Missense HRC- rs۳۷۴۵۲۹۷ Gene Polymorphisms May Correlate to Humans Cardiac Arrhythmia: A In silico Study

The histidine-rich calcium-binding protein, which is encoded by the HRC gene in humans,plays a crucial role in cardiac arrhythmia development, especially in cases involving calcium-handlingdysfunction [۱]. This sarcoplasmic reticulum (SR) binding protein in the heart muscle cells, acts as anintracellular Ca۲+ buffer and tightly regulates Ca۲+ binding and release [۲]. In silico studies can help toidentify effective single nucleotide polymorphisms (SNPs) in the structure and stability of HRC proteinand to predict their relationship with cardiac arrhythmias [۳]. In this study, missense SNPs of the HRCgene and their effects on arrhythmia were investigated. At first, all missense SNPs of the HRC gene,which is located on chromosome ۱۷q۲۵.۳ monitored. Missense SNPs with a minor allele frequency(MAF)≥ ۰.۱ were selected in the NCBI-dbSNP database. The effect of each of the selected SNPs basedon functional, structural, and stability aspects of the protein were investigated by eleven online software:SIFT, Polyphen-۲, Mutation assessor, PROVEAN, I-mutant, iStable, MUpro, SNPs&GO, PhD-SNP,HOPE, PSIPRED, and GOR-IV. Analysis of missense SNPs performed with SIFT, Polyphen-۲, andMutation assessor software showed that rs۳۷۴۵۲۹۷ (T>G, Ser۹۶Ala), as a transversion mutation, couldbe a deleterious SNP. The prediction of the effects of this transversion by I-mutant, iStable, MUprodatabases, PSIPRED and GOR-IV also showed that the substitution of Serin with Alanine at the residueregion ۹۶ may decrease the stability of the protein and change the secondary structure. Since serine ۹۶of this protein is a critical phosphorylation site for binding to Triadin (TRDN) [۴], which is a regulatoryprotein for releasing Ca۲+, Ser۹۶Ala substitution may prevent this binding and thus disrupt the HRCTRDNpathway in individuals with mutant allele G. Based on this, the rs۳۷۴۵۲۹۷ can be suggested asa molecular marker for further research in cardiac arrhythmia.

کلیدواژه ها:

Cardiac arrhythmia ، HRC gene ، In silico analysis ، Missense SNPs ، Triadin protein