In Silico Analysis on the Structural and Functional Impact of One Deleterious Snp in Nkx2.5 Gene Associated With Congenital Heart Disease (Chd)

Background and aim: the heart is the first organ that formed in the vertebrate embryo. its function is to collect blood from the body and send it to the lungs and receive blood from the lungs and send it to the rest organs of the body. congenital heart disease (chd), a type of cardiovascular disease, is the most common birth defect and refers to a defect in heart structure or function from birth. the most common chd is a ventricle septal defect (vsd). various environmental and genetic factors are involved in this disease. about 1,700 genes involved in cardiac development have been reported. genes with mutations in congenital heart disease include nkx2.5, gata4, and tbx5, all of which interact with each other. nkx2.5 transcription factor, located in 5q35.1, is crucial in guiding the mesoderm to become heart tissue and activates the synthesis of other transcription factors such as members of the gata4 and mef2 family. this gene is a member of the homeobox nk gene family that has been conserved throughout evolution. mutations in this gene have been reported in different types of chds. nkx2.5 protein acts as a key regulator in cardiac morphogenesis. nkx2.5 gene has 1822 snps until now which among them 44 snps are pathogenic. rs72554028 of the nkx2.5 gene is located in 3' utr region and is a missense mutation.methods: in this study, we analyzed pathogenicity effects of this snp in nkx2.5 gene by sift (sorting intolerant from tolerant, is a tool for prediction of snp effect on protein function), polyphen2 (is a tool for annotating coding non-synonymous snps), i-mutant2.0 (is a tool for prediction of protein stability changes upon single point mutation) and swiss-model (is a tool for examining the 3d structure of proteins) prediction databases.results: . sift database predicted that rs104894073 effects on the protein function. polyphen2 database is predicted this snp probably damaging. i-mutant2.0 database is predicted this snp decrease stability and swiss-model is predicted that the three-dimensional structure of the mutant protein was significantly different from the normal protein. conclusion: . in conclusion rs72554028 of nkx2.5 gene reduces protein stability and probably associated with disease in humans.