Disease-associated single nucleotide polymorphisms (SNPs) alter the natural functioning and the structure of proteins. Glutamic-oxaloacetic transaminase 1 (GOT1) is a gene associated with multiple cancers and neurodegenerative diseases which codes for aspartate aminotransferase. The present study involved a comprehensive in-silico analysis of the disease-associated SNPs of human GOT1. Four highly deleterious nsSNPs (L36R, Y159C, W162C and L345P) were identified through SNP screening using several sequence-based and structure-based tools. Conservation analysis and oncogenic analysis showed that most of the nsSNPs are at highly conserved residues, oncogenic in nature and cancer drivers. Molecular dynamics simulations (MDS) analysis was performed to understand the dynamic behaviour of native and mutant proteins. PTM analysis revealed that the nsSNP Y159C is at a PTM site and will mostly affect phosphorylation at that site. Based on the overall analyses carried out in this study, L36R is the most deleterious mutation amongst the aforementioned deleterious mutations of GOT1.

疾病相关的单核苷酸多态性 (SNP) 改变了蛋白质的自然功能和结构。谷氨酸-草酰乙酸转氨酶 1 (GOT1) 是一种与多种癌症和神经退行性疾病相关的基因，它编码天冬氨酸氨基转移酶。本研究涉及对人类 GOT1 的疾病相关 SNP 进行全面的计算机分析。使用几种基于序列和基于结构的工具通过 SNP 筛选鉴定了四种高度有害的 nsSNP（L36R、Y159C、W162C 和 L345P）。保守性分析和致癌性分析表明，大多数 nsSNPs 是高度保守的残基，具有致癌性和癌症驱动力。进行分子动力学模拟 (MDS) 分析以了解天然和突变蛋白质的动态行为。PTM 分析显示 nsSNP Y159C 位于 PTM 位点，主要影响该位点的磷酸化。根据本研究中进行的总体分析，L36R 是上述 GOT1 有害突变中最有害的突变。