ArticlePloS one2012
Non-silent story on synonymous sites in voltage-gated ion channel genes.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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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.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Heterologous Expression of an Insecticidal Peptide Obtained from the Transcriptome of the Colombian SpiderToxins · 2023Article
- Synonymous nucleotide modification of theThe Journal of biological chemistry · 2018Article
- Cancerouspdomains: comprehensive analysis of cancer type-specific recurrent somatic mutations in proteins and domains.BMC bioinformatics · 2017Article
- Distribution bias analysis of germline and somatic single-nucleotide variations that impact protein functional site and neighboring amino acids.Scientific reports · 2017Article
- Novel dynamin 2 mutations in adult T-cell acute lymphoblastic leukemia.Oncology letters · 2016Article
- Common variable immunodeficiency associated with microdeletion of chromosome 1q42.1-q42.3 and inositol 1,4,5-trisphosphate kinase B (ITPKB) deficiency.Clinical & translational immunology · 2016Article
- Evolutionary Rate Heterogeneity of Primary and Secondary Metabolic Pathway Genes in Arabidopsis thaliana.Genome biology and evolution · 2015Article
- Mutational consequences of aberrant ion channels in neurological disorders.The Journal of membrane biology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synonymous mutations are usually referred to as "silent", but increasing evidence shows that they are not neutral in a wide range of organisms. We looked into the relationship between synonymous codon usage bias and residue importance of voltage-gated ion channel proteins in mice, rats, and humans. We tested whether translationally optimal codons are associated with transmembrane or channel-forming regions, i.e., the sites that are particularly likely to be involved in the closing and opening of an ion channel. Our hypothesis is that translationally optimal codons are preferred at the sites within transmembrane domains or channel-forming regions in voltage-gated ion channel genes to avoid mistranslation-induced protein misfolding or loss-of-function. Using the Mantel-Haenszel procedure, which applies to categorical data, we found that translationally optimal codons are more likely to be used at transmembrane residues and the residues involved in channel-forming. We also found that the conservation level at synonymous sites in the transmembrane region is significantly higher than that in the non-transmembrane region. This study provides evidence that synonymous sites in voltage-gated ion channel genes are not neutral. Silent mutations at channel-related sites may lead to dysfunction of the ion channel.
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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.