Fig. 1. The genetic landscape of human drug targets.

(A) After exclusion of drugs with nonprotein or nonhuman targets or drugs targeting only specific somatic mutations, we obtained 606 genes encoding the target proteins of 1155 FDA-approved drugs, resulting in a total of 3346 unique drug-target pairs. (B) The analyzed drugs were distributed across anatomical therapeutic chemical (ATC) classifications. The most common targets were enzymes and ion channels followed by membrane receptors and structural components. (C) Column plot showing the number of target encoding genes per drug. (D) Across 138,632 individuals, we identified a total of 798,842 variants of which 479,860 were exonic. Using stringent computational assessments of pathogenicity (see Materials and Methods), 82,884 variants were identified as putatively deleterious. (E) The majority of exonic variants in drug target genes are rare with minor allele frequency (MAF) <1%. (F) Variant numbers differed >100-fold between drug targets, primarily because of differences in gene length (R² = 0.87). Confidence bands (95%) are shown in yellow. The gene density distributions for gene length and variant number are shown across the different protein classes as histograms on top and on the right of the scatter plot, respectively.