Fig. 3.

The C. elegans MatchVars for human IFT140^P726A but not IFT140^G704S displays defects in the lipophilic fluorescent dye uptake in the head and tail. a) Clinical significance and disease relevance from ClinVar, frequency from gnomAD, SIFT, and PolyPhen2 score were presented for two human variants, P726A and G704S. MSS stands for Mainzer–Saldino syndrome. b) The positions of these two variants were shown on the MSA of IFT140 orthologs from 13 different species. The conservation of the corresponding amino acid position across the 13 species is depicted by the blue bars at the bottom of the plot. The extended versions of MSAs were provided as supplementary files. c) The positions of human P726A and G704S variants and C. elegans P702A and G680S variants were shown in a lollipop plot of IFT140 proteins from humans and C. elegans, respectively. The P702A and G680S are MatchVars of the human P726A and G704S in human IFT140, respectively. Clinical significance (VUS and conflicted) for human variants from ClinVar were presented. d) The entire worms, including heads and tails, were depicted in the C. elegans representative drawing. The fluorescence images were displayed alongside representative sketches of the head and tail cells. White indicates no dye uptake in the head and tail, while red indicates dye uptake in the cells. After the fluorescent dye assay, fluorescent images of the wild type and the indicated mutants were shown. ift-140(lf) and ift-140^P702A mutants were Dye negative in the head and tails. The expression of ift-140 completely restored the dye uptake failure of ift-140^P702A mutants. Scale bar: 10 μm.