GSDME (Gasdermin E)/DFNA5/ICERE-1 [G9]

GSDME (Gasdermin E), known as DFNA5 (deafness, autosomal dominant 5) or ICERE-1, is a 496 amino acid protein encoded by this gene located at 7p15.3. It is expressed in cochlea tissue, placenta, brain, heart, liver, lung and pancreas as two alternatively spliced isoforms, designated short and long. Defects in this gene are the cause of nonsyndromic sensorineural deafness autosomal dominant type 5 (DFNA5), a form of sensorineural hearing loss that results from damage to one of various structures that receive sound information in the brain. Defects in some of the genes localized to chromosome 7 have been linked to Osteogenesis imperfecta, Williams-Beuren syndrome, Pendred syndrome, Lissencephaly, Citrullinemia and Shwachman-Diamond syndrome. Some studies found that GSDME is epigenetically inactivated in gastric, colorectal and breast cancer which is in line with its apoptosis-inducing properties. If apoptosis is an intrinsic feature of GSDME, shutting the gene down in tumor cells makes them more susceptible to uncontrolled cellular growth. Moreover, the fact that GSDME is regulated by P53 strongly suggests that GSDME is a tumor suppressor gene.