Comprehensive In Silico Functional Prediction Analysis of CDKL5 by Single Amino Acid Substitution in the Catalytic Domain.

ABSTRACT: Cyclin-dependent kinase-like 5 (CDKL5) is a serine/threonine protein kinase whose pathological mutations cause CDKL5 deficiency disorder. Most missense mutations are concentrated in the catalytic domain. Therefore, anticipating whether mutations in this region affect CDKL5 function is informative for clinical diagnosis. This study comprehensively predicted the pathogenicity of all 5700 missense substitutions in the catalytic domain of CDKL5 using in silico analysis and evaluating their accuracy. Each missense substitution was evaluated as "pathogenic" or "benign". In silico tools PolyPhen-2 HumDiv mode/HumVar mode, PROVEAN, and SIFT were selected individually or in combination with one another to determine their performance using 36 previously reported mutations as a reference. Substitutio

SUBMITTER: Yoshimura Y 

PROVIDER: S-EPMC9603577 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature