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Analysis of Single-Nucleotide Polymorphisms in Human Voltage-Gated Ion Channels

By Katerina C. Nastou (6532367), Michail A. Batskinis (6532370), Zoi I. Litou (3715846), Stavros J. Hamodrakas (105670) and Vassiliki A. Iconomidou (105667)


Voltage-gated ion channels (VGICs) are one of the largest groups of transmembrane proteins. Due to their major role in the generation and propagation of electrical signals, VGICs are considered important from a medical viewpoint, and their dysfunction is often associated with Channelopathies. We identified disease-associated mutations and polymorphisms in these proteins through mapping missense single-nucleotide polymorphisms from the UniProt and ClinVar databases on their amino acid sequence, considering their special topological and functional characteristics. Statistical analysis revealed that disease-associated SNPs are mostly found in the voltage sensor domain and the pore loop. Both of these regions are extremely important for the activation and ion conductivity of VGICs. Moreover, among the most frequently observed mutations are those of arginine to glutamine, to histidine or to cysteine, which can probably be attributed to the extremely important role of arginine residues in the regulation of membrane potential in these proteins. We suggest that topological information in combination with genetic variation data can contribute toward a better evaluation of the effect of currently unclassified mutations in VGICs. It is hoped that potential associations with certain disease phenotypes will be revealed in the future with the use of similar approaches

Topics: Biophysics, Biochemistry, Medicine, Genetics, Evolutionary Biology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, arginine residues, transmembrane proteins, ion conductivity, Single-Nucleotide Polymorphisms, VGIC, voltage sensor domain, variation data, pore loop, role, acid sequence, mapping missense single-nucleotide polymorphisms, disease phenotypes, topological information, Human Voltage-Gated Ion Channels Voltage-gated ion channels, Statistical analysis, disease-associated SNPs, disease-associated mutations, ClinVar databases
Year: 2019
DOI identifier: 10.1021/acs.jproteome.9b00121.s004
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Provided by: FigShare
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