In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection

Table 8

ACE2 protein phenotype feature prediction by HOPE analysis.

Residue	Structure	Properties
D427Y		(i) The WT is predicted to be located in its preferred secondary structure, a turn the mutant prefers to be in another secondary structure, therefore the local conformation will be slightly destabilized; (ii) Mutation of the WT into none has the following effect SPD-PSN: slightly inhibits interaction with SARS-CoV spike gp; (iii) The mutation is possibly damaging to the protein
R514G		(i) The mutation introduces a glycine at this position. Glycine is very flexible and can disturb the required rigidity of the protein; (ii) Residues in the vicinity of the mutated residue are annotated in the UniProt as being a binding site; (iii) The mutation could affect the local structure and as a consequence affect the binding site; (iv) The mutation is possibly not damaging to the protein; (v) The mutant is smaller than the WT; this might lead to loss of interaction
R708W		(i) The mutant is more hydrophobic than the WT; (ii) The WT charge was positive, and the mutant charge is neutral; (iii) The mutant is bigger; this might lead to bumps
R710C		(i) The mutant is more hydrophobic than the WT; (ii) The WT is very conserved; (iii) The mutant is smaller; this might lead to loss of interaction
R716C		(i) The mutant is smaller than the WT; (ii) The mutation is located within a stretch of residues annotated in UniProt as a special region: essential of cleavage by TMPRSS11D and TMPRSS2; (iii) The difference in amino acid properties can disturb this region and its function
R768W		(i) The WT is very conserved. In some rare cases, the mutation might occur without damaging the protein; (ii) The mutant is bigger than the WT; this might lead to bumps; (iii) The mutation introduces a more hydrophobic residue at this position; this can result in loss of hydrogen bonds and or disturb correct folding