{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T04:35:23Z","timestamp":1770957323570,"version":"3.50.1"},"reference-count":81,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15GM116089"],"award-info":[{"award-number":["R15GM116089"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glycine is an amino acid with unique properties because its side chain is composed of a single hydrogen atom. It confers conformational flexibility to proteins and conserved glycines are often indicative of protein domains involving tight turns or bends. All six beta-type connexins expressed in human epidermis (Cx26, Cx30, Cx30.3, Cx31, Cx31.1 and Cx32) contain a glycine at position 12 (G12). G12 is located about halfway through the cytoplasmic amino terminus and substitutions alter connexin function in a variety of ways, in some cases altering protein interactions and leading to cell death. There is also evidence that alteration of G12 changes the structure of the amino terminus in connexin- and amino acid- specific ways. This review integrates structural, functional and physiological information about the role of G12 in connexins, focusing on beta-connexins expressed in human epidermis. The importance of G12 substitutions in these beta-connexins is revealed in two hereditary skin disorders, keratitis ichthyosis and erythrokeratodermia variabilis, both of which result from missense mutations affecting G12.<\/jats:p>","DOI":"10.3390\/ijms22052615","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:03:15Z","timestamp":1614920595000},"page":"2615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Complex and Critical Role of Glycine 12 (G12) in Beta-Connexins of Human Skin"],"prefix":"10.3390","volume":"22","author":[{"given":"Rasheed A.","family":"Bailey","sequence":"first","affiliation":[{"name":"Biology Department, SUNY Buffalo State, 1300 Elmwood Ave, Buffalo, NY 14222, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek L.","family":"Beahm","sequence":"additional","affiliation":[{"name":"Biology Department, SUNY Buffalo State, 1300 Elmwood Ave, Buffalo, NY 14222, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. Martha","family":"Skerrett","sequence":"additional","affiliation":[{"name":"Biology Department, SUNY Buffalo State, 1300 Elmwood Ave, Buffalo, NY 14222, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cardiores.2003.11.013","article-title":"Gap junctions and the connexin protein family","volume":"62","author":"Willecke","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3109\/15419060109080718","article-title":"Cloning and Functional Expression of a Novel Human Connexin-25 Gene","volume":"8","author":"Bondarev","year":"2001","journal-title":"Cell Commun. Adhes."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1046\/j.0022-202x.2001.01468.x","article-title":"Multiple Epidermal Connexins are Expressed in Different Keratinocyte Subpopulations Including Connexin 31","volume":"117","author":"Di","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"Sievers","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20911","DOI":"10.1074\/jbc.M111498200","article-title":"Targeted gap junction protein constructs reveal connexin-specific differences in oligomerization","volume":"277","author":"Wang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1042\/BJ20051922","article-title":"Life cycle of connexins in health and disease","volume":"394","author":"Laird","year":"2006","journal-title":"Biochem. J."},{"key":"ref_7","first-page":"689","article-title":"The skin\u2019s barrier","volume":"144","author":"Jensen","year":"2009","journal-title":"G Ital. Dermatol. Venereol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1387\/ijdb.170341fw","article-title":"Homeostasis, regeneration and tumour formation in the mammalian epidermis","volume":"62","author":"Belokhvostova","year":"2018","journal-title":"Int. J. Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/j.1600-0625.2008.00786.x","article-title":"The skin: An indispensable barrier","volume":"17","author":"Proksch","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.semcdb.2015.11.018","article-title":"Connexin channels in congenital skin disorders","volume":"50","author":"Lilly","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3389\/fphys.2016.00596","article-title":"The Role of Connexins in Wound Healing and Repair: Novel Therapeutic Approaches","volume":"7","author":"Wong","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00441-014-2094-3","article-title":"Connexins and skin disease: Insights into the role of beta connexins in skin homeostasis","volume":"360","author":"Martin","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1086\/339986","article-title":"Missense Mutations in GJB2 Encoding Connexin-26 Cause the Ectodermal Dysplasia Keratitis-Ichthyosis-Deafness Syndrome","volume":"70","author":"Richard","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1046\/j.1365-2133.2000.03292.x","article-title":"Refined localization of the gene for Clouston syndrome (hidrotic ectodermal dysplasia) in a large French family","volume":"142","author":"Lamartine","year":"2000","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1046\/j.1523-1747.2003.12080.x","article-title":"Genetic Heterogeneity in Erythrokeratodermia Variabilis: