Journal of Genetics

, 98:104 | Cite as

An in silico approach to characterize nonsynonymous SNPs and regulatory SNPs in human TOX3 gene

  • Mehran Akhtar
  • Tazkira Jamal
  • Jalal ud Din
  • Chandni Hayat
  • Mamoona Rauf
  • Syed Manzoor ul Haq
  • Raham Sher Khan
  • Aftab Ali Shah
  • Muhsin Jamal
  • Fazal JalilEmail author
Research Article


Cancer is one of the deadliest complex diseases having multigene nature where the role of single-nucleotide polymorphism (SNP) has been well explored in multiple genes. TOX high mobility group box family member 3 (TOX3) is one such gene, in which SNPs have been found to be associated with breast cancer. In this study, we have examined the potentially damaging nonsynonymous SNPs (nsSNPs) in TOX3 gene using in silico tools, namely PolyPhen2, SNP&GO, PhD-SNP and PROVEAN, which were further confirmed by I-Mutant, MutPred1.2 and ConSurf for their stability, functional and structural effects. nsSNPs rs368713418 (A266D), rs751141352 (P273S, P273T), rs200878352 (A275T) have been found to be the most deleterious that may have a vital role in breast cancer. Premature stop codon producing SNPs (Q527STOP), rs1259790811 (G495STOP), rs1294465822 (S395STOP) and rs1335372738 (G8STOP) were also found having prime importance in truncated and malfunctional protein formation. We also characterized regulatory SNPs for its potential effect on TOX3 gene regulation and found nine SNPs that may affect the gene regulation. Further, we have also designed 3D models using I-TASSER for the wild type and four mutant TOX3 proteins. Our study concludes that these SNPs can be of prime importance while studying breast cancer and other associated diseases as well. They are required to be studied in model organisms and cell cultures, and may have potential importance in personalized medicines and gene therapy.


breast cancer in silico analysis single-nucleotide polymorphisms protein modelling TOX3 gene. 


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Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  • Mehran Akhtar
    • 1
  • Tazkira Jamal
    • 1
  • Jalal ud Din
    • 1
  • Chandni Hayat
    • 2
  • Mamoona Rauf
    • 3
  • Syed Manzoor ul Haq
    • 1
  • Raham Sher Khan
    • 1
  • Aftab Ali Shah
    • 4
  • Muhsin Jamal
    • 5
  • Fazal Jalil
    • 1
    Email author
  1. 1.Department of BiotechnologyAbdul Wali Khan UniversityMardanPakistan
  2. 2.Department of BiochemistryAbdul Wali Khan UniversityMardanPakistan
  3. 3.Department of BotanyAbdul Wali Khan UniversityMardanPakistan
  4. 4.Departement of BiotechnologyUniversity of MalakandChakdaraPakistan
  5. 5.Department of MicrobiologyAbdul Wali Khan UniversityMardanPakistan

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