Bioinformatics Analysis of Non-Synonymous Single Nucleotide Polymorphisms in Human Adk Gene

IF 0.6 4区生物学 Q4 GENETICS & HEREDITY Russian Journal of Genetics Pub Date : 2024-06-19 DOI:10.1134/s1022795424700273

P. Farrokh

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Abstract

Adenosine kinase (ADK) controls adenosine levels. Abnormal concentration of adenosine lead to multiple disorders in humans. In this study, the effect of non-synonymous single nucleotide polymorphisms (nsSNPs) in human Adk was evaluated on the structure and function of long and short ADK isoforms (ADK-L and ADK-S) using computational tools. Of the 244 coding nsSNPs retrived in Adk, 66 amino acid changes were deleterious by at least five tools: SIFT, PhD-SNP, SNPs&GO, SuSPect, SNAP2, FATHMM, and PolyPhen-2. I-Mutant 2.0 and MUpro showed that among them, 26 substitutions had a strong destabilizing effect on both ADK isoforms. The conserved region and secondary structure of ADK isoforms were predicted by the ConSurf and NetSurfP-3.0 servers, respectively. The HOPE server displayed that 11 nsSNPs, due to the change in amino acid properties, had adverse effects on ADK isoforms. Docking analysis showed that L151 and F218 in ADK-L and their corresponding residues in ADK-S are located in the ligand-binding site and their mutations changed the cavity structure or ligand binding affinity. In conclusion, this study, by using computational methods, identified 11 harmful nsSNPs in human Adk. These predictive results facilitate the association of these nsSNPs with disease susceptibility in population studies.

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人类 Adk 基因非同义单核苷酸多态性的生物信息学分析

摘要腺苷激酶（ADK）控制着腺苷水平。腺苷浓度异常会导致人类多种疾病。本研究利用计算工具评估了人类腺苷酸激酶中的非同义单核苷酸多态性（nsSNPs）对长短腺苷酸激酶同工酶（ADK-L 和 ADK-S）的结构和功能的影响。在 Adk 中检索到的 244 个编码 nsSNPs 中，至少有五种工具发现 66 个氨基酸的变化是有害的：SIFT、PHD-SNP、SNPs&GO、SuSPect、SNAP2、FATHMM 和 PolyPhen-2。I-Mutant 2.0 和 MUpro 显示，其中 26 个取代对 ADK 两种异构体都有强烈的不稳定作用。ConSurf 和 NetSurfP-3.0 服务器分别预测了 ADK 异构体的保守区和二级结构。HOPE 服务器显示，有 11 个 nsSNPs 由于氨基酸性质的改变而对 ADK 同工酶产生了不利影响。对接分析表明，ADK-L 中的 L151 和 F218 以及 ADK-S 中的相应残基位于配体结合位点，它们的突变改变了空腔结构或配体结合亲和力。总之，本研究利用计算方法在人类 Adk 中发现了 11 个有害的 nsSNPs。这些预测结果有助于在人群研究中将这些 nsSNPs 与疾病易感性联系起来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Russian Journal of Genetics 生物-遗传学

CiteScore

1.00

自引率

33.30%

发文量

126

审稿时长

1 months

期刊介绍： Russian Journal of Genetics is a journal intended to make significant contribution to the development of genetics. The journal publishes reviews and experimental papers in the areas of theoretical and applied genetics. It presents fundamental research on genetic processes at molecular, cell, organism, and population levels, including problems of the conservation and rational management of genetic resources and the functional genomics, evolutionary genomics and medical genetics.