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Updated: Aug 26, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Pathogenic variation types in human genes relate to diseases through Pfam and InterPro mapping
Giulia Babbi1, Castrense Savojardo1, Davide Baldazzi2
1Biocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Abstract:
Grouping residue variations in a protein according to their physicochemical properties allows a dimensionality reduction of all the possible substitutions in a variant with respect to the wild type. Here, by using a large dataset of proteins with disease-related and benign variations, as derived by merging Humsavar and ClinVar data, we investigate to which extent our physicochemical grouping procedure can help in determining whether patterns of variation types are related to specific groups of diseases and whether they occur in Pfam and/or InterPro gene domains. Here, we download 75,145 germline disease-related and benign variations of 3,605 genes, group them according to physicochemical categories and map them into Pfam and InterPro gene domains. Statistically validated analysis indicates that each cluster of genes associated to Mondo anatomical system categorizations is characterized by a specific variation pattern. Patterns identify specific Pfam and InterPro domain-Mondo category associations. Our data suggest that the association of variation patterns to Mondo categories is unique and may help in associating gene variants to genetic diseases. This work corroborates in a much larger data set previous observations from our group.
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