In Silico Characterization of Genetic Alterations Associated with Mal De Meleda

Abstract

Mal de Meleda (MDM) is an autosomal recessive skin disorder majorly caused by mutations in the ARS gene encoding SLURP-1 protein secreted by Keratinocytes. A number of genetic alterations have already been reported in SLURP1 associated with MDM, theoretically proposed to affect the integrity of the downstream product. There are a no reports available to the best of our knowledge, which characterize the effect of respective mutations at the protein structural level, which is the focus of this study. The protein sequence of SLURP1 was obtained from the UniProt database and the disease associated alterations were retrieved and mined from the literature resources. Domain analysis showed that the protein belongs to the Ly6/uPAR superfamily, has antitumor activity and is also a marker of late skin differentiation. Complete tertiary structure of SLURP1 was predicted as shown in figure 4, for further structural analysis as was not previously determined and was submitted to the PMDB after systematic evaluation and validation (PMDB ID: PM0077826). Structural abnormalities in the protein due to mutations were explored through comparative structural analysis along with interspecies conservation of the respective residue through phylogenetic analysis. It is expected that this systematic structural analysis will enhance our understanding about the disease mechanism and will also help to develop better diagnosis and designing treatment strategies in the near future against MDM and other relevant disorders.