scholarly journals Impacts of Nonsynonymous Single Nucleotide Polymorphisms of Adiponectin Receptor 1 Gene on Corresponding Protein Stability: A Computational Approach

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Md. Abu Saleh ◽  
Md. Solayman ◽  
Sudip Paul ◽  
Moumoni Saha ◽  
Md. Ibrahim Khalil ◽  
...  
Keyword(s):  
Free Energy ◽  
Single Nucleotide Polymorphisms ◽  
Metabolic Diseases ◽  
Gene Mutations ◽  
Adiponectin Receptor ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Adiponectin Receptor 1 ◽  
Structural Impacts ◽  
Dbsnp Database

Despite the reported association of adiponectin receptor 1 (ADIPOR1)gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the humanADIPOR1at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs ofADIPOR1gene listed in the dbSNP database. Ourin silicoanalysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs ofADIPOR1gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1.

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

In Silico Analysis of Non Synonymous Single Nucleotide Polymorphisms (nsSNPs) of SMPX Gene in Hearing Impairment

2018 ◽  
Author(s):  
Md. Arifuzzaman ◽  
Sarmistha Mitra ◽  
Amir Hamza ◽  
Raju Das ◽  
Nurul Absar ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Protein Stability ◽  
In Silico Analysis ◽  
Normal Activity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Binding Motifs ◽  
Stability Change ◽  
And Function ◽  
Dbsnp Database

ABSTRACTBackgroundMutations in SMPX gene can disrupt the normal activity of the SMPX protein which is involved in hearing process.ObjectiveIn this study, deleterious non-synonymous single nucleotide polymorphisms were isolated from the neutral variants by using several bioinformatics tools.MethodFirstly, dbSNP database hosted by NCBI was used to retrieve the SNPs of SMPX gene, secondly, SIFT was used primarily to screen the damaging SNPs. Further, for validation PROVEAN, PredictSNP and PolyPhen 2 were used. I-Mutant 3 was utilized to analyze the protein stability change and MutPred predicted the molecular mechanism of protein stability change. Finally evolutionary conservation was done to study their conservancy by using ConSurf server.ResultsA total of 26 missense (0.6517%) and 3 nonsense variants (0.075%) were retrieved and among them 4 mutations were found deleterious by all the tools of this experiment and are also highly conserved according to ConSurf server. rs772775896, rs759552778, rs200892029 and rs1016314772 are the reference IDs of deleterious mutations where the substitutions are S71L, N19D, A29T and K54N. Loss of Ubiquitination, loss of methylation, loss of glycosylation, and loss of MoRF binding motifs are the root causes of protein stability change.ConclusionThis is the first study regarding nsSNPs of SMPX gene where the most damaging SNPs were screened that are associated with the SMPX gene and can be used for further research to study their effect on protein structure and function, their dynamic behavior and how they actually affect protein’s flexibility.

scholarly journals ParkinExon Rearrangements and Sequence Variants inLRRK2Mutations Carriers: Analysis on a Possible Modifier Effect onLRRK2Penetrance

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Paolo Solla ◽  
Antonino Cannas ◽  
Gianluca Floris ◽  
Maria Rita Murru ◽  
Daniela Corongiu ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Single Nucleotide Polymorphisms ◽  
Family Members ◽  
Gene Mutations ◽  
Sequence Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mutation Carriers ◽  
Common Causes ◽  
Modifier Effect

Mutations inLRRK2represent the most common causes of Parkinson's disease (PD) identified to date, but their penetrance is incomplete and probably due to the presence of other genetic or environmental factors required for development of the disease. We analyzed the presence ofparkinsequence variants (mutations or polymorphisms) and exon rearrangements inLRRK2mutations carriers (both PD patients and unaffected relatives) in order to detect a possible modifier effect on penetrance. Eight families with nine PD patients with heterozygousLRRK2mutations (identified within 380 Sardinian PD patients screened for the presence of the five most commonLRRK2mutations) and sixteen additional relatives were genetically investigated for the presence ofLRRK2andparkinmutations. No evidence was found for the presence of pathologicalparkinmutations or exon rearrangements in patients or not affected family members. Three single-nucleotide polymorphisms (SNPs) were identified both in patients and unaffected relatives but did not significantly differ between the two groups. These data provide no support to the hypothesis whereby suchparkingene mutations may be commonly implicated in possible effect on penetrance inLRRK2mutation carriers.

ACTN4 Gene Mutations and Single Nucleotide Polymorphisms in Idiopathic Focal Segmental Glomerulosclerosis

2009 ◽  
Vol 111 (2) ◽  
pp. c87-c94 ◽  
Author(s):  
Shengchuan Dai ◽  
Zhaohui Wang ◽  
Xiaoxia Pan ◽  
Xiaonong Chen ◽  
Weiming Wang ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Focal Segmental Glomerulosclerosis ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Segmental Glomerulosclerosis
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