EVER gene belongs to larger family of proteins referred to as the transmembrane channel-like protein (TMC) family1. EVER1/TMC6 protein, integral membrane protein, is located in the endoplasmic reticulum (ER) of keratinocytes, where it forms a complex with zinc transporter-1 (ZnT-1) a membrane protein responsible for zinc efflux and resistance to zinc toxicity, thereby controlling the cellular zinc balance2. The EVER1 protein is predicted to have 10 transmembrane domains and 2 leucine zipper motifs1.
The EVER1 gene encodes 2 alternatively spliced proteins, one of 805 amino acids and the other of 454 amino acids, in the same open reading frame. The EVER genes are thought to be transcribed in numerous tissues including the skin1. Mutations in the TMC6 are implicated in the development of the rare autosomal recessive disease Epidermodysplasia Verruciformis (EV)3. EV is characterized by extreme susceptibility to infection by cutaneous human papillomaviruses (HPV) of the beta genus. The TMC6 genes may be involved in controlling HPV gene expression and replication in epidermal keratinocytes or they may directly affect innate and adaptive immune responses which control the clearance of HPV-infected keratinocytes in EV cases4. A recent report indicated an association between genetic variation in the TMC6 region and development of cervical cancer (CxCa) 5.
