The EVER gene belongs to a larger family of proteins referred to as the transmembrane channel-like protein (TMC) family¹. The EVER1/TMC6 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, and 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 805 amino acids long and the other 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.