Fig. 2: The landscape of genetic variability in major drug-metabolizing CYP genes.

a Across 141,614 individuals, a total of 10,176 genetic variants were identified 6016 of which were exonic. Pie charts indicate the distribution of exonic variants across variant classes. b The majority of exonic variants have MAFs < 1% (98.8%) or <0.1% (96.8%). c Stacked column plot showing the number of identified exonic variants for each analyzed CYP gene (left y-axis). White dots indicate the number of variants per base pair (bp; right y-axis). All variants were categorized into deleterious (red) or neutral (green) using the ADME Prediction Framework (see Methods). The fraction of putatively deleterious variants (including both reduced function and loss-of-function variants) for each CYP gene is shown. A list of all putatively deleterious variants and their estimated activity scores is provided in Supplementary Table 2. d Functional contribution of star alleles and non-star alleles to the overall functional variability of CYP genes. Black numbers indicate the aggregated frequencies of functional star alleles and non-star alleles. The ratio of the genetically encoded functional variability allotted to non-star alleles and star alleles is indicated by the red percentage values. e Functional contribution of non-star alleles to the population-specific functional variability of CYP genes. Only the top 5 and bottom 5 gene-population pairs are shown. All population-specific contributions of non-star alleles are shown in Supplementary Table 3. AFR African, EAS East Asian, SAS South Asian, AMR admixed Americans, FIN Finnish, AJ Ashkenazi Jewish, MAF minor allele frequency, UTR untranslated region.