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Comprehensive In Silico Functional Prediction Analysis of CDKL5 by Single Amino Acid Substitution in the Catalytic Domain
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 20; Pages: 12281
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
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. Substitutions predicted as pathogenic were over 88.0% accurate using each of the three tools. The best performance score (accuracy, 97.2%; sensitivity, 100%; specificity, 66.7%; and Matthew’s correlation coefficient (MCC), 0.804) was achieved by combining PolyPhen-2 HumDiv, PolyPhen-2 HumVar, and PROVEAN. This provided comprehensive information that could accurately predict the pathogenicity of the disease, which might be used as an aid for clinical diagnosis.
- Subjects :
- Threonine
Organic Chemistry
Mutation, Missense
General Medicine
Catalysis
Cyclin-Dependent Kinases
Computer Science Applications
Inorganic Chemistry
Amino Acid Substitution
CDKL5
in silico prediction analysis
PolyPhen-2
PROVEAN
SIFT
single amino acid substitutions
Catalytic Domain
Serine
Physical and Theoretical Chemistry
Molecular Biology
Spectroscopy
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 23; Issue 20; Pages: 12281
- Accession number :
- edsair.doi.dedup.....a38e92a61e251c670b7aa2ee54b9696f
- Full Text :
- https://doi.org/10.3390/ijms232012281