Voltage-Gated Sodium Channel NaV1.2: Structural Perspective of the Genetic Variability

Figures

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  Fig. 1. Methodology used in this work

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  Fig. 2. Schematic representation of the distribution of inter-species differences. Blue boxes represent the four domains of the Nav1.2 protein and numbers indicate a variable position between species

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  Fig. 3. Conservation profile of the Nav1.2 protein. a Distribution of the conservation scores extracted from the ConSurf server. Black circles represent the residues that differ between species, while grey circles represent the conserved residues between humans and other mammalian species. b Mann-Whitney test of conservation scores of Nav1.2. Data are represented as mean ± SD, **** p<0.0001

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  Fig. 4. Partial alignment of human variants annotated at gnomAD and observed in the sequence of non-human mammals

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  Fig. 5. Structure of the Nav1.2 protein. a 2D structure of Nav1.2. Each symbol represents a different variant. Dark blue squares represent variants that differ between humans and other species. Red triangles represent variants associated with ASD (taken from Zhou et al. 2022 and from Sanders et al. 2018). Blue and light blue dots represent variants associated with DEE and SeLNE taken from the ClinVar database, respectively. b, c, d 3D representation of the human Nav1.2-beta2-KIIIA ternary complex (PDB: 6J8E). Colored in green is the β2 subunit, and in beige is the human Nav1.2 protein. Each sphere represents a different variant. b Dark blue spheres: interspecific variation. c Red spheres: ASD variants. d Light blue spheres: DEE/SeLNE variants