In-Silico pathogenicity prediction of rs۸۸۶۰۴۵۸۶۲ and rs۱۴۴۷۸۸۲۵۴ in the LAMB۳ gene in Junctional epidermolysis bullosa (JEB)

Junctional epidermolysis bullosa (JEB) is a major form of epidermolysis bullosa, a group ofgenetic conditions that cause the skin to be very fragile and to blister easily [۱]. LAMB۳ gene mutationsare the most common, causing about ۷۰ percent of all cases of junctional epidermolysis bullosa [۱]. Theproduct encoded by this gene is a laminin that belongs to a family of basement membrane proteins [۲].This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, formslaminin-۵ [۲]. Consequently, this study was undertaken to find the pathogenic SNPs in the LAMB۳gene. Among all SNPs, we studied two SNPs, rs۸۸۶۰۴۵۸۶۲ and rs۱۴۴۷۸۸۲۵۴: rs۸۸۶۰۴۵۸۶۲ affectsprotein function with a score of ۰.۰۲ by the SIFT and is predicted to be possibly damaging with a scoreof ۰.۹۱۸ by the PolyPhen۲. This variant's MetaRNN score is ۰.۲۲۶۷۴۶۳۵ by the Hope and it is morelikely to be pathogenic. Also, thers۱۴۴۷۸۸۲۵۴ affects protein function with a score of ۰.۰۱ by the SIFT,and this mutation is predicted to be probably damaging with a score of ۱.۰۰۰ by the PolyPhen-۲. Hisvariant's MetaRNN score is ۰.۹۷۷۷۰۹۲ by the Hope, and it is more likely to be pathogenic. Theseresidues are located on the surface of the protein; mutation of these residues can disturb interactionswith other molecules or other parts of the protein. In conclusion, this study suggested that G۱۰۰۳S andG۲۸۷S missense variants of the LAMB۳ gene would affect the protein function.

کلیدواژه ها:

Junctional epidermolysis bullosa (JEB) ، LAMB۳ gene ، SNP ، PolyPhen-۲ ، SIFT