In Silico Identification and Functional Impact of Deleterious Nonsynonymous Single‐Nucleotide Polymorphisms (nsSNPs) in Type 2 Diabetes–Associated Genes in South Asian Populations DOI Creative Commons
Md. Hafizur Rahman, Md. Numan Islam,

Md. Golam Rabby

et al.

Genetics Research, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

This study explores the impact of nonsynonymous single‐nucleotide polymorphisms (nsSNPs) on type 2 diabetes (T2D). The nsSNPs are genetic variations that alter amino acids within proteins, affecting protein structure and function. investigated seven candidate genes associated with T2D pathogenesis from genome‐wide association studies (GWASs) catalog datasets. Subsequently, six mutation‐prediction tools were employed to identify most harmful these genes. Further analysis involved evaluating evolutionary conservation using ConSurf server assessing stability I‐Mutant MUpro. Functional structural effects predicted MutPred2, Project HOPE, FoldAmyloid tools. We obtained 42 deleterious identified Among these, 38 located in highly conserved residues a conservative score 7–9. Furthermore, 20 found decrease stability, 18 them classified as pathogenic mutations. These mutations can either reduce or increase size charge hydrophobic characteristics affected proteins. In addition, eight mutants four amyloidogenic regions, suggesting potential link aggregation. findings provide valuable insights into physicochemical properties changes nsSNPs. concludes distinctive significant suggest for future research. Understanding variants through large‐scale may pave way developing therapeutic interventions targeting variations, ultimately improving our understanding treatment.

Language: Английский

Evaluation of single nucleotide polymorphisms in the human norepinephrine transporter (hNET) gene for structural, functional, and pathogenic significance DOI
Orçun Avşar

Nucleosides Nucleotides & Nucleic Acids, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Jan. 6, 2025

The norepinephrine transporter (NET) is a key regulator of noradrenergic neurotransmission and homeostasis, regulating the levels in brain peripheral tissues. hNET major target neuropsychiatric disorders such as depressive disorder, autonomic dysfunction, attention deficit hyperactivity disorder (ADHD). human gene (hNET, SLC6A2) contains 504 missense single nucleotide polymorphisms (SNPs). These SNPs have been identified public databases. Elucidating molecular effects on protein function structure may provide insight into how affect biological activity contribute to etiopathogenesis disease. Therefore, our study, we aimed analyze structural, functional, pathogenic genetic variants SLC6A2 using various bioinformatics tools. In rs45564432 (T283R), rs121918126 (A457P), rs5558 (F528C), rs5566 (A369P), rs13306041 (R121Q), rs147833183 (R301H), rs201263363 (Y294H), rs201586185 (A369V), rs373891109 (T258I) with structural functional effects. Our results demonstrated significance high-risk protein. We anticipate that this study will future experimental studies investigating relationship between pathogenesis treatment disorders.

Language: Английский

Citations

1
Investigating the functional and structural effect of non-synonymous single nucleotide polymorphisms in the cytotoxic T-lymphocyte antigen-4 gene: An in-silico study DOI Creative Commons
Md. Mostafa Kamal,

Kazi Fahmida Haque Shantanu,

Shamiha Tabassum Teeya

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0316465 - e0316465

Published: Jan. 24, 2025

The cytotoxic T-lymphocyte antigen-4 (CTLA4) is essential in controlling T cell activity within the immune system. Thus, uncovering molecular dynamics of single nucleotide polymorphisms (SNPs) CTLA4 gene critical. We identified non-synonymous SNPs (nsSNPs), examined their impact on protein stability, and sequences associated with them human gene. There were 3134 (rsIDs) our study. Out these, 186 missense variants (5.93%), 1491 intron (47.57%), 91 synonymous (2.90%), while remaining unspecified. utilized SIFT, PolyPhen-2, PROVEAN, SNAP for identifying deleterious nsSNPs, SNPs&GO, PhD SNP, PANTHER verifying risk nsSNPs Following SIFT analysis, six as reporting second third probably damaging one benign, respectively. From upstream rs138279736, rs201778935, rs369567630, rs376038796 found to be deleterious, damaging, disease associated. ConSurf predicted conservation scores four Project Hope suggested that all mutations could disrupt interactions. Furthermore, mCSM DynaMut2 analyses indicated a decrease ΔΔG stability mutants. GeneMANIA STRING networks highlighted correlations CD86 CD80 genes. Finally, MD simulation revealed consistent fluctuation RMSD RMSF, consequently Rg, hydrogen bonds, PCA mutant proteins compared wild-type, which might alter functional structural protein. current comprehensive study shows how various can modify characteristics protein, potentially influencing pathogenesis diseases humans. Further, experimental studies are needed analyze effect these susceptibility pathological phenotype populations.

Language: Английский

Citations

1
Genome-wide exploration: evolution, structural characterization, molecular docking, molecular dynamics simulations and expression analysis of sugar transporter (ST) gene family in potato (Solanum tuberosum) DOI
Md. Sohel Mia,

Sourav Biswas Nayan,

Md. Numan Islam

et al.

Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: 117, P. 108402 - 108402

Published: March 1, 2025

Language: Английский

Citations

0
In Silico Identification and Functional Impact of Deleterious Nonsynonymous Single‐Nucleotide Polymorphisms (nsSNPs) in Type 2 Diabetes–Associated Genes in South Asian Populations DOI Creative Commons
Md. Hafizur Rahman, Md. Numan Islam,

Md. Golam Rabby

et al.

Genetics Research, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

This study explores the impact of nonsynonymous single‐nucleotide polymorphisms (nsSNPs) on type 2 diabetes (T2D). The nsSNPs are genetic variations that alter amino acids within proteins, affecting protein structure and function. investigated seven candidate genes associated with T2D pathogenesis from genome‐wide association studies (GWASs) catalog datasets. Subsequently, six mutation‐prediction tools were employed to identify most harmful these genes. Further analysis involved evaluating evolutionary conservation using ConSurf server assessing stability I‐Mutant MUpro. Functional structural effects predicted MutPred2, Project HOPE, FoldAmyloid tools. We obtained 42 deleterious identified Among these, 38 located in highly conserved residues a conservative score 7–9. Furthermore, 20 found decrease stability, 18 them classified as pathogenic mutations. These mutations can either reduce or increase size charge hydrophobic characteristics affected proteins. In addition, eight mutants four amyloidogenic regions, suggesting potential link aggregation. findings provide valuable insights into physicochemical properties changes nsSNPs. concludes distinctive significant suggest for future research. Understanding variants through large‐scale may pave way developing therapeutic interventions targeting variations, ultimately improving our understanding treatment.

Language: Английский

Citations

0