Molecular pathology and cystogenic propensity of the ADPKD Taiwan founder variant.

ABSTRACT: Renal polycystins (PKD1, PKD2) are ion channel-forming subunits that traffic to principal cell primary cilia. Variants in these proteins cause approximately 95% of autosomal dominant polycystic kidney disease (ADPKD), a common, lethal genetic disorder that lacks effective drug treatments. We assessed the mechanistic impact and pathogenic propensity of 2 disease-associated PKD2 truncating variants, R803X and R654X. Worldwide, hundreds of individuals with ADPKD harbor these germline mutations, including the R803X founder variant first identified within the patient population of Taiwan. Our biochemical, electrophysiological, and super-resolution imaging analyses demonstrated that the pore-truncating R654X variant abolished channel assembly and ciliary trafficking, whereas the R803X variant re

SUBMITTER: Kimura LF 

PROVIDER: S-EPMC12643504 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature