Affinage

Showing GJB2 — CX26 is a alias.

GJB2

Gap junction beta-2 protein · UniProt P29033

Length
226 aa
Mass
26.2 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GJB2 encodes connexin 26 (Cx26), a four-transmembrane connexin-family protein that oligomerizes into hemichannels and intercellular gap junction channels mediating direct cell-cell exchange of small molecules and ions (PMID:2557354). Cx26 reaches the plasma membrane through the Golgi-dependent secretory pathway shared with Cx43, but is delivered via actin-dependent, largely microtubule-independent post-Golgi carriers and is more mobile within gap junction plaques than Cx43 (PMID:12064594, PMID:16159960). It localizes to gap junction plaques in diverse epithelia and glia, where it can co-assemble with Cx30 and Cx43 in shared plaques (PMID:12064610). Channel gating is controlled by CO2 through residues K125 and R104, which favor gap junction closure while promoting hemichannel opening, independently of pH (PMID:33022747). In the cochlea, Cx26 forms heterologous gap junctions with Cx30 in the lateral wall connective tissue to maintain the endocochlear potential, and partial loss triggers oxidative damage, reduced glutathione/hemichannel release and Nrf2-pathway dysregulation driving accelerated hearing loss; Cx26 is also required postnatally for cytoskeletal development of the organ of Corti (PMID:28823936, PMID:30199819, PMID:29361521). Recessive non-syndromic deafness (DFNB1) arises from loss-of-function mutations acting through impaired trafficking (D66H, T55N), reduced channel conductance (M34T), or complete channel failure (R143W, V153I, L214P), several of which additionally exert dominant-negative inhibition of co-expressed Cx26, Cx30, Cx32 or Cx43; large upstream deletions reduce GJB2 expression in cis via a distant cis-regulatory element (PMID:14978038, PMID:15241677, PMID:16849369, PMID:16226720, PMID:20236118). In contrast, syndromic KID-syndrome mutations (D50N, D50A, A88V, G12R) cause gain-of-hemichannel-function through aberrant gating and loss of Ca2+-dependent inhibition (PMID:23797419, PMID:23447037, PMID:29643172). Beyond its channel roles, Cx26 also functions as a negative regulator of airway basal-cell proliferation and, in triple-negative breast cancer stem cells, forms a NANOG–FAK signaling complex driving self-renewal independently of channel function (PMID:24569117, PMID:29422613).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 High

    Establishing that GJB2 encodes a bona fide connexin defined the protein's identity and predicted its role in gap junctional communication across many tissues.

    Evidence cDNA cloning, sequence/structure analysis and Northern blot tissue survey

    PMID:2557354

    Open questions at the time
    • No functional channel assay in the cloning study
    • Cochlear expression and deafness role not yet addressed
  2. 1998 Medium

    Identifying PKC/AP1-dependent transcriptional induction of GJB2 answered how Cx26 expression is regulated, linking it to signaling-responsive gene control.

    Evidence Nuclear run-on, DNase I hypersensitivity mapping, EMSA and CAT reporter assays with PKC inhibition in mammary epithelial cells

    PMID:9524250

    Open questions at the time
    • Regulatory element activity tested in reporter context only
    • Relevance to cochlear or disease expression not established
  3. 2001 High

    Localizing Cx26 to specific glial gap junction plaques and showing actin-dependent, microtubule-independent plaque recruitment distinguished its trafficking from Cx43 and clarified where it operates.

    Evidence FRIL/confocal immunolocalization in rat CNS and FRAP with cytoskeletal drug disruption in NRK cells expressing Cx26-YFP

    PMID:12064594 PMID:12064610

    Open questions at the time
    • Mechanism coupling actin to plaque recruitment unresolved
    • Trafficking inferred from tagged constructs in heterologous cells
  4. 2005 High

    Defining the Golgi-dependent secretory route and Sar1/microtubule requirements established the Cx26 delivery pathway and its divergence from Cx43.

    Evidence Live-cell imaging of tagged connexins with brefeldin A, dominant-negative Sar1, nocodazole and FRAP

    PMID:16159960

    Open questions at the time
    • Specific carrier motor/adaptor proteins not identified
    • Performed in non-cochlear cell lines
  5. 2006 High

    Functional dissection of recessive deafness mutations revealed multiple distinct loss-of-function mechanisms—trafficking block, pore constriction, complete channel failure—rather than a single defect.

    Evidence Xenopus oocyte electrophysiology, HeLa dye transfer/Ca2+ wave imaging, mutant trafficking and structural modeling across mutation panels

    PMID:14681041 PMID:14978038 PMID:15241677 PMID:16226720 PMID:16300957 PMID:16849369

    Open questions at the time
    • Genotype-phenotype severity correlations incomplete
    • Most assays in heterologous systems, not cochlea
  6. 2005 Medium

    Demonstrating allele-specific RNAi rescue of a dominant-negative mutant in vivo answered whether targeted silencing could prevent connexin deafness.

    Evidence In vitro and in vivo siRNA against the R75W allele in a mouse cochlear model with hearing readout

    PMID:15857852

    Open questions at the time
    • Durability and delivery efficiency not fully characterized
    • Single allele tested
  7. 2011 High

    Mapping large upstream deletions that reduce GJB2 mRNA in cis established a distant cis-regulatory element controlling GJB2 (and GJB6) expression.

    Evidence Array CGH deletion mapping and allele-specific RT-PCR expression assays in DFNB1 kindreds and probands

    PMID:20236118 PMID:21738759

    Open questions at the time
    • Identity and binding factors of the regulatory element undefined
    • Mechanism of dual GJB2/GJB6 control unresolved
  8. 2013 High

    Showing that KID-syndrome mutations create overactive hemichannels with lost Ca2+ inhibition defined a gain-of-function mechanism distinct from deafness loss-of-function.

    Evidence Hemichannel and gap junction electrophysiology with site-directed mutagenesis across oocytes, HeLa and primary keratinocytes

    PMID:23447037 PMID:23797419

    Open questions at the time
    • In vivo skin phenotype causality not directly tested
    • Pore-residue interactions partly model-dependent
  9. 2017 High

    Cell-type-specific double-heterozygous knockouts placed Cx26/Cx30 heterologous coupling in the cochlear lateral wall as the basis for endocochlear potential maintenance and defined a redox/Nrf2 pathway for partial loss.

    Evidence Conditional knockout and Gjb2+/- mouse models with EP measurement, ABR/DPOAE, glutathione and Nrf2 pathway analysis

    PMID:28823936 PMID:30199819

    Open questions at the time
    • Molecular link between hemichannel glutathione release and Nrf2 not fully mapped
    • Redox mechanism from single lab
  10. 2018 High

    Three studies expanded Cx26 biology: a molecular gating mechanism for KID gain-of-function, a postnatal cytoskeletal role in the organ of Corti, and a non-channel oncogenic signaling complex.

    Evidence Single-channel electrophysiology with MD simulations (G12R); conditional Gjb2 knockdown with cochlear histology/acetylated tubulin; reciprocal Co-IP and rescue in TNBC cancer stem cells

    PMID:29361521 PMID:29422613 PMID:29643172

    Open questions at the time
    • NANOG/FAK complex from single lab without structural detail
    • Cytoskeletal mechanism downstream of Cx26 unknown
  11. 2020 High

    Identifying K125/R104 carbamylation as the CO2 sensor explained how a single mechanism oppositely gates gap junctions and hemichannels independently of pH.

    Evidence Dye transfer, whole-cell patch clamp, site-directed mutagenesis and elastic network modeling with CO2 manipulation

    PMID:33022747

    Open questions at the time
    • Physiological context of CO2 gating in cochlea unaddressed
    • Structural basis of carbamylation site inferred from modeling
  12. 2023 Medium

    A 35delG/35delG mouse confirmed that the most common deafness allele impairs cochlear gap junction formation/function rather than hair cell survival, validating the channel-loss disease model.

    Evidence Tetraploid embryo complementation/semi-cloning mouse model with ABR and cochlear gap junction functional analysis

    PMID:37178259

    Open questions at the time
    • Downstream sequence from junction failure to deafness not fully traced
    • Single model system

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Cx26's channel-dependent and channel-independent (NANOG/FAK signaling) functions are coordinated, and the identity of the cis-regulatory and trafficking machinery controlling Cx26, remain open.
  • No structural model of the NANOG–FAK–Cx26 complex
  • Trafficking adaptors and the upstream regulatory element are unidentified
  • In vivo relevance of CO2 gating untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0005198 structural molecule activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 4 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-1500931 Cell-Cell communication 2 R-HSA-9709957 Sensory Perception 2
Partners
GJA1GJB1GJB6NANOGPTK2
Complex memberships
Cx26 gap junction plaqueCx26-NANOG-FAK signaling complexCx26/Cx30 heterotypic gap junction

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 Cx26 (GJB2) was identified as a second hepatic gap junction protein with a calculated molecular mass of 26,453 Da. cDNA cloning revealed overall sequence homology with Cx32 and Cx43 (64% and 51% amino acid identity, respectively) and a similar predicted four-transmembrane tertiary structure, confirming it as a connexin family member. Northern blots showed Cx26 mRNA is co-expressed with Cx32 in liver, kidney, intestine, lung, spleen, stomach, testes, and brain, but not in heart or adult skeletal muscle. cDNA cloning, Northern blot, sequence/structural analysis The Journal of cell biology High 2557354
2001 In rat CNS, Cx26 (along with Cx30 and Cx43) was localized exclusively to astrocyte gap junctions by freeze-fracture replica immunogold labeling (FRIL) and confocal immunocytochemistry. Cx26 was co-localized with Cx30 and Cx43 within individual gap junction plaques of astrocytes. In oligodendrocyte–astrocyte heterologous junctions, Cx26/Cx30/Cx43 were present on the astrocyte side and Cx32 on the oligodendrocyte side, defining separate glial communication pathways. Freeze-fracture replica immunogold labeling (FRIL), confocal immunocytochemistry Cell communication & adhesion High 12064610
2001 Cx26-YFP recruitment into gap junction plaques requires intact actin microfilaments (disruption by cytochalasin B abolished recruitment) but, unlike Cx43-GFP, was not dependent on intact microtubules (nocodazole had limited effect). FRAP showed that Cx26-YFP recovered into photobleached gap junction areas within 2 hours in untreated cells. Fluorescence recovery after photobleaching (FRAP), cytoskeletal drug disruption (cytochalasin B, nocodazole) in NRK cells expressing Cx26-YFP Cell communication & adhesion Medium 12064594
2004 The D66H Cx26 mutant (associated with deafness and skin disease) was retained within the brefeldin A-insensitive trans-Golgi network and failed to form functional gap junctions permeable to small dyes. G59A Cx26 reached the cell surface but also failed to form permeable gap junctions. Both G59A and D66H exerted dominant-negative effects on co-expressed wild-type Cx26; G59A also trans-dominantly inhibited Cx32 and Cx43, whereas D66H trans-dominantly inhibited Cx43 but not Cx32. Systematic mutagenesis at D66 showed that the first extracellular loop is critical for Cx26 transport and channel function. GFP-tagged Cx26 mutant expression in HeLa cells, brefeldin A treatment, Lucifer Yellow dye transfer assay, co-expression with wild-type connexins The Journal of biological chemistry High 14978038
2005 Cx26 and Cx43 share common secretory pathways to the plasma membrane via the Golgi apparatus (both inhibited by brefeldin A and dominant-negative Sar1 GTPase). Both connexins use heterogeneous post-Golgi carriers (vesicles and tubular extensions). However, Cx43-GFP delivery required intact microtubules (inhibited by nocodazole), whereas Cx26-GFP delivery did not. FRAP also revealed that Cx26-YFP was more mobile within gap junction plaques than Cx43-GFP. Time-lapse live-cell fluorescence imaging of GFP/YFP-tagged connexins, brefeldin A treatment, dominant-negative Sar1, nocodazole treatment, FRAP in BICR-M1Rk and NRK cells Journal of cell science High 16159960
2004 Five Cx26 mutations (R143W, V153I, L214P, T8M, N206S) associated with recessive non-syndromic hearing loss were functionally tested in the paired Xenopus oocyte assay. R143W, V153I, and L214P completely abolished channel function. T8M and N206S formed functional channels with altered voltage-gating properties, suggesting deafness from these mutations may not solely result from reduced K+ re-circulation but also from abnormal exchange of other metabolites. Paired Xenopus oocyte electrophysiology assay Human genetics Medium 15241677
2005 In vitro and in vivo RNAi targeting GJB2 selectively suppressed the dominant-negative R75W mutant allele by >70% in a mouse model without affecting endogenous murine Gjb2 expression, preventing hearing loss. This demonstrated that allele-specific post-transcriptional silencing of GJB2 is feasible in vivo. siRNA transfection in mammalian cells; in vivo siRNA delivery in mouse cochlea; qRT-PCR for expression quantification Human molecular genetics Medium 15857852
2005 Loss-of-function GJB2 mutations were characterized by Xenopus oocyte hemichannel conductance assays. Co-expression with wild-type Cx26 showed that M34T, V37I, and I82M (but not G59V, L90P, R127H, and R143W) exerted dominant inhibitory effects. When co-expressed with Cx30, all tested mutants had a dominant inhibitory effect on Cx30-mediated coupling. Xenopus oocyte depolarization-activated conductance assay; co-expression with wild-type Cx26 and Cx30 Neurobiology of disease Medium 16300957
2006 The M34T Cx26 mutation was correctly synthesized and trafficked to the plasma membrane but formed intercellular channels with only 11% of wild-type unitary conductance, failed to support Lucifer Yellow diffusion or intercellular Ca2+ wave spreading, and exerted dominant-negative effects when co-expressed with wild-type Cx26. Structural modeling predicted M34T causes a constriction of the channel pore. HeLa cell transfection, electrophysiology (cell coupling), Lucifer Yellow dye transfer, Ca2+ wave imaging, structural modeling; genetic and audiological data Human molecular genetics High 16849369
2006 A novel GJB2 missense mutation T55N, located at the apex of the first extracellular loop, produces a protein expressed at wild-type levels but deeply impaired in intracellular trafficking, failing to reach the plasma membrane—establishing the first extracellular loop as a critical domain for Cx26 targeting. Expression of GFP-tagged Cx26-T55N in mammalian cells, subcellular localization imaging Biochemical and biophysical research communications Medium 16226720
2010 A 131.4 kb deletion whose proximal breakpoint lies >100 kb upstream of the GJB2 and GJB6 transcriptional start sites segregates as a fully penetrant DFNB1 allele and reduces expression of both GJB2 and GJB6 mRNA from the affected allele, providing direct evidence for a distant cis-regulatory element controlling both genes. Array comparative genomic hybridization (array CGH), allele-specific expression assay (RT-PCR) Clinical genetics High 20236118
2011 The del(GJB6-D13S1854) deletion, similar to del(GJB6-D13S1830), causes allele-specific loss of GJB2 mRNA expression in cis (while retaining minimal residual expression), by removing putative cis-regulatory element(s) upstream of GJB6. This was demonstrated by allele-specific RT-PCR and restriction digestion in three compound heterozygous probands. Reverse-transcriptase PCR with allele-specific restriction digestion in patient-derived samples PloS one Medium 21738759
2013 The D50N KID-syndrome Cx26 mutation produces multiple aberrant hemichannel properties: loss of inhibition by extracellular Ca2+, decreased unitary conductance, increased open hemichannel current rectification, and voltage-shifted activation. D50 was established as a pore-lining residue; negative charge at D50 strongly influences open hemichannel properties. Evidence suggests Q48–D50 interacts to shift hemichannel voltage activation; the K61–D50 interaction proposed from the crystal structure was not detected in hemichannels. In gap junction channels, D50 substitutions caused loss of function. Electrophysiology of Cx26 hemichannels and gap junction channels with site-directed mutagenesis The Journal of general physiology High 23797419
2013 Two KID syndrome mutations, Cx26-D50A and Cx26-A88V, form active hemichannels with significantly increased membrane currents compared to wild-type Cx26 in three expression systems (Xenopus oocytes, HeLa cells, primary human keratinocytes). This increased hemichannel activity was not due to elevated protein expression, accelerated cell death in low-extracellular calcium, and was blocked by increased extracellular calcium, establishing gain-of-hemichannel-function as a shared mechanism for KID syndrome mutations. Xenopus oocyte cRNA injection, HeLa cell transfection, primary human keratinocyte transfection; electrophysiology; cell viability assay American journal of physiology. Cell physiology High 23447037
2017 Double heterozygous deletion of Cx26 and Cx30 specifically in cochlear lateral wall connective tissue cells (but not in epithelial cells of the organ of Corti) reduced endocochlear potential (EP) and caused hearing loss in mice, while sole Cx26+/- or Cx30+/- heterozygotes had normal hearing. Cx26 and Cx30 were co-expressed in the same gap junctional plaques in the cochlear lateral wall, establishing that digenic Cx26/Cx30 mutations impair heterologous coupling in the lateral wall to reduce EP. Conditional double heterozygous knockout mouse models; auditory brainstem responses; endocochlear potential measurement; immunolocalization of Cx26 and Cx30 in cochlear lateral wall Neurobiology of disease High 28823936
2017 In Gjb2+/- heterozygous mice, partial loss of Cx26 caused accelerated age-related hearing loss linked to: apoptosis and oxidative damage in the cochlear duct, reduced glutathione release from connexin hemichannels, decreased nutrient delivery via cochlear gap junctions, and dysregulation of the Nrf2 oxidative stress pathway. This establishes a redox/Nrf2 mechanism for Cx26 partial loss-of-function. Gjb2+/- mouse model; ABR and DPOAE measurements; cochlear histology; oxidative stress markers; glutathione assays; Nrf2 pathway gene expression analysis Redox biology Medium 30199819
