Complex interactions between p.His558Arg and linked variants in the sodium voltage-gated channel alpha subunit 5 (NaV1.5)

Figures

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  Figure 1. Schematic representation of the NaV1.5 protein. (A) 2D topology of the protein showing the localization of the p.His558Arg variant in Linker 1 (L1) and the localization of the reported deleterious variants. (B) Schematic representation of the genetic backgrounds in which p.His558Arg was expressed and functionally characterized. (C) Illustration of the membrane composition showing cis and trans allelic backgrounds, where P indicates the presence of the polymorphic p.His558Arg variant and M indicates the presence of a deleterious variant.

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  Figure 2. Haplotypic structure. (A) Haplotypic analysis based on the 1KGP data obtained through combination of variants rs2051211, rs3922844, rs7374004, rs7374540, rs6599222 and rs11710077 found to be in LD with rs1805124. Frequency and count values refer to the sum off all populations; lower case letters correspond to risk alleles; bold haplotypes carry the rs1805124-C allele. Only the top 20 most frequent haplotypes are represented (full list of haplotypes in Table S6). (B) Frequency distribution of each haplotype in all populations analysed. Black arrowheads indicate haplotypes carrying the rs1805124-C allele.

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  Figure 3. Investigation of the rs1805124 allelic status in primates. Primate phylogenetic species tree calculated in www.Timetree.org (Kumar et al., 2017). Values at tree nodes indicate approximate time of lineage divergence. The predicted ancestral state of position 558 is represented by circled H (histidine) or R (arginine). The extant state of position 558 is indicated for each specie analysed. Dots indicate the analysis of several independent individuals of a given species. (A) Detailed view of the Homininae lineage. (B) Full view of the primate species analysed.