Determination of deleterious single nucleotide polymorphisms of human lactoferrin gene

Abstract

Lactoferrin (LTF) is an important constituent of innate immune system and an antimicrobial peptide (AMP) possessing both antimicrobial and immunomodulatory properties. In this study, missense nonsynonymous single nucleotide polymorphisms (nsSNPs) of LTF gene were systematically collected and analyzed for their deleterious nature using various computational methods. Different in silico tools were used to analyze nsSNPs of LTF gene. The nsSNPs were first subjected to SIFT and Polyphen v2 tools. These nsSNPs were further analyzed by other online tools – PROVEAN, SNAP, PhD-SNP and SNPs&GO to increase the likelihood of effective prediction. I-Mutant 3.0 was employed to predict the consequence of variants on LTF protein’s stability. Gene and protein interactions of LTF protein were studied by GeneMANIA and STRING tools respectively. FT site server was used to infer the ligand binding sites of LTF protein. Also, the nsSNPs of LTF gene were subjected to PROJECT HOPE analysis. SIFT and Polyphen v2 tools observed 32 SNPs to be deleterious and probably damaging respectively. Gene and protein interaction networks predicted that LTF protein interacted with lysozyme and neutrophil gelatinase associated lipocalin (LCN2). PROJECT HOPE analysis predicted that G422C, G130C, P614L, P614S, T666I, E34K, C424R, G493D, L430Q, C250R, R360W, G528D and W366C were damaging to LTF protein. LTF gene nsSNPs were predicted for their deleterious nature by using various in silico tools which could form the baseline for further analyzing them using experimental work and could be potentially used for precision medicine.