2018 Cx26 forms a signaling complex with the pluripotency transcription factor NANOG and focal adhesion kinase (FAK) in triple-negative breast cancer stem cells (CSCs), resulting in NANOG stabilization and FAK activation. This FAK/NANOG-containing complex is not formed in normal mammary epithelial or luminal breast cancer cells. Cx26 is necessary and sufficient for CSC self-renewal maintenance. Co-immunoprecipitation, loss-of-function and gain-of-function experiments in TNBC CSCs; FAK activation assays; NANOG stability assays Nature communications Medium 29422613
2018 The syndromic deafness mutation G12R in Cx26 impairs both fast and slow hemichannel gating. Single-channel recordings showed large increase in open probability and loss of transitions to the subconductance state (fast gating). Molecular dynamics simulations indicated G12R displaces the N-terminus toward the cytoplasm, creating an interaction between R12 (N-terminus) and R99 (intracellular loop) that disrupts gating. Disruption of this R12–R99 interaction restored gating, establishing a molecular mechanism for gain-of-function hemichannel phenotype. Macroscopic and single-channel electrophysiology of Cx26 hemichannels; site-directed mutagenesis; molecular dynamics simulations The Journal of general physiology High 29643172
2018 Gjb2 conditional knockdown in mice at postnatal day 0 (but not P8) caused failure of phalangeal process development in Deiters' cells and significant reduction in microtubule (acetylated α-tubulin) formation in pillar cells, resulting in failure of the tunnel of Corti to open and severe hearing loss. This establishes a role for Cx26 in postnatal cytoskeletal development of the organ of Corti. Conditional transgenic Gjb2 knockdown at P0 and P8; ABR; cochlear histology; electron microscopy; immunostaining for acetylated α-tubulin Disease models & mechanisms Medium 29361521
2020 Elevated CO2 (55 mmHg) closes Cx26 gap junction channels via a mechanism dependent on residues K125 and R104 (the same residues required for CO2-dependent opening of Cx26 hemichannels), and this effect is independent of pH changes. Mutations K125R or R104A abolished CO2-dependent gap junction closure but not pH-dependent closure. KID syndrome mutations (N14K, A40V, A88V combined with M151L) also abolished CO2-dependent closure. Elastic network modelling indicates CO2 binding favors the closed configuration for gap junctions but the open state for hemichannels. Dye transfer assay (fluorescent glucose analogue NBDG), whole-cell patch clamp electrophysiology, site-directed mutagenesis, CO2/propionate manipulation, elastic network modelling The Journal of physiology High 33022747
2023 Homozygous Gjb2 35delG/35delG mice generated by tetraploid embryo complementation showed profound hearing loss at P14. Mechanistic analyses demonstrated that the 35delG mutation disrupts the function and formation of intercellular gap junction channels in the cochlea rather than affecting survival or function of hair cells. Advanced androgenic haploid embryonic stem cell semi-cloning technology; tetraploid embryo complementation; ABR; cochlear gap junction functional analysis Cellular and molecular life sciences : CMLS Medium 37178259
1998 Transcriptional upregulation of GJB2 (Cx26) by phorbol ester (TPA) in mammary epithelial cells is mediated through the protein kinase C (PKC) pathway. Nuclear run-on assays showed TPA increases the rate of transcriptional initiation. A TPA-induced DNase I hypersensitivity region ~1 kb upstream in intron 1 contains two TRE-like TGAT/ATCA elements and a PEA3 motif; both TRE-like elements bound AP1. CAT reporter assays confirmed TPA inducibility of this region. Nuclear run-on assay, DNase I hypersensitivity mapping, EMSA (AP1 binding), CAT reporter assay, PKC inhibitor (calphostin C) treatment Gene Medium 9524250
2014 Cx26 acts as a negative regulator of proliferation in repairing human airway epithelial basal cells. siRNA-mediated Cx26 silencing enhanced Ki67-labeling (proliferation) and decreased KLF4 transcription in immortalized cell lines. Primary HAEC lentiviral shRNA knockdown confirmed enhanced proliferation. Cx26 is expressed in a CK14-positive basal-like progenitor cell population during wound repair. siRNA knockdown in immortalized airway epithelial lines; lentiviral shRNA in primary HAECs; Ki67 and KLF4 mRNA/protein assays; wound closure assay The international journal of biochemistry & cell biology Medium 24569117
2003 Cx26 mutants R75W and ΔE42 (first extracellular loop mutations causing deafness plus skin disease) were both transported to the cell surface and assembled into gap junction-like structures in HeLa cells, but neither formed gap junctions permeable to Lucifer Yellow, establishing them as loss-of-function mutations. Endogenous Cx26 and Cx43 (but not Cx30, Cx32, or Cx37) were expressed in rat epidermal keratinocytes (REK cells). GFP-tagged Cx26 mutant expression in HeLa cells; Lucifer Yellow dye transfer assay; endogenous connexin expression in REK cells by immunostaining Cell communication & adhesion Medium 14681041