Novel Mutations in the Connexin Gene GJB4 (Cx30.3) and Genotype-Phenotype Correlations","volume":"120","author":"Richard","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/3840","article-title":"Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis","volume":"20","author":"Richard","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/humu.9220","article-title":"A homozygousGJA1 gene mutation causes a Hallermann-Streiff\/ODDD spectrum phenotype","volume":"23","author":"Pizzuti","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/ajmg.a.31558","article-title":"Skin changes in oculo-dento-digital dysplasia are correlated with C-terminal truncations of connexin 43","volume":"143","author":"Vreeburg","year":"2007","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"Stenson","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12881-018-0650-5","article-title":"Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia","volume":"19","author":"Zytsar","year":"2018","journal-title":"BMC Med. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1001\/archotol.127.9.1037","article-title":"Connexin 26 Studies in Patients with Sensorineural Hearing Loss","volume":"127","author":"Kenna","year":"2001","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0006-291X(02)00891-4","article-title":"Hearing loss: Frequency and functional studies of the most common connexin26 alleles","volume":"296","author":"Veronesi","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/jid.2015.20","article-title":"Keratitis-Ichthyosis-Deafness Syndrome-Associated Cx26 Mutants Produce Nonfunctional Gap Junctions but Hyperactive Hemichannels When Co-Expressed With Wild Type Cx43","volume":"135","author":"Jara","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.jid.2015.11.017","article-title":"From Hyperactive Connexin26 Hemichannels to Impairments in Epidermal Calcium Gradient and Permeability Barrier in the Keratitis-Ichthyosis-Deafness Syndrome","volume":"136","author":"Bosen","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/jid.2008.335","article-title":"Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes","volume":"129","author":"Lee","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1525-1470.2011.01425.x","article-title":"Extending the Phenotypic Spectrum of Keratitis-Ichthyosis-Deafness Syndrome: Report of a Patient with GJB2 (G12R) Connexin 26 Mutation and Unusual Clinical Findings","volume":"29","author":"Lazic","year":"2012","journal-title":"Pediatr. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12824","DOI":"10.1038\/s41598-018-30757-3","article-title":"Roles of aberrant hemichannel activities due to mutant connexin26 in the pathogenesis of KID syndrome","volume":"8","author":"Taki","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1042\/BJ20110278","article-title":"Key functions for gap junctions in skin and hearing","volume":"438","author":"Scott","year":"2011","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/ajmg.a.32744","article-title":"The missense mutation G12D in connexin30.3 can cause both erythrokeratodermia variabilis of Mendes da Costa and progressive symmetric erythrokeratodermia of Gottron","volume":"149A","author":"Oranje","year":"2009","journal-title":"Am. J. Med. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1093\/hmg\/11.17.2005","article-title":"Defective trafficking and cell death is characteristic of skin disease-associated connexin 31 mutations","volume":"11","author":"Di","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1111\/ajd.12887","article-title":"Exome sequencing identifies novel compound heterozygous mutations in GJB3 gene that cause erythrokeratodermia variabilis et progressiva","volume":"60","author":"Deng","year":"2019","journal-title":"Australas. J. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1034\/j.1600-0625.2003.120210.x","article-title":"Divergent effects of two sequence variants of GJB3 (G12D and R32W) on the function of connexin 31 in vitro","volume":"12","author":"Rouan","year":"2003","journal-title":"Exp. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1745-7270.2005.00080.x","article-title":"Intracellular Distribution, Assembly and Effect of Disease-associated Connexin 31 Mutants in HeLa Cells","volume":"37","author":"He","year":"2005","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1529-8027.2012.00424.x","article-title":"X-linked Charcot-Marie-Tooth disease","volume":"17","author":"Scherer","year":"2012","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9077","DOI":"10.1523\/JNEUROSCI.17-23-09077.1997","article-title":"Altered Trafficking of Mutant Connexin32","volume":"17","author":"Walcott","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1006\/nbdi.1997.0152","article-title":"Connexin32 and X-linked Charcot\u2013Marie\u2013Tooth Disease","volume":"4","author":"Bone","year":"1997","journal-title":"Neurobiol. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0006-8993(00)03327-8","article-title":"Functional alterations in gap junction channels formed by mutant forms of connexin 32: Evidence for loss of function as a pathogenic mechanism in the X-linked form of Charcot-Marie-Tooth disease","volume":"900","author":"Abrams","year":"2001","journal-title":"Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1126\/science.283.5405.1176","article-title":"Three-dimensional structure of a recombinant gap junction membrane channel","volume":"283","author":"Unger","year":"1999","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10034","DOI":"10.1073\/pnas.0703704104","article-title":"Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule","volume":"104","author":"Oshima","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nature07869","article-title":"Structure of the connexin 26 gap junction channel at 3.5 A resolution","volume":"458","author":"Maeda","year":"2009","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8770","DOI":"10.1038\/ncomms9770","article-title":"An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels","volume":"7","author":"Bennett","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41586-018-0786-7","article-title":"Structure of native lens connexin 46\/50 intercellular channels by cryo-EM","volume":"564","author":"Myers","year":"2018","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0070-2161(08)61016-3","article-title":"Mechanistic Differences Between Chemical and Electrical Gating of Gap Junctions","volume":"Volume 49","author":"Peracchia","year":"1999","journal-title":"Current Topics in Membranes"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/bip.20960","article-title":"Roles of beta-turns in protein folding: From peptide models to protein engineering","volume":"89","author":"Marcelino","year":"2008","journal-title":"Biopolymers"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/368348a0","article-title":"Opposite voltage gating polarities of two closely related connexins","volume":"368","author":"Verselis","year":"1994","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1016\/S0006-3495(00)76485-X","article-title":"Reversal of the Gating Polarity of Gap Junctions by Negative Charge Substitutions in the N-Terminus of Connexin 32","volume":"79","author":"Purnick","year":"2000","journal-title":"Biophys. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1242\/jcs.032482","article-title":"An intact connexin N-terminus is required for function but not gap junction formation","volume":"121","author":"Kyle","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/j.bbamem.2011.10.011","article-title":"Structural organization of intercellular channels II. Amino terminal domain of the connexins: Sequence, functional roles, and structure","volume":"1818","author":"Beyer","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2012.05.027","article-title":"Structural studies of N-terminal mutants of Connexin 32 using (1)H NMR spectroscopy","volume":"526","author":"Kalmatsky","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1080\/19336950.2016.1200775","article-title":"Specificity of the connexin W3\/4 locus for functional gap junction formation","volume":"10","author":"Xu","year":"2016","journal-title":"Channels"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.bbamem.2011.09.019","article-title":"Voltage-dependent conformational changes in connexin channels","volume":"1818","author":"Bargiello","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Villanelo, F., Escalona, Y., Pareja-Barrueto, C., Garate, J.A., Skerrett, I.M., and Perez-Acle, T. (2017). Accessing gap-junction channel structure-function relationships through molecular modeling and simulations. BMC Cell Biol., 18.","DOI":"10.1186\/s12860-016-0121-9"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1006\/abbi.2000.1989","article-title":"Structure of the Amino Terminus of a Gap Junction Protein","volume":"381","author":"Purnick","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.abb.2016.06.019","article-title":"Structural studies of N-terminal mutants of Connexin 26 and Connexin 32 using (1)H NMR spectroscopy","volume":"608","author":"Batir","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jaad.2003.12.042","article-title":"A novel connexin 26 gene mutation associated with features of the keratitis-ichthyosis-deafness syndrome and the follicular occlusion triad","volume":"51","author":"Montgomery","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1152\/physrev.00007.2003","article-title":"Plasma membrane channels formed by connexins: Their Regulation and Functions","volume":"83","author":"Saez","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1038\/sj.jid.5700770","article-title":"Gap Junctions: Basic Structure and Function","volume":"127","author":"Richard","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1001\/archderm.1981.01650050041019","article-title":"The Keratitis, Ichthyosis, and Deafness (KID) Syndrome","volume":"117","author":"Skinner","year":"1981","journal-title":"Arch. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/387080a0","article-title":"Connexin 26 mutations in hereditary non-syndromic sensorineural deafness","volume":"387","author":"Kelsell","year":"1997","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/S0140-6736(98)11071-1","article-title":"Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: Implications for genetic counselling","volume":"353","author":"Denoyelle","year":"1999","journal-title":"Lancet"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1111\/j.1365-4632.2009.04136.x","article-title":"A rare connexin 26 mutation in a patient with a forme fruste of keratitis-ichthyosis-deafness (KID) syndrome","volume":"48","author":"Neoh","year":"2009","journal-title":"Int. J. Dermatol."