title: Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis.
abstract: Mutations of TMC1 cause deafness in humans and mice. TMC1 and a related gene, TMC2, are the founding members of a novel gene family. Here we describe six additional TMC paralogs (TMC3 to TMC8) in humans and mice, as well as homologs in other species. cDNAs spanning the full length of the predicted open reading frames of the mammalian genes were cloned and sequenced. All are strongly predicted to encode proteins with 6 to 10 transmembrane domains and a novel conserved 120-amino-acid sequence that we termed the TMC domain. TMC1, TMC2, and TMC3 comprise a distinct subfamily expressed at low levels, whereas TMC4 to TMC8 are expressed at higher levels in multiple tissues. TMC6 and TMC8 are identical to the EVER1 and EVER2 genes implicated in epidermodysplasia verruciformis, a recessive disorder comprising susceptibility to cutaneous human papilloma virus infections and associated nonmelanoma skin cancers, providing additional genetic and tissue systems in which to study the TMC gene family.
authors.affiliation: Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 20850, Rockville, MD, USA
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kurima
authors.forename: Yandan
authors.initials: Y
authors.lastname: Yang
authors.forename: Katherine
authors.initials: K
authors.lastname: Sorber
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D004819:Epidermodysplasia Verruciformis / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D034381:Hearing Loss / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D008565:Membrane Proteins; C451751:TMC1 protein, human; C470314:TMC6 protein, human; C470315:TMC8 protein, human