Gene Symbol: TMC6
Description: transmembrane channel like 6
Alias: EV1, EVER1, EVIN1, LAK-4P, transmembrane channel-like protein 6, epidermodysplasia verruciformis 1, epidermodysplasia verruciformis protein 1, expressed in activated T/LAK lymphocytes, protein LAK-4
Species: human
Products:     TMC6

Top Publications

  1. Tate G, Suzuki T, Kishimoto K, Mitsuya T. Novel mutations of EVER1/TMC6 gene in a Japanese patient with epidermodysplasia verruciformis. J Hum Genet. 2004;49:223-5 pubmed
    Germline mutations of the EVER1/TMC6 gene are associated with epidermodysplasia verruciformis (EV), which is characterized by an abnormal susceptibility to human papillomaviruses that were considered to be innocuous for the general ..
  2. Ramoz N, Taieb A, Rueda L, Montoya L, Bouadjar B, Favre M, et al. Evidence for a nonallelic heterogeneity of epidermodysplasia verruciformis with two susceptibility loci mapped to chromosome regions 2p21-p24 and 17q25. J Invest Dermatol. 2000;114:1148-53 pubmed
    ..We recently mapped a susceptibility locus for epidermodysplasia verruciformis (EV1) to chromosome 17qter within the 1 cM interval between markers D17S939 and D17S802...
  3. Keresztes G, Mutai H, Heller S. TMC and EVER genes belong to a larger novel family, the TMC gene family encoding transmembrane proteins. BMC Genomics. 2003;4:24 pubmed publisher
    ..Mutations in two homologous genes, EVER1 and EVER2 increase the susceptibility to infection with certain human papillomaviruses resulting in high risk of ..
  4. Castro F, Ivansson E, Schmitt M, Juko Pecirep I, Kjellberg L, Hildesheim A, et al. Contribution of TMC6 and TMC8 (EVER1 and EVER2) variants to cervical cancer susceptibility. Int J Cancer. 2012;130:349-55 pubmed publisher
    ..candidate gene follow-up based on: (i) strong clinical evidence demonstrating that mutations in the TMC6 and TMC8 (EVER1 and EVER2) genes associate with the HPV-associated disease epidermodysplasia verruciformis (EV) and (ii) recent ..
  5. Lazarczyk M, Pons C, Mendoza J, Cassonnet P, Jacob Y, Favre M. Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses. J Exp Med. 2008;205:35-42 pubmed
    ..Invalidating mutations in either of two genes (EVER1 and EVER2) with unknown functions cause most EV cases...
  6. Ramoz N, Rueda L, Bouadjar B, Montoya L, Orth G, Favre M. Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet. 2002;32:579-81 pubmed
    ..Here we report the identification of nonsense mutations in two adjacent novel genes, EVER1 and EVER2, that are associated with the disease...
  7. Ramoz N, Rueda L, Bouadjar B, Favre M, Orth G. A susceptibility locus for epidermodysplasia verruciformis, an abnormal predisposition to infection with the oncogenic human papillomavirus type 5, maps to chromosome 17qter in a region containing a psoriasis locus. J Invest Dermatol. 1999;112:259-63 pubmed
    ..The EV locus (named EV1) is included in the 17qter region recently found to contain a dominant locus for the susceptibility to familial ..
  8. Lazarczyk M, Dalard C, Hayder M, Dupré L, Pignolet B, Majewski S, et al. EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation. PLoS ONE. 2012;7:e39995 pubmed publisher
    ..Key elements of this barrier are the EVER1 and EVER2 proteins, as deficiency in either one of the EVER proteins leads to Epidermodysplasia Verruciformis (EV),..
  9. Boulton K, Nolan M, Wu Z, Psifidi A, Riggio V, Harman K, et al. Phenotypic and genetic variation in the response of chickens to Eimeria tenella induced coccidiosis. Genet Sel Evol. 2018;50:63 pubmed publisher
    ..Trait weightings of the first eigenvector, (EV1, eigenvalue = 59%), were biologically interpreted as representing a response of birds that were susceptible to ..

More Information


  1. Leiding J, Holland S. Warts and all: human papillomavirus in primary immunodeficiencies. J Allergy Clin Immunol. 2012;130:1030-48 pubmed publisher
    ..It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and dedicator of cytokinesis 8 (DOCK8) are typically associated with extensive HPV ..
