Three subunits of the amiloride-sensitive Na+ channel, named alpha, beta, and gamma, have previously been cloned in rat colon. The human lung alpha chain (SCNN1A) has also been cloned and its gene localized on chromosome 12p13. We now report the molecular cloning of the human lung beta (SCNN1B) and gamma (SCNN1G) chains. In situ hybridization and pulsed-field electrophoresis experiments demonstrate that both genes are located within a common 400-kb fragment on chromosome 16p12-p13. Screening of the cDNA library reveals two forms of the beta subunit that differ by the presence or absence of a 464-bp fragment in the 3' region. A frameshift in the short form modifies the COOH terminal sequence of the corresponding protein. Since several similar frameshifts mutations have recently been reported in patients affected by a rare form of hypertension, the existence of COOH truncated forms of the beta chain might be of physiological importance.

>sp|P51170|SCAG_HUMAN AMILORIDE-SENSITIVE SODIUM CHANNEL GAMMA-SUBUNIT (EPITHELIAL NA+ CHANNEL GAMMA SUBUNIT) (GAMMA ENAC) (NONVOLTAGE-GATED SODIUM CHANNEL 1 GAMMA SUBUNIT) (SCNEG) (GAMMA NACH) - Homo sapiens (Human).
MAPGEKIKAKIKKNLPVTGPQAPTIKELMRWYCLNTNTHGCRRIVVSRGRLRRLLWIGFTLTAVALILWQCALLVFSFYT
VSVSIKVHFRKLDFPAVTICNINPYKYSTVRHLLADLEQETREALKSLYGFPESRKRREAESWNSVSEGKQPRFSHRIPL
LIFDQDEKGKARDFFTGRKRKVGGSIIHKASNVMHIESKQVVGFQLCSNDTSDCATYTFSSGINAIQEWYKLHYMNIMAQ
VPLEKKINMSYSAEELLVTCFFDGVSCDARNFTLFHHPMHGNCYTFNNRENETILSTSMGGSEYGLQVILYINEEEYNPF
LVSSTGAKVIIHRQDEYPFVEDVGTEIETAMVTSIGMHLTESFKLSEPYSQCTEDGSDVPIRNIYNAAYSLQICLHSCFQ
TKMVEKCGCAQYSQPLPPAANYCNYQQHPNWMYCYYQLHRAFVQEELGCQSVCKEACSFKEWTLTTSLAQWPSVVSEKWL
LPVLTWDQGRQVNKKLNKTDLAKLLIFYKDLNQRSIMESPANSIEMLLSNFGGQLGLWMSCSVVCVIEIIEVFFIDFFSI
IARRQWQKAKEWWAWKQAPPCPEAPRSPQGQDNPALDIDDDLPTFNSALHLPPALGTQVPGTPPPKYNTLRLERAFSNQL
TDTQMLDEL