Details

Autor(en) / Beteiligte

• Giovannetti, Agnese
• Lazzari, Sara
• Mangoni, Manuel
• Traversa, Alice
• Mazza, Tommaso
• Parisi, Chiara
• Caputo, Viviana

Titel

Exploring non-coding genetic variability in ACE2: Functional annotation and in vitro validation of regulatory variants

Ist Teil von

• Gene, 2024-07, Vol.915, p.148422-148422, Article 148422

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •Non-coding variants can have a significant impact on both common and rare diseases.•In silico analysis could identify non-coding variants exerting regulatory effects.•Comprehensive in silico analysis of non-coding variants within the ACE2 gene locus.•Identification of non-coding variants modulating ACE2 function and expression levels. The surge in human whole-genome sequencing data has facilitated the study of non-coding region variations, yet understanding their biological significance remains a challenge. We used a computational workflow to assess the regulatory potential of non-coding variants, with a particular focus on the Angiotensin Converting Enzyme 2 (ACE2) gene. This gene is crucial in physiological processes and serves as the entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 19 (COVID-19). In our analysis, using data from the gnomAD population database and functional annotation, we identified 17 significant Single Nucleotide Variants (SNVs) in ACE2, particularly in its enhancers, promoters, and 3′ untranslated regions (UTRs). We found preliminary evidence supporting the regulatory impact of some of these variants on ACE2 expression. Our detailed examination of two SNVs, rs147718775 and rs140394675, in the ACE2 promoter revealed that these co-occurring SNVs, when mutated, significantly enhance promoter activity, suggesting a possible increase in specific ACE2 isoform expression. This method proves effective in identifying and interpreting impactful non-coding variants, aiding in further studies and enhancing understanding of molecular bases of monogenic and complex traits.