  2. Kalińska Bienias A, Kostrzewa G, Malejczyk M, Ploski R, Majewski S. Possible association between actinic keratosis and the rs7208422 (c.917A→T, p.N306l) polymorphism of the EVER2 gene in patients without epidermodysplasia verruciformis. Clin Exp Dermatol. 2015;40:318-23 pubmed publisher
    Mutations of the EVER1 and EVER2 genes cause epidermodysplasia verruciformis (EV), a genodermatosis associated with squamous cell carcinoma (SCC). Recently, it has been found that the rs7208422 (c.917A→T, p...
  3. Sirianant L, Ousingsawat J, Tian Y, Schreiber R, Kunzelmann K. TMC8 (EVER2) attenuates intracellular signaling by Zn2+ and Ca2+ and suppresses activation of Cl- currents. Cell Signal. 2014;26:2826-33 pubmed publisher
    ..Mutations in TMC 6 and 8 (EVER1, EVER2) cause epidermodysplasia verruciformis...
  4. Liang C, Kelsey K, McClean M, Christensen B, Marsit C, Karagas M, et al. A coding variant in TMC8 (EVER2) is associated with high risk HPV infection and head and neck cancer risk. PLoS ONE. 2015;10:e0123716 pubmed publisher a rare condition of extreme susceptibility to cutaneous HPV infection primarily attributable to mutations in TMC6 and TMC8...
  5. Notarangelo L. HPV: CIB1 is for EVER and EVER. J Exp Med. 2018;215:2229-2231 pubmed publisher
    ..gene as a new cause of epidermodysplasia verruciformis (EV) and demonstrate that the CIB1 interacts with the EVER1 and EVER2 proteins to form a complex involved in keratinocyte-intrinsic immune response to human β-..
  6. Petiti J, Gutierrez S, De Paul A, Andreoli V, Palmeri C, Sosa L, et al. GH3B6 pituitary tumor cell proliferation is mediated by PKCalpha and PKCepsilon via ERK 1/2-dependent pathway. Cell Physiol Biochem. 2010;26:135-46 pubmed publisher
    ..induced by PMA in GH3B6 cells, an effect that was blocked by the inhibitors of PKCalpha (Gö6976) and PKCe (eV1-2)...
  7. Karjalainen M, Kakkonen E, Upla P, Paloranta H, Kankaanpää P, Liberali P, et al. A Raft-derived, Pak1-regulated entry participates in alpha2beta1 integrin-dependent sorting to caveosomes. Mol Biol Cell. 2008;19:2857-69 pubmed publisher
    We have previously shown that a human picornavirus echovirus 1 (EV1) is transported to caveosomes during 2 h together with its receptor alpha2beta1 integrin. Here, we show that the majority of early uptake does not occur through caveolae...
  8. de Jong S, Crequer A, Matos I, Hum D, Gunasekharan V, Lorenzo L, et al. The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. J Exp Med. 2018;215:2289-2310 pubmed publisher
    Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of TMC6 (encoding EVER1) or TMC8 (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-..
  9. Gomez Lucia E, Sanjosé L, Crespo O, Reina R, Glaria I, Ballesteros N, et al. Modulation of the long terminal repeat promoter activity of small ruminant lentiviruses by steroids. Vet J. 2014;202:323-8 pubmed publisher
    ..The presence of deletions and a 43 base repeat in the U3 region upstream of the TATA box of the LTR made strain EV1 less sensitive to DHEA...
  10. Crockett M, Murphy B, Smith J, Kavanagh E. Prevalence and clinical significance of extravascular incidental findings in patients undergoing CT cervico-cerebral angiography. Eur J Radiol. 2015;84:1569-1573 pubmed publisher
    ..findings were classified, according to an adaptation of the CT colonography data and reporting system (CRADS), as EV1-EV4...
  11. Tanomaru Filho M, Miano L, Chávez Andrade G, Torres F, Leonardo R, Guerreiro Tanomaru J. Cleaning of Root Canal System by Different Irrigation Methods. J Contemp Dent Pract. 2015;16:859-63 pubmed
    ..22 G needle at 5 mm short of working length-WL]; MI2-manual irrigation (30G needle at 2 mm short of WL); PUI; EV1-EndoVac (microcannula at 1 mm short of WL); EV2-Endovac (microcannula at 3 mm short of WL)...
