Genetic variations in the human severe acute respiratory syndrome coronavirus receptor ACE2 and serine protease TMPRSS2.

Journal of Clinical Pathology
Kohei Fujikura, Kazuma Uesaka

Abstract

The recent emergence of novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health emergency. The coronaviral entry requires the spike (S)-protein for attachment to the host cell surface, and employs human angiotensin-converting enzyme 2 (hACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S-protein priming. Although coronaviruses undergo evolution by mutating themselves, it is also essential to know the host genetic factors. Here, we describe the single nucleotide variations (SNVs) in human ACE2 and TMPRSS2. The genetic variants derived from five population-sequencing projects were classified by variant type, allele frequency (AF), ethnic group and estimated pathogenicity. The SNVs in SARS-CoV-2/hACE2 contact residues were investigated. The genetic variability was normalised using non-linear regression and the total number of SNVs was estimated by the derived formulas. We detected 349 and 551 SNVs in ACE2 and TMPRSS2, respectively, in a total of 156 513 individuals. The vast majority (>97%) of the SNVs were very rare (AF <0.1%) and population-specific, and were computationally estimated to be more frequently deleterious than the SNVs with high AF. These SNVs were distrib...Continue Reading

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Citations

Nov 26, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Girish PathangeyAmr E Abbas
May 22, 2021·European Journal of Medical Research·SeyedAhmad SeyedAlinaghiFabricio Voltarelli
Aug 3, 2021·Virus Research·Filipa F ValeJoao Goncalves

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Methods Mentioned

BETA
genotyping

Software Mentioned

MKL
PROVEAN
DANN
GERP
MutationAssessor
DEOGEN2
PhyloP
JMP
SIFT4G
VEST4

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