Computational Investigation of Non-Synonymous Single Nucleotide Polymorphism in the Human CACNA1C Gene

Introduction: The CACNA1C gene is a voltage-gated calcium channel involved in regulating calcium entry into the cells. The gene is associated with various types of diseases like cancer, schizophrenia, bipolar disease, anxiety, phantom tooth pain, and diabetic peripheral neuropathy. Aim: This study aimed to investigate the missense single nucleotide polymorphism associated with the human CACNA1C gene using bioinformatics tools. Objective: The study focused on understanding the structural and functional distribution of high-risk nsSNPs of the CACNA1C gene using several bioinformatics tools. Methods: Retrieval of missense SNP of CACNA1C gene from NCBI and Uniprot database. Recognition of deleterious nsSNPs using SIFT, Polyphen v2, PROVEAN, Panther, PhD-SNP, and SNPs & GO. Structural stability was detected with the help of I-Mutant and MUPro. GeneMANIA and STRING gave details regarding the gene-gene and protein- protein interactions. Another functional characterization was predicted using SOPMA, AlphaFold, and NetPhos 3.1. Results and Discussion: The functional analysis identified 14 nsSNPs to be deleterious from 1824 non-synonymous missense SNP. The identified nsSNPs, namely, rs34534613, rs79891110, rs80315385, rs199473391, rs199586997, rs200935321, rs368861681, rs369421219, rs370634418, rs376872233, rs377564636, rs200325545, rs267603426, and rs372495864 were subjected to various structural and functional characterization using IMutant 2.0, MUPro, GeneMANIA, STRING, SOPMA, AlphaFold and NetPhos 3.1. Conclusion: Our study recognized 14 nsSNPs to be detrimental to the structure and function of the CACNA1C gene. The identified nsSNPs may aid in serving as a potential therapeutic target for disease diagnosis.