• Predicting the Pathogenicity of a Missense Single Nucleotide Polymorphism (rs121913240) in the KRAS Gene Associated with Lung Cancer
  • Mahsa Mirzaei,1,* Mohammad Mehdi Heidari,2 Mehri Khatami,3
    1. Department of Biology, Yazd University, Yazd, Iran.
    2. Department of Biology, Yazd University, Yazd, Iran.
    3. Department of Biology, Yazd University, Yazd, Iran.


  • Introduction: Lung cancer (LC) is caused by the uncontrollable division of lung tissue cells. This cancer is the leading cause of cancer-related death worldwide. Early diagnosis can reduce the number of deaths from LC. Identification of genetic mutations is important for the diagnosis and targeted treatment of lung cancer. Nucleotide changes in many different genes like Kirsten rat sarcoma viral oncogene homologue (KRAS) gene have been found in LC. KRAS is located on chromosome 12 and is a member of the RAS family of genes associated with human cancers. KRAS encodes a GTPase that plays a key role in signal transduction cascades and thus, is critical for cell proliferation, survival, and differentiation. The purpose of this study is to investigate the pathogenicity effect of a missense single nucleotide polymorphism (rs121913240) in the KRAS gene using bioinformatics tools.
  • Methods: In this study, among the identified polymorphisms in the National Center for Biotechnology Information/Single Nucleotide Polymorphism database (NCBI/dbSNP), rs121913240 was selected. In the rs121913240 variant, the amino acid glutamine is replaced by leucine in position 61 (p.Gln61Leu). We investigated the pathogenicity of this missense variant, the secondary structure of its wild-type and mutated proteins, and the possible effect of amino acid substitution on protein structure and function. For this purpose, we used several bioinformatics servers including PolyPhen-2, SIFT, PSIPRED, I-Mutant, mCSM-stability, SNPs&GO, PredictSNP and HOPE.
  • Results: PolyPhen-2 server indicated that the variant with dbSNP ID rs121913240 (Q61L) is probably damaging with a score of 0.977. The score of 0.00 by the SIFT server showed that this variant has a significant effect on the structure and function of the protein. The secondary structures of wild-type and mutated proteins were compared by the PSIPRED server. According to the PSIPRED result, unlike the amino acid leucine, glutamine was placed in the alpha-helix region of the protein. Also, protein stability increased according to the DDG value in I-Mutant and mCSM-stability servers. Moreover, this variant was predicted as deleterious and disease using PredictSNP and SNPs&GO servers. In addition, the HOPE results indicated that the mutated residue is located in a domain that is important for the binding of other molecules and it might affect the function of the protein.
  • Conclusion: In this study, the rs121913240 variant in the KRAS gene has been identified from the NCBI/dbSNP. According to the results, the pathogenicity of this variant was confirmed using powerful bioinformatics tools. These results can be examined with experimental studies. Analysis of the SNPs is important for the early diagnosis and targeted treatment of cancer.
  • Keywords: Single nucleotide polymorphism, rs121913240, KRAS gene, Lung cancer