Alternative titles; symbols
HGNC Approved Gene Symbol: SCNN1D
Cytogenetic location: 1p36.33 Genomic coordinates (GRCh38): 1:1,280,436-1,292,025 (from NCBI)
Amiloride-sensitive sodium channels (ASCs) are nonvoltage-gated sodium-permeable ion channels inhibited by the diuretic amiloride. They are well characterized in epithelia where they constitute the rate-limiting step for sodium ion reabsorption. Waldmann et al. (1995) identified a novel homolog of the alpha (600228), beta (600760), and gamma (600761) amiloride-sensitive sodium channels in the EST sequence database and cloned the gene from a human kidney cDNA library. This 3.4-kb cDNA encodes a protein of 638 amino acids. Waldmann et al. (1995) termed this channel the delta isoform and they determined by Northern analysis that it is expressed mainly in ovary, testis, pancreas, and brain. After expression in Xenopus oocytes, the delta isoform induced an amiloride-sensitive sodium current. The current produced by the delta isoform was increased by a factor of 100 after coexpression of the beta subunit and gamma subunit, suggesting to Waldmann et al. (1995) that the delta subunit is part of a novel heteromultimeric channel formed of 3 subunits with the same overall structure but no more than 27-29% sequence identity among them. The pharmacology, sensitivity to amiloride, conductance, and ionic selectivity of the delta/beta-gamma channel were different from those of the alpha/beta-gamma channel.
Molecular cloning of the epithelial amiloride-sensitive sodium channel demonstrated that it is made up of at least 3 homologous subunits, termed alpha, beta, and gamma, which are also homologs of the degenerins of C. elegans, proteins considered to be probable neuronal ion channels (Waldmann et al., 1996). Gain-of-function mutations of members of this group of ion channels are involved in hereditary diseases. Mutations of the C. elegans degenerins are the major known cause of neurodegeneration in the nematode, and gain of function of the amiloride-sensitive sodium channel beta-subunit or gamma-subunit is the cause of Liddle syndrome (177200), a form of hereditary hypertension. The gene encoding the alpha subunit (SCNN1A) maps to 12p13; the genes encoding the beta subunit (SCNN1B) and gamma subunit (SCNN1G) map within a 400-kb fragment on 16p12.
By isotopic in situ hybridization, Waldmann et al. (1996) mapped the gene encoding delta (SCNN1D) to 1p36.3-p36.2.
Waldmann, R., Bassilana, F., Voilley, N., Lazdunski, M., Mattei, M.-G. Assignment of the human amiloride-sensitive Na(+) channel delta isoform to chromosome 1p36.3-p36.2. Genomics 34: 262-263, 1996. [PubMed: 8661065] [Full Text: https://doi.org/10.1006/geno.1996.0282]
Waldmann, R., Champigny, G., Bassilana, F., Voilley, N., Lazdunski, M. Molecular cloning and functional expression of a novel amiloride-sensitive Na(+) channel. J. Biol. Chem. 270: 27411-27414, 1995. [PubMed: 7499195] [Full Text: https://doi.org/10.1074/jbc.270.46.27411]