Gene Symbol: TMC8
Description: transmembrane channel like 8
Alias: EV2, EVER2, EVIN2, transmembrane channel-like protein 8, epidermodysplasia verruciformis 2, epidermodysplasia verruciformis protein 2
Species: human
Products:     TMC8

Top Publications

  1. 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 skin ..
  2. 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...
  3. 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 cutaneous ..
  4. 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
    ..analysis allowed to map a candidate region for a second epidermodysplasia verruciformis susceptibility locus (EV2) within the 8 cM interval between markers D2S171 and D2S2347 of the 2p21-p24 region...
  5. Gaud G, Guillemot D, Jacob Y, Favre M, Vuillier F. EVER2 protein binds TRADD to promote TNF-?-induced apoptosis. Cell Death Dis. 2013;4:e499 pubmed publisher
    ..We show here that EVER2 induces TNF-?- and TRAIL-dependant apoptosis...
  6. 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), a ..
  7. Arnold A, Burger B, Kump E, Rufle A, Tyring S, Kempf W, et al. Homozygosity for the c.917A?T (p.N306l) polymorphism in the EVER2/TMC8 gene of two sisters with epidermodysplasia verruciformis Lewandowsky-Lutz originally described by Wilhelm Lutz. Dermatology. 2011;222:81-6 pubmed publisher
    ..On chromosome 17, 2 adjacent related genes--EVER1/TMC6 and EVER2/TMC8--were identified...
  8. 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...
  9. 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
    ..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 ..

More Information


  1. Girijala R, Nyinawinyange D, Parekh P, Grimwood R. Multiple flat-topped scaly violaceous papules. Dermatol Online J. 2019;25: pubmed
    ..Owing to TMC6/EVER1 and TMC8/EVER2 mutations that lead to abnormal transmembrane channels in the endoplasmic reticulum involved in immunological ..
  2. 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
    ..Similarly, the second eigenvector represented infection resilience/resistance (EV2, 22%; high WG, low CLS and high IL-10), and the third eigenvector tolerance (EV3, 19%; high WG, high CLS and low IL-..
  3. 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 infections, ..
  4. 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
    ..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-papillomaviruses (β-HPVs),..
  5. Notarangelo L. HPV: CIB1 is for EVER and EVER. J Exp Med. 2018;215:2229-2231 pubmed publisher 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-papillomaviruses (β-..
  6. 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
    ..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)...
  7. 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
    ..i>CXCR4-,DOCK8-,GATA2-,MAGT1-,MCM4-,STK4-,RHOH-,TMC6-, and TMC8-related diseases...
  8. 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)...
  9. 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
    ..EV1=no incidental findings, EV2=clinically insignificant incidental finding, EV3=incidental finding of intermediate clinical significance, EV4=..
  10. 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 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...
  11. 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...
  12. Guo W, Chen X, Zhu L, Wang Q. A six-mRNA signature model for the prognosis of head and neck squamous cell carcinoma. Oncotarget. 2017;8:94528-94538 pubmed publisher
    ..The patients were divided into the training and testing sets. A model of six mRNAs (FRMD5, PCMT1, PDGFA, TMC8, YIPF4, ZNF324B) that could predict patient prognosis was identified in the training set using the Cox regression ..
  13. 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...
  14. 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...
  15. 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
    ..None of the SNPs included in the study can be associated with statistical significance with the development of precancerous lesions or cervical cancer. ..
  16. 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
    ..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...
  17. Zavattaro E, Azzimonti B, Mondini M, de Andrea M, Borgogna C, Dell Oste V, et al. Identification of defective Fas function and variation of the perforin gene in an epidermodysplasia verruciformis patient lacking EVER1 and EVER2 mutations. J Invest Dermatol. 2008;128:732-5 pubmed
  18. Rady P, de Oliveira W, He Q, Festa C, Rivitti E, Tucker S, et al. Novel homozygous nonsense TMC8 mutation detected in patients with epidermodysplasia verruciformis from a Brazilian family. Br J Dermatol. 2007;157:831-3 pubmed
  19. Landini M, Zavattaro E, Borgogna C, Azzimonti B, de Andrea M, Colombo E, et al. Lack of EVER2 protein in two epidermodysplasia verruciformis patients with skin cancer presenting previously unreported homozygous genetic deletions in the EVER2 gene. J Invest Dermatol. 2012;132:1305-8 pubmed publisher
  20. 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
    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...
  21. 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...
  22. 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
  23. 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 genes, since ..
  24. Vuillier F, Gaud G, Guillemot D, Commere P, Pons C, Favre M. Loss of the HPV-infection resistance EVER2 protein impairs NF-?B signaling pathways in keratinocytes. PLoS ONE. 2014;9:e89479 pubmed publisher
    ..The effects of EVER protein loss on the keratinocyte immune response remain unknown. We show here that EVER2 plays a critical role in the interplay between the NF-?B and JNK/AP-1 signaling pathways...
  25. 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. ..
  26. Patel A, Karagas M, Pawlita M, Waterboer T, Nelson H. Cutaneous human papillomavirus infection, the EVER2 gene and incidence of squamous cell carcinoma: a case-control study. Int J Cancer. 2008;122:2377-9 pubmed publisher
    ..Two EV genes (EVER1 and EVER2) have been identified, and we tested the hypothesis that variation in the EVER2 gene (rs7208422) is related to ..
  27. 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 development, contain ..
  28. 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
    ..rare condition of extreme susceptibility to cutaneous HPV infection primarily attributable to mutations in TMC6 and TMC8. Genetic variation in the TMC6/TMC8 region has been linked to beta-type HPV infection and squamous cell carcinoma ..
  29. 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)...
  30. Crequer A, Picard C, Pedergnana V, Lim A, Zhang S, Abel L, et al. EVER2 deficiency is associated with mild T-cell abnormalities. J Clin Immunol. 2013;33:14-21 pubmed publisher
    ..Autosomal recessive EVER1 and EVER2 deficiencies account for EV in most patients...