ArticleProteins2011
A missense mutation in CLIC2 associated with intellectual disability is predicted by in silico modeling to affect protein stability and dynamics.
Article in Proteins, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- The role of SKA2 on affective disorder, post-traumatic stress disorder and suicide behavior: systematic review and in silico analysis.Metabolic brain disease · 2024Pooled it
- Electrostatics and disease: Large-scale assessment of human missense variants causing protein charge alterations and their implications for disease.Biophysical journal · 2026Article
- X-Linked Muscular Dystrophy in a Cat with a Putative Variant in theAnimals : an open access journal from MDPI · 2026Article
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- Prediction of the most deleterious non-synonymous SNPs in the human IL1B gene: evidence from bioinformatics analyses.BMC genomic data · 2024Article
- An in-silico analysis of OGT gene association with diabetes mellitus.BMC research notes · 2024Article
- Most Monogenic Disorders Are Caused by Mutations Altering Protein Folding Free Energy.International journal of molecular sciences · 2024Article
- A comprehensive in silico investigation into the pathogenic SNPs in the RTEL1 gene and their biological consequences.PloS one · 2024Article
- In Silico Evaluation of Coding and Non-Coding nsSNPs in the Thrombopoietin Receptor (Current issues in molecular biology · 2023Article
- In silico prediction of deleterious non-synonymous SNPs inAsian biomedicine : research, reviews and news · 2023Article
- Discovering Deleterious Single Nucleotide Polymorphisms of Human AKT1 Oncogene: An In Silico Study.Life (Basel, Switzerland) · 2023Article
- Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome.Human genetics · 2023Article
- Comprehensive In Silico Characterization of the Coding and Non-Coding SNPs in HumanDiagnostics (Basel, Switzerland) · 2023Article
- Assessing Variants of Uncertain Significance Implicated in Hearing Loss Using a Comprehensive Deafness Proteome.Research square · 2023Article
- Evaluation of AlphaFold structure-based protein stability prediction on missense variations in cancer.Frontiers in genetics · 2023Article
- Article
- Review
- Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure.Nature communications · 2022Article
- Solvent accessibility of E1α and E1β residues with known missense mutations causing pyruvate dehydrogenase complex (PDC) deficiency: Impact on PDC-E1 structure and function.Journal of inherited metabolic disease · 2022Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Large-scale next generation resequencing of X chromosome genes identified a missense mutation in the CLIC2 gene on Xq28 in a male with X-linked intellectual disability (XLID) and not found in healthy individuals. At the same time, numerous nsSNPs (nonsynonomous SNP) have been reported in the CLIC2 gene in healthy individuals indicating that the CLIC2 protein can tolerate amino acid substitutions and be fully functional. To test the possibility that p.H101Q is a disease-causing mutation, we performed in silico simulations to calculate the effects of the p.H101Q mutation on CLIC2 stability, dynamics, and ionization states while comparing the effects obtained for presumably harmless nsSNPs. It was found that p.H101Q, in contrast with other nsSNPs, (a) lessens the flexibility of the joint loop which is important for the normal function of CLIC2, (b) makes the overall 3D structure of CLIC2 more stable and thus reduces the possibility of the large conformational change expected to occur when CLIC2 moves from a soluble to membrane form, and (c) removes the positively charged residue, H101, which may be important for the membrane association of CLIC2. The results of in silico modeling, in conjunction with the polymorphism analysis, suggest that p.H101Q may be a disease-causing mutation, the first one suggested in the CLIC family.
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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.