Prediction of Damage‐Associated Non‐Synonymous Single Nucleotide Polymorphisms in the Human LAMB2 Gene: A Computational Study

Abstract

Laminins are a major component of basement membranes, and they consist of a unique combination of three non‐identical sub‐chains, giving rise to at least 15 laminin isoforms. The laminin subunit β2 (LAMB2) gene encodes laminin β2, a sub‐chain of several laminins. LAMB2 has been identified as a risk locus for Pierson syndrome, nephrotic syndrome type 5 as well as chronic kidney disease of unknown etiology (CKDu). We conducted this study to predict damage‐associated non‐synonymous single nucleotide polymorphisms (nsSNPs) in LAMB2. nsSNPs were analyzed using 22 in silico prediction tools based on evolutionary, structural and consensus approaches. All tools showed a significant correlation with each other (p < 0.05) and a significant association between their categorical predictions (p < 0.05). Out of the 853 nsSNPs located in LAMB2, 221 nsSNPs within the functional domains were identified as damaging by ≥10 individual tools and by at least two consensus tools. These nsSNPs were distributed among EGF‐like (136), Laminin IV type B (25) and laminin N‐terminal domains (60). The effects of the damage‐associated nsSNPs located in these domains were found to be more deleterious than those found in other regions (Kruskal‐Wallis test H: 99.570, p = 0.001, df = 3). Overlaps between the identified damage‐associated nsSNPs and post‐translational modification sites were also identified. Future work will include modeling of the predicted damage‐associated nsSNPs, identification of the potential consequences to LAMB2 structure, and its disease association. The predicted damage‐associated nsSNPs will provide insight into the possible causes of LAMB2‐associated diseases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.