Class III malocclusion is a special type of jaw deformity that can result mandibular prognathism (MP) [1]. Genetic factors such as single nucleotide polymorphisms (SNPs) can cause this protrusion. Nidogen-1 is an extracellular glycoprotein encoded by the NID1 gene and plays a crucial role in stabilizing, cell adhesion, and mediating cell-matrix interactions. In silico studies can help to identify effective SNPs in the structure and stability of Nidogen-1 and to predict their relationship with MP. In this study, missense SNPs of the NID1 gene and their effects on MP were investigated. At first, all missense SNPs of the NID1 gene monitored. Missense SNPs with a minor allele frequency (MAF)≥ 0.1 were selected in the NCBI-dbSNP database. The effect of each selected SNPs based on functional, structural, and stability aspects of the protein and mRNA were investigated by twelve online software:SIFT, Polyphen-2, Meta LR, PantherDB, PROVEAN, I-mutant, iStable, MUpro, FATHMM, RNAsnp, PSIPRED, and GeneMANIA. Analysis of missense SNPs by SIFT, Polyphen-2, and PantherDB showed that rs3738531 (C>A, Gln807His), could be as a deleterious SNP. The prediction of the effects of this SNP by I-mutant, iStable, MUpro, and PSIPRED also showed substitution of Gln807His may decrease the stability of the protein. Analysis association of NID1 by GeneMANIA showed that this protein has a co-expression and Physical Interactions with the heparan sulfate proteoglycan 2 (HSPG2), which is known as Perlecan, with a score of 0.013352894 [2]. Perlecan and Nidogen-1 impact chondrocyte and osteoblast functions [3]. Given their roles, the co-expression of HSPG2 and NID1 may have implications for MP. Furthermore, rs3738531 has been associated with structural changes in mRNA with a significant P-value, potentially emphasizing the translation of NID1. Based on this study, the NID1 gene plays an important role in MP development and rs3738531 is expected to be effective in mandibular growth.
