Screening for Deleterious non-synonymous SNPs in Human CCL21 Gene using in-silico analysis

Authors

  • Yasir Ali Department of Biotechnology, Abdul Wali Khan University Mardan, KPK, Pakistan
  • Mehran Akhtar Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan
  • Kainat Khan Department of Biotechnology, Abdul Wali Khan University Mardan, KPK, Pakistan
  • Nadia Farooqi Department of Biotechnology, Abdul Wali Khan University Mardan, KPK, Pakistan
  • Shahla Gohar Department of Biotechnology, Abdul Wali Khan University Mardan, KPK, Pakistan
  • Syed Ishfaq Ahmad Department of Biotechnology and Genetic Engineering, Hazara University Mansehra Pakistan
  • Madeeha Ayaz Department of Biotechnology, Abdul Wali Khan University Mardan, KPK, Pakistan
  • Zia Ul Islam Department of Biotechnology, Abdul Wali Khan University Mardan, KPK, Pakistan
  • Maria Arshad Department of Research & Innovation, Shalamar Institute of Health Sciences, Lahore, Pakistan
  • Fazal Jalil Department of Biotechnology, Abdul Wali Khan University Mardan, KPK, Pakistan

DOI:

https://doi.org/10.53992/njns.v6i2.79

Keywords:

CCl21, nsSNPs, Polymorphisms, Gene-gene interactions, In silico

Abstract

Rheumatoid arthritis (RA) is a chronic, systematic, and progressive inflammatory disorder, causing severe damage to joints and hence increase mortality. The Chemokine (C-C motif) ligand 21 (CCL21), a member cytokines family, is involved in immuno-inflammatory and regulatory processes. Therefore, identifying the important SNPs (single nucleotide polymorphisms) in the CCL21 gene is of key importance to evaluate their structural and functional significance and to discover novel therapeutic targets for immune-related diseases, including RA. In this study, we used in silico approaches for identifying the most damaging non-synonymous SNPs (nsSNPs), playing a significant structural and functional role in CCL21 protein. The primary tools used for this study included PROVEAN, SNPs&GO, SIFT and PolyPhen2. Other tools, its stability, Structure and functional effect as well as the conservation profile, were verified using I-Mutant, MutPred, and ConSurf. The site of post-translational modification also predicted. The 3-D modeling of proteins was carried out using I-TASSER which were then visualized in Chimera v1.11. Furthermore, the gene-gene interactions were predicted using STRING and gene MANIA. It was observed that the nsSNPs D30Y (rs753133670), I62N (rs1170851787), R75C (rs759733358), R75S (rs776954599) and A83V (rs776954599) were the most damaging nsSNPs in the CCL21 gene. These nsSNPs might have a significant role in CCL2 protein’s malfunctioning and possibly causing different autoimmune diseases including RA. Our study concluded that, to study the correlation of the CCL21 gene with certain autoimmune disorders, i.e. Crohn’s Disease (CD), RA and other immune-associated diseases, these SNPs could be the most important ones. In addition, these SNPs need to be studied in animal models and cell cultures in association with certain diseases, to identify if they could be of use for the gene therapy and pharmacogenomics.

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Published

2022-02-28

How to Cite

Ali, Y., Akhtar, M., Khan, K., Farooqi, N., Gohar, S., Ishfaq Ahmad, S., … Jalil, F. (2022). Screening for Deleterious non-synonymous SNPs in Human CCL21 Gene using in-silico analysis. NUST Journal of Natural Sciences, 6(2). https://doi.org/10.53992/njns.v6i2.79