Pathogenicity of de novo CACNA1D Ca²⁺ channel variants predicted from sequence co-variation.

ABSTRACT: Voltage-gated L-type Cav1.3 Ca²⁺ channels support numerous physiological functions including neuronal excitability, sinoatrial node pacemaking, hearing, and hormone secretion. De novo missense mutations in the gene of their pore-forming α1-subunit (CACNA1D) induce severe gating defects which lead to autism spectrum disorder and a more severe neurological disorder with and without endocrine symptoms. The number of CACNA1D variants reported is constantly rising, but their pathogenic potential often remains unclear, which complicates clinical decision-making. Since functional tests are time-consuming and not always available, bioinformatic tools further improving pathogenicity potential prediction of novel variants are needed. Here we employed evolutionary analysis considering sequ

SUBMITTER: Tang X 

PROVIDER: S-EPMC11369236 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature