In-silico Analysis for Pathogenicity Prediction of Single Nucleotide Polymorphisms in Human LMO۱ Gene

Background and Aim: : Rhombotin-۱ is a protein that in humans is encoded by the LMO۱ gene. This gene has a length ۴.۴ kb and contains ۵ exons. Its protein comprises two highly conserved, cysteine-rich motifs known as LIM domains, which interact with other proteins. As LMO۱ has no DNA-binding domain, its DNA binding ability is dependent on the other proteins with which it interacts. LMO۱ expression is prominent in the central nervous system in both human and mouse. Genome-wide association studies revealed a correlation between neuroblastoma and single nucleotide polymorphisms in LMO۱ gene, such as rs۱۲۱۳۲۴۸۳۱۰, rs۱۳۹۶۶۸۷۹۷۰, ۵۳۱۰۱۷۹۰۸.Methods: We identified three missense single nucleotide polymorphisms in LMO۱ gene (rs۱۲۱۳۲۴۸۳۱۰: Thr۱۱۶Ile, rs۱۳۹۶۶۸۷۹۷۰: Ala۸۱Asp, rs۱۴۹۰۰۵۷۲۲۹: Met۱Ile), using dbSNP and then analyzed their effect on the protein structure and function using several databases such as SIFT, PolyPhen-۲, and I-Mutant.Results: Our results showed that these missense single nucleotide polymorphisms change the highly conserved amino acids, and have probably damaging effects on protein function (PolyPhen-۲ scores: ۰.۶۹۴, ۰.۹۹۹, and۰.۹۶۵, respectively). The results of the mutation assay in the SIFT database, predict scores more than ۰.۰۵ for all three mentioned SNPs. I-Mutant program, also, presented decrease of protein stability for all of them.Conclusion: : Based on results of the pathogenicity prediction and bioinformatics assessments, we suggest that these nucleotide changes as missense mutations have an important role in the development and/or progression of neuroblastoma.

Keywords:

LMO۱ , Gene , SNP , Structure and function prediction , Neuroblastoma