Cataract-related mutations in EphA2: a survey of literature data and the relevance of the receptor Sam domain

Introduction: EphA2 is a receptor tyrosine kinase that is associated with various pathological conditions. Mutations in EphA2 are linked to cataract, an eye disorder manifesting as lens opacity, and representing one of the most prominent causes of blindness worldwide. Areas covered: We collected a list of cataract-related EphA2 mutations and positioned them inside the different protein domains to identify regions of the receptor that could be more likely considered targets in the ‘anti-cataract’ drug discovery field. Moreover, we analyzed the structural consequences these mutations could induce. A search for literature related to EphA2 and cataracts was carried out through the PubMed National Library of Medicine. Structural information on diverse EphA2 domains was obtained from the Protein Data Bank. EphA2 variants connected to cataract were checked on the databases Cat-Map and dbSNP. Expert opinion: Cataract-related mutations are gathered within diverse EphA2 domains and are abundant inside its Sam (Sterile alpha motif, EphA2-Sam) domain. Mutations affecting EphA2-Sam could disturb domain helical fold and hamper interaction with other Sam domains, eventually interfering with EphA2 cell migration activity. Identification of stabilizing small molecules targeting EphA2-Sam pathogenic variants could represent an original route to discover novel therapeutic compounds against lens opacity.