Background and Aim:  CD151, a tetraspanin component of the hemidesmosome, is essential for skin integrity, and its dysfunction can cause Epidermolysis Bullosa Simplex (EBS).  This study aimed to predict high-risk SNPs in the CD151 gene and evaluate their impact on the protein's stability, structure, and function using bioinformatics.
Materials and Methods: CD151 SNPs were collected from dbSNP, and the protein sequence from UniProt. Comprehensive bioinformatics tools were used for effect prediction. Mutation risk and disease association were assessed using SIFT, PROVEAN, PolyPhen-2, PANTHER, and meta-predictors like Meta-SNP. Stability changes were predicted by I-Mutant and MUpro, and sequence conservation by ConSurf. Secondary/tertiary structures were modeled using NetSurfP-2.0, SOPMA, and HOPE, with protein-protein interactions analyzed by STRING and GeneMANIA.
Results: Screening 27 polymorphisms identified 8 high-risk variants: A81T, R87L, D147N, A145D, F153C, R178C, G227S, and G229S. Predictions showed these SNPs cause a reduction in protein stability, are predominantly located in conserved regions, and disrupt alpha-helical structures, thereby disturbing the overall protein fold. Altered surface positioning of mutated residues could also impair critical CD151 interactions.
Conclusion: The computational analyses and screenings demonstrated that 8 key CD151 mutations potentially destabilize the protein and structure, altering its secondary structure and interactions. These SNPs have significant reference value for future studies. The identification of these high-risk SNPs paves the way for the design of targeted molecular screening panels for EBS patients, which could aid in earlier and more precise diagnosis. Final confirmation of these results necessitates further clinical and laboratory studies.