ArticleNucleic acids research2010
Using protein design algorithms to understand the molecular basis of disease caused by protein-DNA interactions: the Pax6 example.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 63 citations in OpenAlex.
- Article
- The Systemic Genotype-Phenotype Characterization of PAX6-Related Eye Disease in 164 Chinese Families.Investigative ophthalmology & visual science · 2024Article
- An Unusual Presentation of Novel Missense Variant inCurrent issues in molecular biology · 2023Article
- ChromDL: A Next-Generation Regulatory DNA Classifier.bioRxiv : the preprint server for biology · 2023Article
- Article
- Whole-genome sequencing of multiple related individuals with type 2 diabetes reveals an atypical likely pathogenic mutation in the PAX6 gene.European journal of human genetics : EJHG · 2023Article
- Phenotypic spectrum and genetics of PAX2-related disorder in the Chinese cohort.BMC medical genomics · 2021Article
- Protein structural features predict responsiveness to pharmacological chaperone treatment for three lysosomal storage disorders.PLoS computational biology · 2021Article
- Integrating genome sequence and structural data for statistical learning to predict transcription factor binding sites.Nucleic acids research · 2020Article
- Identification of pathogenic missense mutations using protein stability predictors.Scientific reports · 2020Article
- FoldX 5.0: working with RNA, small molecules and a new graphical interface.Bioinformatics (Oxford, England) · 2019Article
- Functional reassessment of PAX6 single nucleotide variants by in vitro splicing assay.European journal of human genetics : EJHG · 2019Article
- Congenital Adrenal Hyperplasia (CAH) due to 21-Hydroxylase Deficiency: A Comprehensive Focus on 233 Pathogenic Variants of CYP21A2 Gene.Molecular diagnosis & therapy · 2018Review
- Article
- Pathogenic mutations in retinitis pigmentosa 2 predominantly result in loss of RP2 protein stability in humans and zebrafish.The Journal of biological chemistry · 2017Article
- Structure-based activity prediction of CYP21A2 stability variants: A survey of available gene variations.Scientific reports · 2016Article
- Structure-based prediction of transcription factor binding specificity using an integrative energy function.Bioinformatics (Oxford, England) · 2016Article
- Article
- Structure-based modeling of protein: DNA specificity.Briefings in functional genomics · 2015Review
- UniPROBE, update 2015: new tools and content for the online database of protein-binding microarray data on protein-DNA interactions.Nucleic acids research · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Quite often a single or a combination of protein mutations is linked to specific diseases. However, distinguishing from sequence information which mutations have real effects in the protein's function is not trivial. Protein design tools are commonly used to explain mutations that affect protein stability, or protein-protein interaction, but not for mutations that could affect protein-DNA binding. Here, we used the protein design algorithm FoldX to model all known missense mutations in the paired box domain of Pax6, a highly conserved transcription factor involved in eye development and in several diseases such as aniridia. The validity of FoldX to deal with protein-DNA interactions was demonstrated by showing that high levels of accuracy can be achieved for mutations affecting these interactions. Also we showed that protein-design algorithms can accurately reproduce experimental DNA-binding logos. We conclude that 88% of the Pax6 mutations can be linked to changes in intrinsic stability (77%) and/or to its capabilities to bind DNA (30%). Our study emphasizes the importance of structure-based analysis to understand the molecular basis of diseases and shows that protein-DNA interactions can be analyzed to the same level of accuracy as protein stability, or protein-protein interactions.
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.