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 GJB2 mutations and degree of hearing loss: a multicenter study. American journal of human genetics 425 16380907
1989 Sequence and tissue distribution of a second protein of hepatic gap junctions, Cx26, as deduced from its cDNA. The Journal of cell biology 419 2557354
1998 Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss. American journal of human genetics 411 9529365
1999 Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling. Lancet (London, England) 335 10218527
2000 Prevalent connexin 26 gene (GJB2) mutations in Japanese. Journal of medical genetics 309 10633133
2013 GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype. The Laryngoscope 242 23900770
2003 Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. American journal of human genetics 229 14571368
1992 Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues. International journal of cancer 217 1318266
2001 Identification of cells expressing Cx43, Cx30, Cx26, Cx32 and Cx36 in gap junctions of rat brain and spinal cord. Cell communication & adhesion 180 12064610
2009 GJB2 mutation spectrum in 2,063 Chinese patients with nonsyndromic hearing impairment. Journal of translational medicine 172 19366456
1999 Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1). Pediatrics 161 10049954
2001 A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment. Journal of medical genetics 140 11483639
1999 Cx26 deafness: mutation analysis and clinical variability. Journal of medical genetics 117 10544226
2005 Mechanisms of Cx43 and Cx26 transport to the plasma membrane and gap junction regeneration. Journal of cell science 109 16159960
1999 Clinical phenotype and mutations in connexin 26 (DFNB1/GJB2), the most common cause of childhood hearing loss. American journal of medical genetics 102 10704187
2015 Ethnic-specific spectrum of GJB2 and SLC26A4 mutations: their origin and a literature review. The Annals of otology, rhinology, and laryngology 97 25999548
2007 Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. The British journal of dermatology 97 17381453
2003 Mutation spectrum of the connexin 26 (GJB2) gene in Taiwanese patients with prelingual deafness. Genetics in medicine : official journal of the American College of Medical Genetics 95 12792423
2005 In vitro and in vivo suppression of GJB2 expression by RNA interference. Human molecular genetics 94 15857852
2007 M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance. American journal of medical genetics. Part A 85 17935238
2004 Molecular epidemiology of DFNB1 deafness in France. BMC medical genetics 84 15070423
1994 A gene responsible for a dominant form of neurosensory non-syndromic deafness maps to the NSRD1 recessive deafness gene interval. Human molecular genetics 80 7881423
2017 DFNB1 Non-syndromic Hearing Impairment: Diversity of Mutations and Associated Phenotypes. Frontiers in molecular neuroscience 78 29311818
2004 Functional domain mapping and selective trans-dominant effects exhibited by Cx26 disease-causing mutations. The Journal of biological chemistry 74 14978038
2005 GJB2 mutations: passage through Iran. American journal of medical genetics. Part A 73 15666300
2008 GJB2, SLC26A4 and mitochondrial DNA A1555G mutations in prelingual deafness in Northern Chinese subjects. Acta oto-laryngologica 72 18274916
2018 Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase. Nature communications 71 29422613
2013 The D50N mutation and syndromic deafness: altered Cx26 hemichannel properties caused by effects on the pore and intersubunit interactions. The Journal of general physiology 70 23797419
2010 A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression. Clinical genetics 67 20236118
2001 Sensorineural hearing loss and the incidence of Cx26 mutations in Austria. European journal of human genetics : EJHG 66 11313763
2004 GJB2: the spectrum of deafness-causing allele variants and their phenotype. Human mutation 64 15365987
2018 Cx26 partial loss causes accelerated presbycusis by redox imbalance and dysregulation of Nfr2 pathway. Redox biology 63 30199819
2013 The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity. American journal of physiology. Cell physiology 63 23447037
2006 Pathogenetic role of the deafness-related M34T mutation of Cx26. Human molecular genetics 63 16849369
2001 Connexin 26 gene (GJB2) mutation modulates the severity of hearing loss associated with the 1555A-->G mitochondrial mutation. American journal of medical genetics 63 11746015
