STRUCTURAL ORGANIZATION OF THE GENE ENCODING THE ALPHA-SUBUNIT OF THEHUMAN AMILORIDE-SENSITIVE EPITHELIAL SODIUM-CHANNEL

The human amiloride-sensitive epithelial sodium channel (ENaC) is a me mber of the degenerin/ENaC family of ion channels and regulates fluid and electrolyte absorption across a number of epithelia, including kid ney, colon and lune. Native ENaC has been shown to be a multimer made up of at least three homologous subunits (alpha, beta, gamma) and muta tions affecting the channel complex have been identified in various hu man diseases. ''Gain of function'' mutations in one of the three ENaC subunits have been found to cause pseudoaldosteronism (Liddle's syndro me) and ENaC ''reduction of function'' mutations are found in patients affected with the recessive form of pseudohypoaldosteronism (PHA) typ e 1. In this report, we describe the genomic organisation of the human alpha ENaC gene. Human alpha ENaC consists of 13 exons spanning 17 kb on chromosome 12p13 and contains at least eight Alu sequences. In add ition to the intron/exon boundaries, we have deciphered almost all the intron sequences and 475 bp of the CCAAT-less and TATA-less 5' flanki ng region.