Screening and insilico analysis of deleterious nsSNPs (missense) in human CSF3 for their effects on protein structure, stability and function. (October 2019)

• Record Type: Journal Article
• Authors: Guttula, Praveen Kumar; Chandrasekaran, Gopalakrishnan; Gupta, Mukesh Kumar
• Is Part Of: Computational biology and chemistry. Volume 82(2019)
• Page Start: 57
• Page End: 64
• Publication Date: 2019-10
• Subjects: SNP single nucleotide polymorphism -- CSF3 colony stimulating factor 3 -- G-CSF granulocyte colony stimulating factor -- CSF3R colony stimulating factor 3 Receptor -- nsSNP non-synonymous SNP -- SIFT sorting intolerant from tolerant -- PolyPhen polymorphism and phenotyping -- UTR untranslated region -- PDB Protein Data Bank -- dbSNP SNP Database (NCBI) -- RMSD root mean square deviation -- BLASTp protein basic local alignment search tool; CSF3 -- Neutropenia -- SNP -- PROVEAN -- PolyPhen -- SIFT; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2019.06.001
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: 18.9% of all the SNPs in the dbSNP database for CSF3 gene were present in the coding region. 20 nsSNPs were identified as deleterious and important for the protein stability of CSF3. 20 nsSNPs may be used for the wider population-based genetic studies and also should be taken into account while engineering the recombinant CSF3 protein for clinical use. Abstract: Human granulocyte colony stimulating factor (hG-CSF), known as CSF3, plays an important role in the growth, differentiation, proliferation, survival, and activation of the granulocyte cell lineage such as neutrophils and their precursors. Functional reduction in native CSF3 protein results in reduced proliferation and activation of neutrophils and leads to neutropenia. Single nucleotide polymorphisms (SNPs) in the CSF3 gene may have deleterious effects on the CSF3 protein function. This study was undertaken to find the functional SNPs in the human CSF3 gene. Results suggest that 18.9% of all the SNPs in the dbSNP database for CSF3 gene were present in the coding region. Out of 59 non-synonymous SNPs (nsSNPs), 26 nsSNPs were predicted to be non-tolerable by SIFT whereas 18 and 7 nsSNPs were predicted as probably damaging and possibly damaging, respectively by PolyPhen. Among this 31 nsSNPs, 16 nsSNPs were identified to be potentially deleterious by PANTHER server, and 4 nsSNPs were found to be neutral by PROVEAN. SNPAnalyzer predicted 7 nsSNPs to be neutral phenotype and the remaining 24 nsSNPs to be associated with diseases. Among the predicted nsSNPs, rs144408123, rs144408123, rs145136406, rs145311241, rs373191696, rs762945096, rs763688260, rs767572172, rs775326370, rs777777864, rs777983866, rs781596455, rs139072004, rs757612684, rs772911210, rs139072004, rs746634544, rs749993200, rs763426127, rs772466210 were identified as deleterious and potentially damaging. I-Mutant analysis revealed that th 20 nsSNPs were important for protein stability of CSF3. Therefore, th 20 nsSNPs may be used for the wider population-based genetic studies and also should be taken into account while engineering the recombinant CSF3 protein for clinical use.