International Journal of Molecular and Cellular Medicine (IJMCM)

Mendeley  

Zotero  

Sadaf T, John P, Bhatti A. Comprehensive Computational Analysis of Protein Phenotype Changes Due to Plausible Deleterious Variants of Human SPTLC1 Gene. Int J Mol Cell Med 2019; 8 (1) :67-83
URL: http://ijmcmed.org/article-1-948-fa.html

Genetic variations found in the coding and non-coding regions of a gene are known to influence the structure as well as the function of proteins. Serine palmitoyltransferase long chain subunit 1 a member of α-oxoamine synthase family is encoded by SPTLC1 gene which is a subunit of enzyme serine palmitoyltransferase (SPT). Mutations in SPTLC1 have been associated with hereditary sensory and autonomic neuropathy type I (HSAN-I). The exact mechanism through which these mutations elicit protein phenotype changes in terms of structure, stability, and interaction with other molecules is unknown. Thus, we aimed to perform a comprehensive computational analysis of single nucleotide polymorphisms (SNPs) of SPTLC1 to prioritize a list of potential deleterious SNPs and to investigate the protein phenotype change due to functional polymorphisms. In this study, a diverse set of SPTLC1 SNPs were collected and scrutinized to categorize the potential deleterious variants. Our study concordantly identified 21 non-synonymous SNPs as pathogenic and deleterious that might induce alterations in protein structure, flexibility and stability. Moreover, evaluation of frameshift, 3’ and 5’ UTR variants shows c.*1302T>G as effective. This comprehensive in silico analysis of systematically characterized list of potential deleterious variants could open avenues as primary filter to substantiate plausible pathogenic structural and functional impact of variants.