2002 Mutations of Cx26 gene (GJB2) for prelingual deafness in Taiwan. European journal of human genetics : EJHG 59 12111646
2017 A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall. Neurobiology of disease 56 28823936
2004 Altered gating properties of functional Cx26 mutants associated with recessive non-syndromic hearing loss. Human genetics 56 15241677
2005 Loss of function mutations of the GJB2 gene detected in patients with DFNB1-associated hearing impairment. Neurobiology of disease 50 16300957
2014 Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: insights into syndromic hearing loss. Frontiers in cellular neuroscience 49 25386120
2002 Expression and developmental regulation of gap junction connexins cx26, cx32, cx43 and cx45 in the rat midbrain-floor. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 49 12008076
2009 Statistical study of 35delG mutation of GJB2 gene: a meta-analysis of carrier frequency. International journal of audiology 48 19925344
2004 Spectrum and frequencies of mutations in the GJB2 (Cx26) gene among 156 Czech patients with pre-lingual deafness. Clinical genetics 47 15253766
2000 Functional analysis of human Cx26 mutations associated with deafness. Brain research. Brain research reviews 47 10751668
2011 The DFNB1 subtype of autosomal recessive non-syndromic hearing impairment. Frontiers in bioscience (Landmark edition) 46 21622233
2006 Expression of GJB2 and GJB6 is reduced in a novel DFNB1 allele. American journal of human genetics 45 16773579
2005 Mutation analysis of the GJB2 (connexin 26) gene in Egypt. Human mutation 45 15954104
2004 Connexin 26 (GJB2) gene-related deafness and speech intelligibility after cochlear implantation. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 44 15547423
2001 Role of cytoskeletal elements in the recruitment of Cx43-GFP and Cx26-YFP into gap junctions. Cell communication & adhesion 44 12064594
2004 Relevance of connexin deafness (DFNB1) to human evolution. American journal of human genetics 42 15079193
2011 GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss. Current genomics 39 22547955
2009 GJB2 and GJB6 gene mutations found in Indian probands with congenital hearing impairment. Journal of genetics 39 20086291
2008 A new large deletion in the DFNB1 locus causes nonsyndromic hearing loss. European journal of medical genetics 38 19101659
2006 Temporal bone imaging in GJB2 deafness. The Laryngoscope 38 17146393
2017 Hypothesis of K+-Recycling Defect Is Not a Primary Deafness Mechanism for Cx26 (GJB2) Deficiency. Frontiers in molecular neuroscience 37 28603488
2001 Meta-analysis of GJB2 mutation 35delG frequencies in Europe. Genetic testing 37 11551104
2011 Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6-D13S1854). PloS one 34 21738759
2003 Genotypic and phenotypic correlations of DFNB1-related hearing impairment in the Midwestern United States. Archives of otolaryngology--head & neck surgery 33 12925341
2019 ID2 and GJB2 promote early-stage breast cancer progression by regulating cancer stemness. Breast cancer research and treatment 32 30725231
2015 The Relationship between the p.V37I Mutation in GJB2 and Hearing Phenotypes in Chinese Individuals. PloS one 32 26061099
2007 Compound heterozygosity for dominant and recessive GJB2 mutations: effect on phenotype and review of the literature. American journal of medical genetics. Part A 32 17431919
2004 GJB2 gene mutations in cochlear implant recipients: prevalence and impact on outcome. Archives of otolaryngology--head & neck surgery 32 15148174
2019 GJB2 and GJB6 Mutations in Non-Syndromic Childhood Hearing Impairment in Ghana. Frontiers in genetics 31 31620164
2018 Developmental abnormalities in supporting cell phalangeal processes and cytoskeleton in the Gjb2 knockdown mouse model. Disease models & mechanisms 31 29361521
2003 GJB2 gene mutations causing familial hereditary deafness in Turkey. International journal of pediatric otorhinolaryngology 30 14643477
2002 Exploring the clinical and epidemiological complexity of GJB2-linked deafness. American journal of medical genetics 30 12239718
2018 Connexin 26 (GJB2) Mutations Associated with Non-Syndromic Hearing Loss (NSHL). Indian journal of pediatrics 28 29542069
2007 GJB2 and GJB6 mutations in children with congenital cytomegalovirus infection. Pediatric research 28 17426645
2004 Prevalence of the GJB2 mutations and the del(GJB6-D13S1830) mutation in Brazilian patients with deafness. Hearing research 28 15464305