},{"key":"ref_62","first-page":"40","article-title":"Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene","volume":"106","author":"Rabionet","year":"2000","journal-title":"Hum. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/j.1600-0625.2012.01521.x","article-title":"Differential susceptibility of Cx26 mutations associated with epidermal dysplasias to peptidoglycan derived from Staphylococcus aureus and Staphylococcus epidermidis","volume":"21","author":"Donnelly","year":"2012","journal-title":"Exp. Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1242\/jcs.00604","article-title":"Specific amino-acid residues in the N-terminus and TM3 implicated in channel function and oligomerization compatibility of connexin43","volume":"116","author":"Brunschwig","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1085\/jgp.201711782","article-title":"The syndromic deafness mutation G12R impairs fast and slow gating in Cx26 hemichannels","volume":"150","author":"Villanelo","year":"2018","journal-title":"J. Gen. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1086\/497996","article-title":"GJB2 Mutations and Degree of Hearing Loss: A Multicenter Study","volume":"77","author":"Snoeckx","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/BF00186783","article-title":"Gap junctions in the rat cochlea: Immunohistochemical and ultrastructural analysis","volume":"191","author":"Kikuchi","year":"1995","journal-title":"Anat. Embryol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/bmb\/63.1.73","article-title":"Hereditary deafness and phenotyping in humans","volume":"63","year":"2002","journal-title":"Br. Med. Bull."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/j.1346-8138.2009.00768.x","article-title":"G11R mutation in GJB6 gene causes hidrotic ectodermal dysplasia involving only hair and nails in a Chinese family","volume":"37","author":"Chen","year":"2010","journal-title":"J. Dermatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1093\/hmg\/ddh191","article-title":"Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity","volume":"13","author":"Essenfelder","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1093\/hmg\/ddg364","article-title":"Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with erythrokeratodermia variabilis","volume":"12","author":"Plantard","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1093\/hmg\/10.9.947","article-title":"Connexin 31 (GJB3) is expressed in the peripheral and auditory nerves and causes neuropathy and hearing impairment","volume":"10","author":"Olive","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0006-291X(02)00929-4","article-title":"Expression of a connexin31 mutation causing erythrokeratodermia variabilis is lethal for HeLa cells","volume":"296","author":"Diestel","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4734","DOI":"10.1093\/hmg\/ddp436","article-title":"EKV mutant connexin 31 associated cell death is mediated by ER stress","volume":"18","author":"Tattersall","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chi, J., Li, L., Liu, M., Tan, J., Tang, C., Pan, Q., Wang, D., and Zhang, Z. (2012). Pathogenic Connexin-31 Forms Constitutively Active Hemichannels to Promote Necrotic Cell Death. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032531"},{"key":"ref_76","unstructured":"Bailey, R. (2000). Functional Analysis of a Critical Glycine (Glycine 12) in Beta-type Connexins of Human Skin. Biology. [Master\u2019s Thesis, The State University of New York College at Buffalo\u2013Buffalo State Collage]. Available online: https:\/\/digitalcommons.buffalostate.edu\/biology_theses\/41."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/3845","article-title":"Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment","volume":"20","author":"Xia","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1126\/science.8266101","article-title":"Connexin mutations in X-linked Charcot-Marie-Tooth disease","volume":"262","author":"Bergoffen","year":"1993","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1006\/nbdi.2002.0545","article-title":"Diverse Trafficking Abnormalities of Connexin32 Mutants Causing CMTX","volume":"11","author":"Yum","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Garc\u00eda, I.E., Prado, P., Pupo, A., Jara, O., Rojas-G\u00f3mez, D., Mujica, P., Flores-Mu\u00f1oz, C., Gonz\u00e1lez-Casanova, J., Soto-Riveros, C., and Pinto, B.I. (2016). Connexinopathies: A structural and functional glimpse. BMC Cell Biol., 17.","DOI":"10.1186\/s12860-016-0092-x"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.bbrc.2010.03.073","article-title":"Connexin 26 (GJB2) mutations, causing KID Syndrome, are associated with cell death due to calcium gating deregulation","volume":"394","author":"Terrinoni","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2615\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:19Z","timestamp":1760160799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":81,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052615"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052615","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}