ArticleBiomolecules2020
Protein-Protein Interactions Mediated by Intrinsically Disordered Protein Regions Are Enriched in Missense Mutations.
Article in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Variant characterization in the intrinsically disordered human proteome.Nature structural & molecular biology · 2026Article
- Disordered but Different: Functional and Evolutionary Divergence of Transcription Factor Intrinsically Disordered Regions.bioRxiv : the preprint server for biology · 2026Article
- Impact of intrinsically disordered regions and functional disorder hotspots in the human kinome.Briefings in bioinformatics · 2025Article
- Missense mutations in intrinsically disordered protein regions link pathogenicity and phase separation.The Journal of biological chemistry · 2025Article
- Assessing variant effect predictors and disease mechanisms in intrinsically disordered proteins.PLoS computational biology · 2025Article
- Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.Molecular systems biology · 2024Article
- Pathogenic mutations of human phosphorylation sites affect protein-protein interactions.Nature communications · 2024Article
- Article
- Dynamic nucleolar phase separation influenced by non-canonical function of LIN28A instructs pluripotent stem cell fate decisions.Nature communications · 2024Article
- CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.Nature communications · 2023Article
- Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The intrinsically disordered protein glue of the myelin major dense line: Linking AlphaFold2 predictions to experimental data.Biochemistry and biophysics reports · 2023Article
- Intrinsically Disordered Proteins: An Overview.International journal of molecular sciences · 2022Review
- Does Generic Cyclic Kinase Insert Domain of Receptor Tyrosine Kinase KIT Clone Its Native Homologue?International journal of molecular sciences · 2022Article
- Extended disordered regions of ribosome-associated NAC proteins paralogs belong only to the germline in Drosophila melanogaster.Scientific reports · 2022Article
- Structural dynamics shape the fitness window of alanine:glyoxylate aminotransferase.Protein science : a publication of the Protein Society · 2022Article
- Folding and Intrinsic Disorder of the Receptor Tyrosine Kinase KIT Insert Domain Seen by Conventional Molecular Dynamics Simulations.International journal of molecular sciences · 2021Article
- The Participation of the Intrinsically Disordered Regions of the bHLH-PAS Transcription Factors in Disease Development.International journal of molecular sciences · 2021Article
- The Amazing World of IDPs in Human Diseases.Biomolecules · 2021Article
- Identification of the Primary Factors Determining theSpecificity of Human VKORC1 Recognition by Thioredoxin-Fold Proteins.International journal of molecular sciences · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Because proteins are fundamental to most biological processes, many genetic diseases can be traced back to single nucleotide variants (SNVs) that cause changes in protein sequences. However, not all SNVs that result in amino acid substitutions cause disease as each residue is under different structural and functional constraints. Influential studies have shown that protein-protein interaction interfaces are enriched in disease-associated SNVs and depleted in SNVs that are common in the general population. These studies focus primarily on folded (globular) protein domains and overlook the prevalent class of protein interactions mediated by intrinsically disordered regions (IDRs). Therefore, we investigated the enrichment patterns of missense mutation-causing SNVs that are associated with disease and cancer, as well as those present in the healthy population, in structures of IDR-mediated interactions with comparisons to classical globular interactions. When comparing the different categories of interaction interfaces, division of the interface regions into solvent-exposed rim residues and buried core residues reveal distinctive enrichment patterns for the various types of missense mutations. Most notably, we demonstrate a strong enrichment at the interface core of interacting IDRs in disease mutations and its depletion in neutral ones, which supports the view that the disruption of IDR interactions is a mechanism underlying many diseases. Intriguingly, we also found an asymmetry across the IDR interaction interface in the enrichment of certain missense mutation types, which may hint at an increased variant tolerance and urges further investigations of IDR interactions.
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