Fig. 2

Rare coding variation in GPR68 is associated with risk of chemotherapy-induced peripheral neuropathy. a Cumulative incidence plot showing the association between the burden of rare coding variants in GPR68 and time-to-PN event in all trial arms. Shaded regions designate the 95% confidence interval around the cumulative incidence curves. b Lollipop plot of rare coding variants in GPR68 that were used for burden testing with time-to-PN event in the entire clinical trial cohort. The y-axis of the plot provides the number of patients that carried the rare coding variant as designated by rsID and coding sequence consequence along the top of the plot. rs61745750 (330 K > 330N) and truncating variant rs61745752 (336E > 336*) is highlighted by the blue square. c Protein plot illustrating the trans-membrane domains of GPR68 as well as the position of rs61745750 (330 K > 330N) highlighted in blue and rs61745752 (336E > 336*) highlighted in red on the C-terminus of the protein. d Gray squares illustrate amino acids starting at position 290 in GPR68 interspersed with purple squares that designate predicted phosphorylation sites. Complete arrestin binding motif matches shown in the first row of blue squares. Partial motif matches are shown in peach color below where darker squares correspond to amino acids involved in more binding motifs. The position of rs61745750 (330 K > 330N) is highlighted in blue and rs61745752 (336E > 336*) truncation is highlighted in red. Positions and sequence of the motif matches are provided in the table where PL = partial long, PS = partial short, L = complete long. The lysine substituted by asparagine is shown across motif matches in purple. Motifs removed by rs61745752 (336E > 336*) are highlighted in red