Heterogeneity in Lowe Syndrome: Mutations Affecting the Phosphatase Domain of OCRL1 Differ in Impact on Enzymatic Activity and Severity of Cellular Phenotypes.

ABSTRACT: Lowe Syndrome (LS) is a condition due to mutations in the OCRL1 gene, characterized by congenital cataracts, intellectual disability, and kidney malfunction. Unfortunately, patients succumb to renal failure after adolescence. This study is centered in investigating the biochemical and phenotypic impact of patient's OCRL1 variants (OCRL1^VAR). Specifically, we tested the hypothesis that some OCRL1^VAR are stabilized in a non-functional conformation by focusing on missense mutations affecting the phosphatase domain, but not changing residues involved in binding/catalysis. The pathogenic and conformational characteristics of the selected variants were evaluated in silico and our results revealed some OCRL1^VAR to be benign, while others are pathogenic. The

SUBMITTER: Lee JJ 

PROVIDER: S-EPMC10135975 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature