• Prediction of potential deleterious nonsynonymous single nucleotide polymorphisms of HIF1A gene: A computational approach
  • Zeinab Jamali,1,* Mortaza Taheri-Anganeh,2 Mona Entezam,3
    1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
    2. Cellular and Molecular Research Center, Research Institute on Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran
    3. Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran


  • Introduction: Hypoxia-inducible factor-1α (HIF-1α) is the oxygen sensitive subunit of HIF1 transcription factor. Its variations is associated with several diseases including different type of cancer, cardiovascular diseases, and liver and kidney failure. Despite all the investigations carried out on the single nucleotide polymorphisms (SNPs) of HIF1A gene and diseases, there are many uncharacterized nonsynonymous SNPs of this gene, which might have damaging effect on the protein function. Therefore, it is worthwhile to analyze these potential damaging nsSNPs, using different bioinformatics tools before launching large population studies. The objective of the present study was to predict the possible deleterious nsSNPs of HIF1A gene and their effects on the function and structure of HIF-1alpha protein, using different bioinformatics tools.
  • Methods: Various prediction servers were used including SIFT, PROVEAN, PolyPhen-2, PANTHER, phD-SNP, SNP-GO, I-Mutant 2.0, Fathmm, SNPeffect 4.0, Mutation taster, CADD and RAMPAGE in a stepwise approach.
  • Results: After analyzing all 454 missense variants of the HIF1A gene using the abovementioned tools, we reported 11 variants with a significant impact on the function or structure of HIF1 α protein. Furthermore, among these variants only S274 P was predicted as stability enhancing variant with effect on protein function by increasing its stability.
  • Conclusion: This is a noticeable point that only S274 P is predicted as stability enhancing variant, which might have an effect on protein function by increasing its stability. Although this is a comprehensive computational study, the need for experimental investigations is still warranted.
  • Keywords: Hypoxiainducible factor1a, Single nucleotide polymorphism, Bioinformatics