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Abstract：
The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS.
摘要：
TBX1基因在22q11.2缺失综合征（22q11.2DS）的发展中起关键作用，与各种表型表现相关的复杂遗传疾病。在这项研究中,我们进行了计算机分析，以鉴定TBX1基因中潜在有害的非同义单核苷酸多态性（nsSNP），并评估其对22q11.2DS的功能和结构影响。采用涉及多种计算工具的综合分析管道来预测nsSNP的致病性。这项研究评估了蛋白质的稳定性，并探索了蛋白质-蛋白质相互作用的潜在变化。结果显示rs751339103(C>A)，rs780800634（G>A），rs1936727304(T>C),rs1223320618（G>A），rs1248532217（T>C），rs1294927055(C>T),rs1331240435(A>G,rs1601289406(A>C),rs1936726164(G>A),和rs911796187（G>A）具有影响蛋白质功能和稳定性的高风险潜力。进一步分析了这些nsSNP对翻译后修饰和结构特征的影响，表明它们可能破坏与TBX1及其相互作用伙伴相关的分子途径。这些发现为进一步的实验研究和阐明受22q11.2DS影响的个体的潜在治疗靶标和个性化治疗方法奠定了基础。