2022 The protective effects of systemic dexamethasone on sensory epithelial damage and hearing loss in targeted Cx26-null mice. Cell death & disease 27 35688810
2017 Predictive Value of GJB2 Mutation Status for Hearing Outcomes of Pediatric Cochlear Implantation. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 27 28322114
2014 Cx26 regulates proliferation of repairing basal airway epithelial cells. The international journal of biochemistry & cell biology 27 24569117
2009 Molecular screening of deafness in Algeria: high genetic heterogeneity involving DFNB1 and the Usher loci, DFNB2/USH1B, DFNB12/USH1D and DFNB23/USH1F. European journal of medical genetics 27 19375528
2008 Phenotype/genotype correlations in a DFNB1 cohort with ethnical diversity. The Laryngoscope 27 18758381
2017 Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions. Journal of human genetics 26 28405014
2020 Haplotype Analysis of GJB2 Mutations: Founder Effect or Mutational Hot Spot? Genes 25 32120898
2009 Prevalence of DFNB1 mutations in Argentinean children with non-syndromic deafness. Report of a novel mutation in GJB2. International journal of pediatric otorhinolaryngology 25 20022641
2005 Functional characterization of a novel Cx26 (T55N) mutation associated to non-syndromic hearing loss. Biochemical and biophysical research communications 25 16226720
2011 Pathological hemichannels associated with human Cx26 mutations causing Keratitis-Ichthyosis-Deafness syndrome. Biochimica et biophysica acta 24 21933663
2011 Spectrum of GJB2 (Cx26) gene mutations in Iranian Azeri patients with nonsyndromic autosomal recessive hearing loss. International journal of pediatric otorhinolaryngology 24 22172221
2023 The pathogenesis of common Gjb2 mutations associated with human hereditary deafness in mice. Cellular and molecular life sciences : CMLS 23 37178259
2018 The syndromic deafness mutation G12R impairs fast and slow gating in Cx26 hemichannels. The Journal of general physiology 23 29643172
2011 Vestibular dysfunction in DFNB1 deafness. American journal of medical genetics. Part A 23 21465647
2009 GJB2 and GJB6 genes: molecular study and identification of novel GJB2 mutations in the hearing-impaired Argentinean population. Audiology & neuro-otology 22 19887791
2025 Combined AAV-mediated specific Gjb2 expression restores hearing in DFNB1 mouse models. Molecular therapy : the journal of the American Society of Gene Therapy 21 40121530
2020 GJB2 mutation spectrum in the Taiwanese population and genotype-phenotype comparisons in patients with hearing loss carrying GJB2 c.109G>A and c.235delC mutations. Hearing research 21 33288323
2010 GJB2 mutation spectrum in 209 hearing impaired individuals of predominantly Caribbean Hispanic and African descent. International journal of pediatric otorhinolaryngology 21 20381175
2003 Transport and function of cx26 mutants involved in skin and deafness disorders. Cell communication & adhesion 21 14681041
2002 Non-syndromic recessive deafness in Jordan: mapping of a new locus to chromosome 9q34.3 and prevalence of DFNB1 mutations. European journal of human genetics : EJHG 20 12080392
2016 Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing: DFNB1 or Not? Medicine 19 27057829
2008 Molecular studies in the GJB2 gene (Cx26) among a deaf population from Bogotá, Colombia: results of a screening program. International journal of pediatric otorhinolaryngology 19 19027181
2012 The association between GJB2 gene polymorphism and psoriasis: a verification study. Archives of dermatological research 18 22890607
2023 Molecular Mechanisms and Clinical Phenotypes of GJB2 Missense Variants. Biology 17 37106706
2004 GJB2 (Cx26) gene mutations in Chinese patients with congenital sensorineural deafness and a report of one novel mutation. Chinese medical journal 17 15603707
2023 Functional Consequences of Pathogenic Variants of the GJB2 Gene (Cx26) Localized in Different Cx26 Domains. Biomolecules 16 37892203
2020 Opposing modulation of Cx26 gap junctions and hemichannels by CO2. The Journal of physiology 16 33022747
2013 A novel splice-site mutation in the GJB2 gene causing mild postlingual hearing impairment. PloS one 16 24039984
2012 Prevalence of DFNB1 mutations in Slovak patients with non-syndromic hearing loss. International journal of pediatric otorhinolaryngology 16 22281373
1998 Gap junction Cx26 gene modulation by phorbol esters in benign and malignant human mammary cells. Gene 16 9524250
2000 GJB2 gene mutations in childhood deafness. Acta oto-laryngologica 15 11603757

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