Fig. 4

Visualization of para_zscores for KCNQ2, STXBP1, CACNA1A, and GRIN2B. Protein sequence is plotted from left to right. Each bar and dot represent one amino acid. Amino acids affected by a missense mutation in the NDD cohort are colored blue, patient PTVs are depicted in pink, and synonymous variants in orange. Amino acid residues with no mutations are colored gray. y-axis: para_zscore. Positive values indicate paralog conservation, and the highest score indicates that these amino acids are identical over all gene family members. The red dotted lines indicate the mean paralog conservation of each protein sequence, and the bars below the mean indicate regions of low paralog conservation, thus higher sequence variability over all members of the gene family