title: A comprehensive in silico analysis of the functional and structural impact of SNPs in the IGF1R gene.
abstract: Insulin-like growth factor 1 receptor (IGF1R) acts as a critical mediator of cell proliferation and survival. Many single nucleotide polymorphisms (SNPs) found in the IGF1R gene have been associated with various diseases, including both breast and prostate cancer. The genetics of these diseases could be better understood by knowing the functions of these SNPs. In this study, we performed a comprehensive analysis of the functional and structural impact of all known SNPs in this gene using publicly available computational prediction tools. Out of a total of 2412 SNPs in IGF1R retrieved from dbSNP, we found 32 nsSNPs, 58 sSNPs, 83 mRNA 3' UTR SNPs, and 2225 intronic SNPs. Among the nsSNPs, a total of six missense nsSNPs were found to be damaging by both a sequence homology-based tool (SIFT) and a structural homology-based method (PolyPhen), and one nonsense nsSNP was found. Further, we modeled mutant proteins and compared the total energy values with the native IGF1R protein, and showed that a mutation from arginine to cysteine at position 1216 (rs61740868) on the surface of the protein caused the greatest impact on stability. Also, the FASTSNP tool suggested that 31 sSNPs and 3 intronic SNPs might affect splicing regulation. Based on our investigation, we report potential candidate SNPs for future studies on IGF1R mutations.
authors.affiliation: Departamento de Bioquímica e Imunologia, Bioinformática, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte, MG, Brazil. sergiodealencar@gmail.com
authors.forename: S A
authors.initials: SA
authors.lastname: de Alencar
authors.forename: Julio C D
authors.initials: JC
authors.lastname: Lopes
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D006801:Humans; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017433:Protein Structure, Secondary; D017526:Receptor, IGF Type 1 / Q000737:chemistry* / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013816:Thermodynamics
chemical_list: D050505:Mutant Proteins; D017526:Receptor, IGF Type 1