Fig. 4

Depletion of rare, heterozygous LOF variants in regions mapping to protein domains. We plotted scaled protein domain depletion scores for each domain mapping within a gene; high scaled scores indicate that a protein domain is depleted of rare (MAF < 0.5%) mutations compared to the rest of the gene. Darkened points above the red dashed line represent protein domains that are significantly depleted of mutations after correcting for the number of genes remaining after filtering. Larger points indicate protein domains with a greater length in proportion to the transcript length. Points are colored if the protein domain is within a gene that is an essential human gene or is causal for a Mendelian disorder. Abbreviations: AD, autosomal dominant. AR, autosomal recessive. XL, X-linked