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Bioinformatics analysis of non-synonymous variants in the KLF genes related to cardiac diseases.
- Source :
-
Gene [Gene] 2018 Apr 15; Vol. 650, pp. 68-76. Date of Electronic Publication: 2018 Feb 02. - Publication Year :
- 2018
-
Abstract
- Kruppel-like Factors (KLF) are responsible for regulating many genes involved in physiological and pathological processes. They are characterized by three conserved zinc-fingers in the DNA-binding domain, wherein mutations could affect the binding efficiency and transcription regulation. This study aimed to perform bioinformatics analysis to determine the most deleterious non-synonymous variants in KLFs involved in cardiac development and diseases, and their effects over the protein structure and stability. Eight hundred and fifty non-synonymous variants were found in seven KLFs related to cardiac diseases. Seventeen algorithms were used to predict the effect of selected variants over the structure and function of seven KLFs. The Top3 variants were selected in each category of conserved and non-conserved residues in the zinc-finger (ZF) domain. KLF5 p.Cys410Phe was the only variant predicted as deleterious in all algorithms, occurring in a conserved residue of zinc ion interaction. KLF15 p.Arg364Pro was the only variant predicted to affect the DNA-binding, and also occurs in a conserved ZF-domain. Our bioinformatics analysis determined potential variants that may lead to development of cardiac diseases, as well as reinforced the importance of KLF analysis in vitro and in vivo.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Amino Acid Substitution
Binding Sites genetics
Computational Biology
Conserved Sequence
Humans
Kruppel-Like Transcription Factors chemistry
Kruppel-Like Transcription Factors metabolism
Models, Molecular
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
Zinc Fingers genetics
Heart Diseases genetics
Kruppel-Like Transcription Factors genetics
Mutation, Missense
Sequence Homology, Amino Acid
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0038
- Volume :
- 650
- Database :
- MEDLINE
- Journal :
- Gene
- Publication Type :
- Academic Journal
- Accession number :
- 29408733
- Full Text :
- https://doi.org/10.1016/j.gene.2018.01.085