ArticleProtein science : a publication of the Protein Society2016
Distribution of single-nucleotide variants on protein-protein interaction sites and its relationship with minor allele frequency.
Article in Protein science : a publication of the Protein Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations.Diabetology & metabolic syndrome · 2025Article
- MTR3D-AF2: Expanding the coverage of spatially derived missense tolerance scores across the human proteome using AlphaFold2.Protein science : a publication of the Protein Society · 2024Article
- An Integrated Computational Analysis of High-Risk SNPs in Angiopoietin-like Proteins (ANGPTL3 and ANGPTL8) Reveals Perturbed Protein Dynamics Associated with Cancer.Molecules (Basel, Switzerland) · 2023Article
- Predicting functional consequences of mutations using molecular interaction network features.Human genetics · 2022Article
- Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection.Genome biology · 2020Article
- Protein-Protein Interactions Mediated by Intrinsically Disordered Protein Regions Are Enriched in Missense Mutations.Biomolecules · 2020Article
- In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract.BMC molecular and cell biology · 2020Article
- PlaPPISite: a comprehensive resource for plant protein-protein interaction sites.BMC plant biology · 2020Article
- AWESOME: a database of SNPs that affect protein post-translational modifications.Nucleic acids research · 2019Article
- Comprehensive Analysis of Constraint on the Spatial Distribution of Missense Variants in Human Protein Structures.American journal of human genetics · 2018Article
- Discrepancies between human DNA, mRNA and protein reference sequences and their relation to single nucleotide variants in the human population.Database : the journal of biological databases and curation · 2016Article
- Structural characterization of single nucleotide variants at ligand binding sites and enzyme active sites of human proteins.Biophysics and physicobiology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent advances in DNA sequencing techniques have identified rare single-nucleotide variants with less than 1% minor allele frequency. Despite the growing interest and physiological importance of rare variants in genome sciences, less attention has been paid to the allele frequency of variants in protein sciences. To elucidate the characteristics of genetic variants on protein interaction sites, from the viewpoints of the allele frequency and the structural position of variants, we mapped about 20,000 human SNVs onto protein complexes. We found that variants are less abundant in protein interfaces, and specifically the core regions of interfaces. The tendency to "avoid" the interfacial core is stronger among common variants than rare variants. As amino acid substitutions, the trend of mutating amino acids among rare variants is consistent in different interfacial regions, reflecting the fact that rare variants result from random mutations in DNA sequences, whereas amino acid changes of common variants vary between the interfacial core and rim regions, possibly due to functional constraints on proteins. This study illustrated how the allele frequency of variants relates to the protein structural regions and the functional sites in general and will lead to deeper understanding of the potential deleteriousness of rare variants at the structural level. Exceptional cases of the observed trends will shed light on the limitations of structural approaches to evaluate the functional impacts of variants.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.