Disease relevance of SCNN1B

• Liddle's syndrome of hypertension and pseudoaldosteronism has been shown to arise from mutations in SCNN1B and SCNN1G [1].
• Two of the six hypertensive patients with missense mutation in the SCNN1B gene showed atypical renin and aldosterone levels, though one of them was diagnosed with renovascular hypertension [2].

High impact information on SCNN1B

• RESULTS: In controls, aldosterone stimulated J(Na) and induced ENaC beta- and gamma-subunit expression, whereas this response was virtually abolished in UC [3].
• Gain-of-function mutations in ENaC beta and gamma subunits cause pseudoaldosteronism (Liddle's syndrome), a severe form of salt-sensitive hypertension [4].
• A missense mutation (G37S) of the human ENaC beta subunit that causes loss of ENaC function and PHA-1 replaces a glycine that is conserved in the N-terminus of all members of the ENaC gene family [5].
• Expression of the amiloride-sensitive sodium channel beta subunit gene in human B lymphocytes [6].
• This study demonstrates that the ENaC beta subunit gene is expressed in human B cell lines, peripheral blood lymphocytes, and lymph node at the mRNA level [6].

Biological context of SCNN1B

• In the SCNN1B gene, we identified three missense mutations, P592S (n=3), T594M (n=2), and E632K (n=1) in a heterozygous state in addition to four synonymous ones, Ile515 (n=1), Ser520 (n=19), Ser533 (n=1), and Thr594 (n=11) [2].
• Genetic analysis of ENaC in a Chinese family with Liddle's syndrome revealed P616H of SCNN1B coaggregated with the phenotype, while this variant was not detected in 100 unrelated subjects [7].
• An AvaII PCR/RFLP in an exon of the canine gene for the beta subunit of the amiloride-sensitive sodium channel (SCNN1B) [8].

Anatomical context of SCNN1B

• In conclusion, the IL-2(-/-) mucosa exhibits impaired electroneutral Na(+)-Cl(-) absorption and electrogenic Na(+) transport due to reduced mRNA and protein expression of NHE3 and ENaC beta- and gamma-subunit mRNA [9].
• The results showed that T lymphocytes express the ENaC gamma subunit mRNA, and B lymphocytes the ENaC beta subunit mRNA [10].
• Functional expression of these splice variants with hENaC beta and gamma subunits produced loss-of-channel activity in the Xenopus oocyte expression system [11].

Other interactions of SCNN1B

• 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 [12].
• Taken together, these results show that UC results mainly in decreased expression of the apical ENaC beta- and gamma-subunits, as well as the basolateral Na+, K+-ATPase alpha1- and beta1-isoforms [12].
• ENaC with Liddle's syndrome mutation is also inhibited during activation of CFTR, suggesting that the C-terminus of the ENaC beta-subunit is not important for this functional interrelation [13].

References