  12. Martikainen M, Salorinne K, Lahtinen T, Malola S, Permi P, Häkkinen H, et al. Hydrophobic pocket targeting probes for enteroviruses. Nanoscale. 2015;7:17457-67 pubmed publisher
    ..Molecular modelling suggested that the probe fits the hydrophobic pockets of EV1 and CVA9, but not of CVB3 as expected, correlating well with the variations in the infectivity and stability of the ..
  13. Zuo X, Sun L, Yin X, Gao J, Sheng Y, Xu J, et al. Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis. Nat Commun. 2015;6:6793 pubmed publisher
    ..We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5...
  14. Przybyszewska J, Zlotogorski A, Ramot Y. Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate. J Am Acad Dermatol. 2017;76:1161-1175 pubmed publisher
    ..A breakthrough in our understanding of EV was the discovery that homozygous inactivating mutations in TMC6 (EVER1) and TMC8 (EVER2) determine susceptibility to this disorder; however, they have not solved all EV cases fully...
  15. Sorte H, Osnes L, Fevang B, Aukrust P, Erichsen H, Backe P, et al. A potential founder variant in CARMIL2/RLTPR in three Norwegian families with warts, molluscum contagiosum, and T-cell dysfunction. Mol Genet Genomic Med. 2016;4:604-616 pubmed
    ..diagnosis to CXCR4-,DOCK8-,GATA2-,MAGT1-,MCM4-,STK4-,RHOH-,TMC6-, and TMC8-related diseases...
  16. Li S, Duo L, Wang H, Dai W, Zhou E, Xu Y, et al. Identification of LCK mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma. Br J Dermatol. 2016;175:1204-1209 pubmed publisher
    ..Inactivating mutations in EVER1/EVER2 account for most cases of EV...
  17. de Souza M, Figueiredo M, de Baptista C, Aldaves R, Mattiello Sverzut A. Beneficial effects of ankle-foot orthosis daytime use on the gait of Duchenne muscular dystrophy patients. Clin Biomech (Bristol, Avon). 2016;35:102-10 pubmed publisher
    ..All subjects were evaluated once (Ev1) and five of them were re-evaluated between five and seven months after Ev1 (Ev2)...
  18. Olesen M, Jørgensen L, Blixenkrone Møller M, Sandberg E, Frandsen P, Østergaard E, et al. Screening for viral extraneous agents in live-attenuated avian vaccines by using a microbial microarray and sequencing. Biologicals. 2018;51:37-45 pubmed publisher
    ..of the positive microarray signals were most likely due to cross hybridization with the EAV-HP?pol and ALV-E ev1, ev3 and ev6 loci sequences originating from the chicken genome...
  19. Zuo Y, Ma D, Zhang Y, Qiao J, Wang B. Identification of a novel mutation and a genetic polymorphism of EVER1 gene in two families with epidermodysplasia verruciformis. J Dermatol Sci. 2006;44:153-9 pubmed
    ..The main clinical features include three kinds of lesions, high risk of skin cancer, and abnormal susceptibility to HPV 5 and 8. Recent studies have shown that mutations in EVER1 and EVER2 genes are responsible for the condition.
  20. Kurima K, Yang Y, Sorber K, Griffith A. Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis. Genomics. 2003;82:300-8 pubmed
    ..TMC6 and TMC8 are identical to the EVER1 and EVER2 genes implicated in epidermodysplasia verruciformis, a recessive disorder comprising susceptibility to ..
  21. Donfack J, Buchinsky F, Derkay C, Steinberg B, Choi S, Conley S, et al. Four mutations in Epidermodysplasia verruciformis 1 (EVER1) gene are not contributors to susceptibility in RRP. Int J Pediatr Otorhinolaryngol. 2006;70:1235-40 pubmed
    ..Recently four mutations in the Epidermodysplasia verruciformis 1 gene (EVER1, also known as TMC6) have been associated with the disease...
