Identification of missense SEPHS1 variants in nine individuals
(A) Schematic of SEPHS1 organization. The blue boxes reflect exons. The yellow box depicts SEPHS1 variant position.
(B) Evolutionary conservation of missense variants observed in SEPHS1. Protein alignment of SEPHS1 orthologs was performed to determine protein sequence conservation of the region of interests. Residues impacted by variants within our cohort are highlighted in red. The Trp352 and Arg371 amino acids are highly conserved from human to frog.
(C) Tolerance Landscape of SEPHS1. The tolerance landscape of SEPHS1 was generated using Metadome (https://stuart.radboudumc.nl/metadome/). The color in the plot is an indication for the tolerance (red, intolerant; blue, tolerant). Graphical representation of the linear protein structure of SEPHS1 with two functional Air Synthase Related Protein domains is below the plot. Missense variants observed in this study are labeled, p.Arg371 and p.Trp352G. The missense variants in SEPHS1 are located in regions that are intolerable for variation (red).