Proteomes 2025, 13(4), 64; https://doi.org/10.3390/proteomes13040064 (registering DOI) - 2 Dec 2025
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Background: Amyloidogenic proteins, a heterogenous group of proteins characterized by their ability to form amyloid fibrils, lead to pathological conditions when they undergo abnormal folding and self-assembly. Missense single-nucleotide polymorphisms (msSNPs) may occur in their sequence, disrupting the normal structure and function of
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Background: Amyloidogenic proteins, a heterogenous group of proteins characterized by their ability to form amyloid fibrils, lead to pathological conditions when they undergo abnormal folding and self-assembly. Missense single-nucleotide polymorphisms (msSNPs) may occur in their sequence, disrupting the normal structure and function of these proteins, pushing them towards amyloidogenesis. Methods: A comprehensive dataset of amyloidogenic proteins was created and their msSNPs were collected and mapped on their amino acid sequence. The chi squared test, logistic regression and the bootstrap method were used to ascertain the statistical significance of the results. Results: The distribution of pathogenic and benign msSNPs highlighted the predicted amyloidogenic segments as hotspots for pathogenic msSNPs. Analysis of the change in residue properties and pathogenicity status revealed that the substitution of negatively charged residues by any other type of residue tends to be pathogenic. Furthermore, certain substitutions were found to be more likely pathogenic than average. Additionally, a case study of APP, a key protein in Alzheimer’s disease, is used as an example. Conclusions: This study will hopefully showcase the importance of amyloidogenic protein msSNPs as well as spark an interest in research of the mechanisms that lead to the formation of amyloid deposits under the scope of pathogenic msSNPs.
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