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Open AccessArticle

Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy

1
Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia
2
Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, 450000 Ufa, Russia
3
Medical Institute, North-Eastern Federal University, 677000 Yakutsk, Russia
4
Medical-Psychological-Social Institute, Katanov State University of Khakassia, 655017 Abakan, Russia
5
Laboratory of Genomic Medicine, Dagestan State Medical University, 367000 Makhachkala, Russia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2021, 12(1), 19; https://doi.org/10.3390/genes12010019
Received: 16 November 2020 / Revised: 18 December 2020 / Accepted: 21 December 2020 / Published: 25 December 2020
(This article belongs to the Section Molecular Genetics and Genomics)
The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene–gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy. View Full-Text
Keywords: TMPRSS2; ACE2; BSG; COVID-19; SARS-CoV-2; SNV; expression; pharmacotranscriptomics TMPRSS2; ACE2; BSG; COVID-19; SARS-CoV-2; SNV; expression; pharmacotranscriptomics
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MDPI and ACS Style

Zarubin, A.; Stepanov, V.; Markov, A.; Kolesnikov, N.; Marusin, A.; Khitrinskaya, I.; Swarovskaya, M.; Litvinov, S.; Ekomasova, N.; Dzhaubermezov, M.; Maksimova, N.; Sukhomyasova, A.; Shtygasheva, O.; Khusnutdinova, E.; Radzhabov, M.; Kharkov, V. Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy. Genes 2021, 12, 19. https://doi.org/10.3390/genes12010019

AMA Style

Zarubin A, Stepanov V, Markov A, Kolesnikov N, Marusin A, Khitrinskaya I, Swarovskaya M, Litvinov S, Ekomasova N, Dzhaubermezov M, Maksimova N, Sukhomyasova A, Shtygasheva O, Khusnutdinova E, Radzhabov M, Kharkov V. Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy. Genes. 2021; 12(1):19. https://doi.org/10.3390/genes12010019

Chicago/Turabian Style

Zarubin, Aleksei; Stepanov, Vadim; Markov, Anton; Kolesnikov, Nikita; Marusin, Andrey; Khitrinskaya, Irina; Swarovskaya, Maria; Litvinov, Sergey; Ekomasova, Natalia; Dzhaubermezov, Murat; Maksimova, Nadezhda; Sukhomyasova, Aitalina; Shtygasheva, Olga; Khusnutdinova, Elza; Radzhabov, Magomed; Kharkov, Vladimir. 2021. "Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy" Genes 12, no. 1: 19. https://doi.org/10.3390/genes12010019

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