ArticleHuman mutation2010
In silico functional profiling of human disease-associated and polymorphic amino acid substitutions.
Article in Human mutation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Predicting interaction-specific protein-protein interaction perturbations by missense variants with MutPred-PPI.bioRxiv : the preprint server for biology · 2026Article
- Literature-driven extraction and computational prediction of causal statements linking genetic variants to biological processes, pathways and phenotypes.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2026Article
- Gene-based calibration of high-throughput functional assays for clinical variant classification.bioRxiv : the preprint server for biology · 2025Article
- Deep learning tools predict variants in disordered regions with lower sensitivity.BMC genomics · 2025Article
- Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers.Human genetics · 2025Article
- Prediction of protein structure and AI.Journal of human genetics · 2024Review
- Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers.Research square · 2024Article
- Evolutionary and functional lessons from human-specific amino acid substitution matrices.NAR genomics and bioinformatics · 2021Article
- Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.Scientific reports · 2021Article
- IDRMutPred: predicting disease-associated germline nonsynonymous single nucleotide variants (nsSNVs) in intrinsically disordered regions.Bioinformatics (Oxford, England) · 2020Article
- OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation.Nature communications · 2020Article
- Pathogenicity and functional impact of non-frameshifting insertion/deletion variation in the human genome.PLoS computational biology · 2019Article
- Precision Profiling of the Cardiovascular Post-Translationally Modified Proteome: Where There Is a Will, There Is a Way.Circulation research · 2018Review
- Missense variant pathogenicity predictors generalize well across a range of function-specific prediction challenges.Human mutation · 2017Article
- Landscape of Pleiotropic Proteins Causing Human Disease: Structural and System Biology Insights.Human mutation · 2017Article
- Interpreting functional effects of coding variants: challenges in proteome-scale prediction, annotation and assessment.Briefings in bioinformatics · 2016Review
- Protein function in precision medicine: deep understanding with machine learning.FEBS letters · 2016Review
- Generalized enrichment analysis improves the detection of adverse drug events from the biomedical literature.BMC bioinformatics · 2016Article
- The Contribution of Missense Mutations in Core and Rim Residues of Protein-Protein Interfaces to Human Disease.Journal of molecular biology · 2015Article
- Global human frequencies of predicted nuclear pathogenic variants and the role played by protein hydrophobicity in pathogenicity potential.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
An important challenge in translational bioinformatics is to understand how genetic variation gives rise to molecular changes at the protein level that can precipitate both monogenic and complex disease. To this end, we compiled datasets of human disease-associated amino acid substitutions (AAS) in the contexts of inherited monogenic disease, complex disease, functional polymorphisms with no known disease association, and somatic mutations in cancer, and compared them with respect to predicted functional sites in proteins. Using the sequence homology-based tool SIFT to estimate the proportion of deleterious AAS in each dataset, only complex disease AAS were found to be indistinguishable from neutral polymorphic AAS. Investigation of monogenic disease AAS predicted to be nondeleterious by SIFT were characterized by a significant enrichment for inherited AAS within solvent accessible residues, regions of intrinsic protein disorder, and an association with the loss or gain of various posttranslational modifications. Sites of structural and/or functional interest were therefore surmised to constitute useful additional features with which to identify the molecular disruptions caused by deleterious AAS. A range of bioinformatic tools, designed to predict structural and functional sites in protein sequences, were then employed to demonstrate that intrinsic biases exist in terms of the distribution of different types of human AAS with respect to specific structural, functional and pathological features. Our Web tool, designed to potentiate the functional profiling of novel AAS, has been made available at http://profile.mutdb.org/.
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