Simple method for assessment of pathogenicity of cyclin-dependent kinase-like 5 mutations using Phos-tag SDS-PAGE

Abstract

Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase, and mutations in the CDKL5 gene lead to a neurodevelopmental disorder known as CDKL5 deficiency disorder (CDD). As many missense mutations were observed within the CDKL5 gene encoding the catalytic domain, the phosphorylation activity of CDKL5 was considered to be closely associated to CDD. However, CDKL5 mutation activity has rarely been analyzed. Therefore, we developed an efficient method for detecting CDKL5 activity, using Phos-tag SDS-PAGE. In this review, I introduce an outline of the method and an assessment for pathogenicity of CDKL5 mutations, including an identified mutation, Y177C.