the epithelial Na+ channel to SH3 domains and its association with specific cellular proteins. McDonald, F.J., Welsh, M.J. Biochem. J. (1995) [Pubmed]
  4. Delayed clearance of fetal lung liquid and sodium transport--genetic predisposition not evident yet. Hallman, M. Acta Paediatr. (2005) [Pubmed]
  5. A novel splice-site mutation in the gamma subunit of the epithelial sodium channel gene in three pseudohypoaldosteronism type 1 families. Strautnieks, S.S., Thompson, R.J., Gardiner, R.M., Chung, E. Nat. Genet. (1996) [Pubmed]
  6. Cytokine-dependent transcriptional down-regulation of epithelial sodium channel in ulcerative colitis. Amasheh, S., Barmeyer, C., Koch, C.S., Tavalali, S., Mankertz, J., Epple, H.J., Gehring, M.M., Florian, P., Kroesen, A.J., Zeitz, M., Fromm, M., Schulzke, J.D. Gastroenterology (2004) [Pubmed]
  7. The carboxyl terminus of the alpha-subunit of the amiloride-sensitive epithelial sodium channel binds to F-actin. Mazzochi, C., Bubien, J.K., Smith, P.R., Benos, D.J. J. Biol. Chem. (2006) [Pubmed]
  8. Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel. Voilley, N., Bassilana, F., Mignon, C., Merscher, S., Mattéi, M.G., Carle, G.F., Lazdunski, M., Barbry, P. Genomics (1995) [Pubmed]
  9. The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis. Stanke, F., Becker, T., Cuppens, H., Kumar, V., Cassiman, J.J., Jansen, S., Radojkovic, D., Siebert, B., Yarden, J., Ussery, D.W., Wienker, T.F., Tümmler, B. Hum. Genet. (2006) [Pubmed]
  10. The alpha-subunit of the epithelial sodium channel is an aldosterone-induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5'-flanking region of the gene. Mick, V.E., Itani, O.A., Loftus, R.W., Husted, R.F., Schmidt, T.J., Thomas, C.P. Mol. Endocrinol. (2001) [Pubmed]
  11. An Alu cassette in the human epithelial sodium channel. Oh, Y.S., Lee, S., Won, C., Warnock, D.G. Biochim. Biophys. Acta (2001) [Pubmed]
  12. Steroids and exogenous gamma-ENaC subunit modulate cation channels formed by alpha-ENaC in human B lymphocytes. Ma, H.P., Al-Khalili, O., Ramosevac, S., Saxena, S., Liang, Y.Y., Warnock, D.G., Eaton, D.C. J. Biol. Chem. (2004) [Pubmed]
  13. Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate alpha-ENaC and sgk1 expression in renal collecting duct epithelia. Thomas, C.P., Liu, K.Z., Vats, H.S. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  14. N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells. Rochat, T., Lacroix, J.S., Jornot, L. J. Cell. Physiol. (2004) [Pubmed]
  15. Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis. Ishibashi, K., Marumo, F. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  16. Thyroid hormone potentiates glucocorticoid-evoked airway Na+ transport without affecting alpha-ENaC transcription. Richard, K., Ramminger, S.J., Forsyth, L., Burchell, A., Wilson, S.M. FEBS Lett. (2004) [Pubmed]
  17. Capsazepine is a novel activator of the delta subunit of the human epithelial Na+ channel. Yamamura, H., Ugawa, S., Ueda, T., Nagao, M., Shimada, S. J. Biol. Chem. (2004) [Pubmed]
  18. Lithium-induced NDI in rats is associated with loss of alpha-ENaC regulation by aldosterone in CCD. Nielsen, J., Kwon, T.H., Frøkiaer, J., Knepper, M.A., Nielsen, S. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  19. PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells. Hong, G., Lockhart, A., Davis, B., Rahmoune, H., Baker, S., Ye, L., Thompson, P., Shou, Y., O'Shaughnessy, K., Ronco, P., Brown, J. FASEB J. (2003) [Pubmed]
  20. Cloning and functional studies of splice variants of the alpha-subunit of the amiloride-sensitive Na+ channel. Tucker, J.K., Tamba, K., Lee, Y.J., Shen, L.L., Warnock, D.G., Oh, Y. Am. J. Physiol. (1998) [Pubmed]
  21. Biochemical characterization of prostasin, a channel activating protease. Shipway, A., Danahay, H., Williams, J.A., Tully, D.C., Backes, B.J., Harris, J.L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  22. Decreased expression of apical Na+ channels and basolateral Na+, K+-ATPase in ulcerative colitis. Greig, E.R., Boot-Handford, R.P., Mani, V., Sandle, G.I. J. Pathol. (2004) [Pubmed]
  23. Hypertension genes are genetic markers for insulin sensitivity and resistance. Guo, X., Cheng, S., Taylor, K.D., Cui, J., Hughes, R., Quiñones, M.J., Bulnes-Enriquez, I., De la Rosa, R., Aurea, G., Yang, H., Hsueh, W., Rotter, J.I. Hypertension (2005) [Pubmed]
  24. Expression of epithelial sodium channel alpha-subunit mRNAs with alternative 5'-untranslated regions in the developing human lung. Banasikowska, K., Post, M., Cutz, E., O'Brodovich, H., Otulakowski, G. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  25. Oxidative stress disrupts glucocorticoid hormone-dependent transcription of the amiloride-sensitive epithelial sodium channel alpha-subunit in lung epithelial cells through ERK-dependent and thioredoxin-sensitive pathways. Wang, H.C., Zentner, M.D., Deng, H.T., Kim, K.J., Wu, R., Yang, P.C., Ann, D.K. J. Biol. Chem. (2000) [Pubmed]
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