Table 1.
Summary of reported ACE2 variants and possible interactions with SARS‐CoV‐2
| Variants | Main findings | Population | References |
|---|---|---|---|
| S19P I21V, I21T, E23K, A25T, K26R, T27A, E35D, N64K, E75G, T92I, Q102P, H378R | *Interaction booster between ACE2 and S1 protein, | Europeans, Africans, Asians, Americans | Darbani (2020) |
| *H378R and S19P were specific variants of Europeans and Africans | |||
| E35K, E37K, Y50F, N51D, N51S, M62V, K68E, F72V, M82I, G326E, E329G, G352V, D355N, Q388L, P389H, H505R, R514G/*, Y515C | *Interaction‐inhibitor variants, | ||
| *Q388L and M82I were found as specific variants of Americans and Africans | |||
| R219C, R219H, M383T, P389H, D427Y, R514G, R708W, R710C, R710H, R716C, L731F, R768W | *Distribution of deleterious variants differs among populations | 81,000 genomes AFR, AMI, AMR, ASJ, EAS, EUR, FIN, SAS | Hou et al. (2020) |
| *39% (24/61) and 54% (33/61) of deleterious variants occur in AFR and EUR populations, | |||
| *Prevalence of deleterious variants among AMR, EAS, FIN, and SAS populations is 2%–10% | |||
| N720D | *N720D variant impacted the stability and flexibility of ACE2, | Not specified | Mohammad et al. (2020) |
| resulting in a more favorable site for TMPRSS2 binding and cleavage. | |||
| S19P, E329G | *S19P, K26E, and M82I may adversely affect the stability of the encoded protein | Not specified | Hussain et al. (2020) |
| *S19P and E329G showed noticeable variations in their intermolecular interactions with the S protein, which may confer resistance against the SARS‐CoV‐2 attachment | |||
| K26R | *Mutated more frequently in NFE, | 56.885 NFE versus 9.197 EAS | Li et al. (2020) |
| *Increases the binding free energy, slightly decreases the binding affinity | |||
| I468V | *Mutated more frequently in EAS, | ||
| *Increases the binding free energy, slightly decreases the binding affinity | |||
| N720D, K26R, G211R | *Predicted to interfere with protein structure and stabilization | 6930 Italian | Benetti et al. (2020) |
| L351V, P389H | *Predicted to interfere with SARS‐CoV‐2 spike protein binding | ||
| K26R, I21V, E23K, T27A, N64K, T92I, Q102P, H378R, S19P | *Predicted to increase susceptibility | 290,000 samples, >400 population groups | Stawiski et al. (2020) |
| K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L, D509Y | *Putative protective variants predicted to show decreased binding to S‐protein | ||
| c.439+4G>A intronic, N630H, N720D | *3 germline variants identified in Covid‐19 patients | 131 Covid‐19, 1000 control | Novelli et al. (2020) |
| *There is no association of ACE2 variants with Covid‐19 severity | |||
| K26R | * Most frequent in the ASJ, lowest in the Asian populations | African, AAF, American, ASJ, Asian, EUR and Latino. | (Ali et al., 2020) |
| *Causes a decrease in the binding energies by approximately 2.1 kcal/mol | |||
| I468V, R219C, K341R, D206G, G211R | * Increases the electrostatic attraction ordered by binding strength from weakest to strongest. | ||
| *Variants are most frequent in EAS, SAS, AAF, EUR, and SAS populations, respectively. | |||
| H378R | *Directly weakens the binding of catalytic metal atom to decrease ACE2 activity | n = 141,456 Not specified | (Guo et al., 2020) |
| S19P | *Distorts the most important helix to the S‐protein | ||
| G211R, N206G, R219C, R219H, K341R, I468V, S547C | *May affect secondary structures | ||
| G405E, W461R, F588S | *Predicted as highly destabilizing to the structure of the bound complex. | Not specified | (Khalid & Naveed, 2020) |
Abbreviations: ACE2, angiotensin‐converting enzyme‐2; AFR, African/African American; AMI, Amish; AMR, Latino/Admixed American; ASJ, Ashkenazi Jewish; EAS, East Asians; EUR, European; FIN, Finnish; NFE, Non‐Finnish European; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; SAS, South Asian.