  22. Pohjolainen E, Malola S, Groenhof G, Häkkinen H. Exploring Strategies for Labeling Viruses with Gold Nanoclusters through Non-equilibrium Molecular Dynamics Simulations. Bioconjug Chem. 2017;28:2327-2339 pubmed publisher
    ..We have estimated the binding affinities of three different pocket factors of echovirus 1 (EV1) in molecular dynamics simulations combined with non-equilibrium free-energy calculations...
  23. Pavlidou E, Daponte A, Egea R, Dardiotis E, Hadjigeorgiou G, Barbadilla A, et al. Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer: a case control study. BMC Cancer. 2016;16:923 pubmed
    The aim of the study was to evaluate the association of two SNPs of EVER1/2 genes' region (rs2290907, rs16970849) and the FAS-670 polymorphism with the susceptibility to precancerous lesions and cervical cancer in a Greek population...
  24. O Blenes C, Pasternak S, Issekutz A, Gillis J, Chowdhury D, Finlayson L. Epidermodysplasia verruciformis in lipoid proteinosis: case report and discussion of pathophysiology. Pediatr Dermatol. 2015;32:118-21 pubmed publisher
    ..human papillomavirus (HPV) infections and squamous cell carcinoma, caused in most cases by homozygous mutations in EVER1 or EVER2. We describe a case of EV in a patient with LP and discuss the pathophysiology...
  25. Burger B, Spörri I, Stegmann D, De Mesmaker J, Schaub S, Itin P, et al. Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations. Dermatology. 2015;231:245-52 pubmed publisher
    ..Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC ..
  26. Hampras S, Rollison D, Tommasino M, Gheit T, Schabath M, Messina J, et al. Genetic variations in the epidermodysplasia verruciformis (EVER/TMC) genes, cutaneous human papillomavirus infection and squamous cell carcinoma of the skin. Br J Dermatol. 2015;173:1532-5 pubmed publisher
  27. Hachiya T, Komaki S, Hasegawa Y, Ohmomo H, Tanno K, Hozawa A, et al. Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA1c. Sci Rep. 2017;7:16147 pubmed publisher
    ..We identified 2 novel loci that achieved genome-wide significance: TMC6-TMC8 (P = 5.3 × 10-20) and SIX3-SIX2 (P = 8.6 × 10-9)...
  28. McDermott D, Gammon B, Snijders P, Mbata I, Phifer B, Howland Hartley A, et al. Autosomal dominant epidermodysplasia verruciformis lacking a known EVER1 or EVER2 mutation. Pediatr Dermatol. 2009;26:306-10 pubmed publisher
    ..Nonsense mutations in the genes EVER1 and EVER2 have been identified in over 75% of cases...
  29. Frecha C, Chevalier S, van Uden P, Rubio I, Siouda M, Saidj D, et al. Expression of the epidermodysplasia verruciformis-associated genes EVER1 and EVER2 is activated by exogenous DNA and inhibited by LMP1 oncoprotein from Epstein-Barr virus. J Virol. 2015;89:1461-7 pubmed publisher
    b>EVER1 and EVER2 are mutated in epidermodysplasia verruciformis patients, who are susceptible to human betapapillomavirus (HPV) infection. It is unknown whether their products control the infection of other viruses...
  30. Antonsson A, Law M, Neale R, Coman W, Pryor D, Porceddu S, et al. Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck. Cancer Causes Control. 2016;27:809-15 pubmed publisher
    ..Polymorphisms in the two EV genes (EVER1 and EVER2, also known as transmembrane channel protein (TMC) 6 and 8) have been identified as strong candidate ..
  31. Emond M, Louie T, Emerson J, Chong J, Mathias R, Knowles M, et al. Exome Sequencing of Phenotypic Extremes Identifies CAV2 and TMC6 as Interacting Modifiers of Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis. PLoS Genet. 2015;11:e1005273 pubmed publisher
    ..aeruginosa airway infection among individuals with CF and identified variants in CAV2 and TMC6 that were significantly associated with group status...
  32. Kwon E, Halvorson C, Rady P, Tyring S, Nguyen H, Kao G, et al. Merkel cell polyomavirus detection in a patient with familial epidermodysplasia verruciformis. Pediatr Dermatol. 2013;30:505-7 pubmed publisher
    ..We report a case of Merkel cell polyomavirus detection in the skin of a patient with epidermodysplasia verruciformis (EDV) and a family history remarkable for an unusual inheritance pattern for EDV. ..