AUTHOR=Birolo Giovanni , Benevenuta Silvia , Fariselli Piero , Capriotti Emidio , Giorgio Elisa , Sanavia Tiziana 

TITLE=Protein Stability Perturbation Contributes to the Loss of Function in Haploinsufficient Genes

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.620793

DOI=10.3389/fmolb.2021.620793

ISSN=2296-889X

ABSTRACT=<p>Missense variants are among the most studied genome modifications as disease biomarkers. It has been shown that the “perturbation” of the protein stability upon a missense variant (in terms of absolute ΔΔG value, i.e., |ΔΔG|) has a significant, but not predictive, correlation with the pathogenicity of that variant. However, here we show that this correlation becomes significantly amplified in haploinsufficient genes. Moreover, the enrichment of pathogenic variants increases at the increasing protein stability perturbation value. These findings suggest that protein stability perturbation might be considered as a potential cofactor in diseases associated with haploinsufficient genes reporting missense variants.</p>