The distribution of data in the VEBD across individual proteins was similarly unbalanced. Of the 335 proteins included in the annotated dataset, eight viral and bacterial proteins and one human protein did not include any WT data. However, only three of these (Hepatitis C viral NS3 protease Q0ZMF1 and polyprotein K7XJL6, and Human immunodeficiency virus 1 -HIV-1reverse transcriptase Q9WKE8) had more than 30 bioactivity data points. From the remaining 326 proteins, the vast majority (315) had simultaneously less than 20 variants and less than 10,000 bioactivity data (Figure , Supplementary Table ). Only three human proteins (aldehyde dehydrogenase AL1A1 -P00352, phosphatidylinositol kinase PK3CA -P42336, and epidermal growth factor receptor EGFR -P00533) had more than 10,000 bioactivity data points, of which only one (EGFR) had a variant bioactivity percentage over 2%, specifically 18.36%. Moreover, eight different proteins had more than 20 annotated variants, including WT (Figure ). Some of these variants were single amino acid substitutions, while other variants accumulated several substitutions (Supplementary Table ). The two most tested proteins among these eight with high genetic variance were viral proteins from HIV-1, namely polyprotein RNase H -reverse transcriptase (RNaseH-RT, Q72547) and polyprotein Q72874. The other six were mammalian membrane proteins, some of which may have been subjected to experimental mutagenesis programmes: five class A G protein-coupled receptors (GPCRs)the human gonadotropin-releasing hormone receptor GNRHR (P30968), the rat muscarinic receptor ACM3 (P08483), the human chemokine receptor CXCR4 (P61073), the rat opioid receptor OPRK (P34975), and P2Y1 (P47900)and one solute carrier transporterhuman betaine transporter S6A12 (P48065). The protein with the largest number of annotated variants was GNRHR, with 70 variants other than the WT.