Complementary computational and experimental evaluation of missense variants in the ROMK potassium channel.

ABSTRACT: The renal outer medullary potassium (ROMK) channel is essential for potassium transport in the kidney, and its dysfunction is associated with a salt-wasting disorder known as Bartter syndrome. Despite its physiological significance, we lack a mechanistic understanding of the molecular defects in ROMK underlying most Bartter syndrome-associated mutations. To this end, we employed a ROMK-dependent yeast growth assay and tested single amino acid variants selected by a series of computational tools representative of different approaches to predict each variants' pathogenicity. In one approach, we used in silico saturation mutagenesis, i.e. the scanning of all possible single amino acid substitutions at all sequence positions to estimate their impact on function, and then employed a new machine

SUBMITTER: Ponzoni L 

PROVIDER: S-EPMC7162551 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature