Affinage

GJB6

Gap junction beta-6 protein · UniProt O95452

Length
261 aa
Mass
30.4 kDa
Annotated
2026-06-10
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GJB6 encodes Connexin 30 (Cx30), a gap junction protein central to cochlear ion homeostasis and to astroglial regulation of neuronal activity (PMID:12490528, PMID:30794327). In the cochlea, Cx30 is required to generate the endocochlear potential, and its loss in mice abolishes the potential and causes apoptotic degeneration of the sensory epithelium (PMID:12490528). Cx30 co-localizes and physically oligomerizes with Cx26 in shared gap junction plaques of the cochlear lateral wall, forming heteromeric connexons; deafness-associated Cx26 mutants exert dominant-negative effects on Cx30 channel function, and combined Cx26/Cx30 haploinsufficiency in the lateral wall reduces the endocochlear potential without hair cell loss (PMID:14681039, PMID:28823936). Beyond direct coding mutations, large genomic deletions spanning the GJB6 locus cause DFNB1 deafness chiefly by removing a distant cis-regulatory element that controls GJB2 expression in cis—the GJB2 allele in cis with the deletion is silenced while the trans allele remains expressed—rather than acting solely through a digenic mechanism (PMID:19723508, PMID:21738759, PMID:20236118). Cx30 traffics through the canonical ER-Golgi pathway in a Sar1-dependent manner and is an unusually long-lived membrane connexin, with plaques rebuilt from their outer edges (PMID:26359304). Disease-causing Cx30 missense mutations act through mutation-specific cellular pathologies: ER retention with apoptosis (V37E), Golgi retention with channel loss-of-function (G59R), or ER-independent apoptosis (A88V), each accompanied by selective trans-dominant effects on co-expressed connexins (PMID:24522190). In the brain, astroglial Cx30 channel activity—independent of gap-junction biochemical coupling—controls glutamate clearance and neuronal network bursting, restricts adult hippocampal neurogenesis, and regulates cerebrovascular γ-sarcoglycan expression (PMID:25698924, PMID:23618652, PMID:30794327).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 High

    Established that Cx30 is functionally required in the cochlea, answering whether GJB6 loss has a defined auditory phenotype and identifying the endocochlear potential as the affected output.

    Evidence Cx30 knockout mouse with endocochlear potential recording, audiometry, and histology of cochlear degeneration

    PMID:12490528

    Open questions at the time
    • Does not define the molecular cause of the EP deficit (ion transport vs. coupling)
    • Does not distinguish channel function from structural roles
  2. 2003 High

    Showed that Cx30 forms heteromeric connexons with Cx26 in native cochlear tissue and that Cx26 disease mutants can poison Cx30 channels, explaining how mutations in one connexin compromise the other.

    Evidence Reciprocal Co-IP from cochlear membranes, immunogold localization, and dye-transfer assays in transfected cells

    PMID:14681039

    Open questions at the time
    • Stoichiometry of heteromeric connexons not resolved
    • Does not establish in vivo functional consequence of heteromerization
  3. 2006 Medium

    Provided first evidence that a non-coding DFNB1 lesion can co-suppress GJB2 and GJB6 in cis, raising the possibility of shared cis-regulation rather than purely coding-mutation deafness.

    Evidence Allele-specific expression assay in a large deafness kindred

    PMID:16773579

    Open questions at the time
    • Regulatory element not localized
    • Single family
  4. 2009 High

    Demonstrated that the common del(GJB6-D13S1830) deletion silences GJB2 specifically in cis, redefining the disease mechanism from digenic inheritance to loss of a cis-regulatory element.

    Evidence Allele-specific RT-PCR/restriction analysis in three independent compound heterozygotes

    PMID:19723508

    Open questions at the time
    • Identity and sequence of the regulatory element not defined
    • Tissue panel limited to buccal epithelium
  5. 2010 Medium

    Mapped a candidate distant cis-regulatory region by identifying a 131-kb deletion >100 kb upstream that suppresses both GJB2 and GJB6, supporting co-regulation from a remote element.

    Evidence Array CGH breakpoint mapping and segregation analysis in a large family

    PMID:20236118

    Open questions at the time
    • Element not functionally validated as an enhancer
    • Single family
  6. 2011 High

    Narrowed the location of the shared cis-regulatory element by showing the smaller del(GJB6-D13S1854) deletion also suppresses GJB2 in cis with residual expression.

    Evidence Allele-specific expression analysis in three compound heterozygous probands

    PMID:21738759

    Open questions at the time
    • Minimal residual expression not mechanistically explained
    • Element still not directly identified
  7. 2014 High

    Resolved why different GJB6 missense mutations cause different diseases by showing each follows a distinct cellular pathology—ER retention/apoptosis, Golgi retention/loss-of-function, or ER-independent apoptosis.

    Evidence Transfected-cell expression with localization, GJIC, apoptosis, and dominant-negative co-expression assays

    PMID:24522190

    Open questions at the time
    • Cellular assays not validated in native epithelial or cochlear context
    • Mechanism of ER-independent apoptosis unresolved
  8. 2015 High

    Characterized Cx30 membrane trafficking and turnover, establishing it as an ER-Golgi-routed, unusually long-lived connexin with edge-directed plaque renewal.

    Evidence FRAP, brefeldin A/cycloheximide treatment, dominant-negative Sar1, and Cx43 co-expression imaging

    PMID:26359304

    Open questions at the time
    • Molecular basis of the long half-life not identified
    • Turnover not measured in cochlear/astroglial tissue
  9. 2015 Medium

    Showed astroglial Cx30 channel activity, not coupling, controls a specific cerebrovascular target (γ-sarcoglycan), distinguishing channel from gap-junction functions in brain.

    Evidence Cx30 KO and channel-dead T5M knock-in mice with RNA-seq and immunofluorescence of cerebrovascular fraction

    PMID:25698924

    Open questions at the time
    • Mechanism linking Cx30 channels to Sgcg regulation unknown
    • Functional consequence of Sgcg upregulation not tested
  10. 2017 High

    Localized the digenic EP defect to the cochlear lateral wall, showing combined Cx26/Cx30 haploinsufficiency there lowers the endocochlear potential without hair cell degeneration.

    Evidence Conditional and conventional double heterozygous knockouts with ABR, EP recordings, and co-localization

    PMID:28823936

    Open questions at the time
    • Quantitative contribution of heteromeric vs homomeric channels not resolved
    • Does not address human digenic genotypes directly
  11. 2019 Medium

    Linked astroglial Cx30 to neuronal network excitability by showing it controls glutamate clearance and seizure severity independently of biochemical coupling.

    Evidence Cx30 KO mice with in vivo kainate seizure model, ex vivo electrophysiology, and glutamate clearance assays

    PMID:30794327

    Open questions at the time
    • Molecular pathway from Cx30 channels to glutamate transport unknown
    • Single lab
  12. 2022 Medium

    Mapped GJB6 and GJB2 transcript distributions in the human cochlea, revealing GJB6-dominant expression and partially distinct cell populations consistent with separate gap junction plaques.

    Evidence RNAscope in situ hybridization with confocal and super-resolution imaging on human cochlear sections

    PMID:36204137

    Open questions at the time
    • mRNA distribution does not establish protein-level channel composition
    • Functional permeability differences inferred, not measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise identity, sequence, and bound trans-acting factors of the distant cis-regulatory element co-controlling GJB2 and GJB6 remain undefined, as does the molecular basis of channel-independent astroglial Cx30 signaling.
  • Regulatory element not cloned or functionally reconstituted
  • Mechanism coupling Cx30 channels to glutamate clearance and gene regulation unresolved
  • Structural basis of mutation-specific trafficking defects unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2
Partners
GJA1GJB2
Complex memberships
Cx26/Cx30 heteromeric connexongap junction plaque

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Cx30 (GJB6) knockout mice lack the endocochlear potential from the onset of hearing, and after postnatal day 18 exhibit cochlear sensory epithelium degeneration by apoptosis, demonstrating that Cx30 is required for generating the endocochlear potential and for survival of auditory hair cells. Knockout mouse model (deletion of Cx30 coding region), electrophysiological measurement of endocochlear potential, histological analysis of cochlear degeneration Human molecular genetics High 12490528
2003 Cx26 and Cx30 co-localize in the same gap junction plaques in cochlear tissues and can oligomerize to form heteromeric connexons. Immunoprecipitation of cochlear membrane proteins with either Cx30 or Cx26 antibodies co-precipitates both proteins. Deafness-associated Cx26 mutants (W44S, G59A, R75W) exert a dominant-negative effect on Cx30 channel function, reducing neurobiotin transfer in co-expressing cells. Co-immunoprecipitation from cochlear membranes, transfected HeLa cell functional assays (dye transfer), immunogold labeling of cochlear thin sections, dual dye injection into cochlear supporting cells Cell communication & adhesion High 14681039
2009 The del(GJB6-D13S1830) deletion causes allele-specific loss of GJB2 mRNA expression in cis (not a digenic mechanism): in compound heterozygotes, the GJB2 allele in cis with the deletion is not expressed, while the GJB2 allele in trans is expressed. This demonstrates the deletion removes a cis-regulatory element required for GJB2 expression. Allele-specific expression analysis by reverse-transcriptase PCR and restriction digestion from buccal epithelium RNA in three unrelated compound heterozygous individuals Biochemical and biophysical research communications High 19723508
2011 The smaller del(GJB6-D13S1854) deletion similarly causes allele-specific reduction of GJB2 mRNA expression in cis, though minimal residual GJB2 expression from the deletion allele remains. This narrows the location of the putative cis-regulatory element shared with del(GJB6-D13S1830). Allele-specific expression analysis by RT-PCR and restriction digestion in three compound heterozygous probands PloS one High 21738759
2006 A novel DFNB1 allele (not encompassing GJB6 coding sequence) dramatically reduces expression of both GJB2 and GJB6 mRNA from the same chromosome, providing the first evidence of a deafness-associated regulatory mutation affecting GJB2 and suggesting co-regulation of GJB2 and GJB6. PCR-based qualitative allele-specific expression assay in a large kindred segregating deafness with the 35delG allele in trans American journal of human genetics Medium 16773579
2010 A novel 131.4-kb deletion whose proximal breakpoint lies more than 100 kb upstream of the GJB2 and GJB6 transcriptional start sites segregates as a completely penetrant DFNB1 allele and reduces expression of both GJB2 and GJB6 mRNA, supporting the existence of a distant cis-regulatory region controlling both genes. Array comparative genomic hybridization, segregation analysis in a large family, allele-specific expression previously demonstrated in the same individuals Clinical genetics Medium 20236118
2017 Double heterozygous deletion of Cx26 and Cx30 (Cx26+/-/Cx30+/-) in cochlear lateral wall cells (but not in epithelial cells of the organ of Corti) reduces the endocochlear potential and causes hearing loss in mice, without hair cell degeneration. Most Cx26 and Cx30 in the cochlear lateral wall co-localize in the same gap junction plaques, indicating that digenic Cx26/Cx30 mutations impair heterozygous coupling specifically in the lateral wall to reduce the endocochlear potential. Double heterozygous knockout mouse models (conditional and conventional), auditory brainstem response measurements, endocochlear potential recordings, immunofluorescence co-localization Neurobiology of disease High 28823936
2014 Four disease-associated Cx30 mutants cause distinct cellular pathologies: T5M (non-syndromic hearing loss) forms functional gap junction channels and hemichannels similar to wild-type; V37E (Clouston/KID syndrome) is retained in the ER and induces apoptosis; G59R (Vohwinkel/Bart-Pumphrey syndrome) is retained in the Golgi and loses gap junction and hemichannel function without causing cell death; A88V (Clouston syndrome) induces apoptosis via an ER-independent mechanism. All mutants also exhibit selective trans-dominant effects on co-expressed connexins. Transfected cell expression of mutant Cx30 constructs, fluorescence microscopy (ER/Golgi co-localization), functional GJIC assays, apoptosis assays, dominant-negative co-expression experiments Journal of cell science High 24522190
2015 Cx30 is an unusually long-lived connexin (half-life >12 h at the membrane) that is insensitive to prolonged brefeldin A or cycloheximide treatment. Cx30 gap junction plaques are rebuilt from the outer edges with older channels residing in the inner core. Cx30 traffics via the ER-Golgi pathway (dominant-negative Sar1 GTPase accumulates Cx30 in the ER). When co-expressed with Cx43, Cx30 segregates into distinct domains within common gap junction plaques. Fluorescence recovery after photobleaching (FRAP), pharmacological inhibition (brefeldin A, cycloheximide), dominant-negative Sar1 GTPase expression, co-expression with Cx43 and fluorescence microscopy Journal of cell science High 26359304
2015 Astroglial Cx30 channel function (not just gap-junction coupling) specifically regulates expression of γ-Sarcoglycan (Sgcg) in the cerebrovascular fraction; Cx30 knockout and a channel-closed Cx30 point mutant (T5M) both upregulate Sgcg, while other sarcoglycan complex members are unaffected. Cx30 knockout mouse model (Cx30Δ/Δ) and Cx30 T5M knock-in mouse model, cerebrovascular fraction isolation, gene expression analysis (RNA-seq), immunofluorescence Frontiers in cellular neuroscience Medium 25698924
2013 Knockout of Cx30 in mice significantly enhances survival of newborn neurons in the adult hippocampal subgranular zone without affecting their proliferation rate (tendency toward increased proliferation) or neuronal differentiation, demonstrating a Cx30-specific role in restricting adult hippocampal neurogenesis. Conventional Cx30 knockout mouse, Ki67 immunoreactivity (proliferation), BrdU incorporation and survival assay, immunofluorescent co-localization with DCX and NeuN (differentiation) Neuroscience letters Medium 23618652
2019 Astroglial Cx30 regulates neuronal population bursts and kainate-induced seizure severity through control of astroglial glutamate clearance, independently of gap-junction-mediated biochemical coupling. Cx30 knockout mice, in vivo kainate seizure model with behavioral scoring, ex vivo electrophysiology, glutamate clearance assays Glia Medium 30794327
2005 The human GJB6 gene has six exons with tissue-specific alternative splicing; a basal promoter active in keratinocytes responds to EGF receptor activation. A non-coding exon present in brain Cx30 cDNA is absent from keratinocyte cDNA, indicating tissue-specific splicing of GJB6. Genomic sequencing/cloning, RT-PCR from multiple tissues, promoter-reporter assay in keratinocyte cell line with EGF receptor activation Gene Medium 15792634
2012 The transcription factor ΔNp63α directly upregulates GJB6 expression and binds to sequences in intron 1 of GJB6 in vitro. Cx30 expression in skin overlaps with p63 expression in hair follicles, nails, and palmoplantar epidermis. In vitro overexpression of ΔNp63α isoform in cultured cells with GJB6 expression measurement, in vitro binding assays to intron 1 sequences, immunostaining of human skin and mouse embryos Journal of dermatological science Medium 23219093
2006 In the adult mouse mammary gland, Cx26 and Cx30 co-localize in junctional plaques between epithelial cells during late pregnancy and early lactation, forming hemichannels of mixed connexin content. Cx26/Cx30 heteromeric channels are insensitive to closure by physiological taurine concentrations, unlike Cx26/Cx32 channels. Oligonucleotide microarray, immunofluorescence co-localization, functional channel assay with taurine in heteromeric connexin-expressing cells Cell and tissue research Medium 17120054
2005 The del(GJB6-D13S1830) deletion causes cell-type-specific loss of Cx26 (GJB2) protein expression in ductal sweat gland epithelium (but not other skin cell types), consistent with the deletion removing a cis-regulatory element for GJB2 in this specific cell type. Immunohistochemistry on patient skin biopsies, bioinformatic analysis of the deleted region Clinical and experimental dermatology Medium 16197390
2004 A heterozygous GJB6 missense mutation (V37E), predicted to alter the first transmembrane helix of Cx30, was identified in a patient with KID syndrome-like phenotype and atrichia in the absence of any GJB2 mutation, establishing that GJB6 mutations can cause KID syndrome-type disease distinct from Clouston syndrome. Mutation screening of GJB6 coding sequence by sequencing in a patient with clinical KID syndrome features; GJB2 excluded by sequencing The Journal of investigative dermatology Low 15140211
2022 In the human cochlea, GJB6 mRNA transcripts are more abundant than GJB2 transcripts overall; GJB6 (but not GJB2) transcripts are present in intermediate cells of the stria vascularis; GJB2 and GJB6 transcripts are detected in the same cells (outer sulcus, spiral ligament, stria vascularis) but also in separate cell populations, consistent with distinct gap junction plaques of differing permeability. RNAscope in situ hybridization on archival human cochlear sections, confocal and super-resolution structured illumination microscopy Frontiers in molecular neuroscience Medium 36204137
2009 A novel p.Gly59Arg mutation in the first extracellular loop of Cx30 (GJB6) causes palmoplantar keratoderma with pseudoainhum, knuckle pads, and severe sensorineural hearing loss (overlapping with phenotypes of comparable Cx26 Gly59 mutations), supporting heteromeric Cx26/Cx30 channel formation in vivo and a dominant mechanism of the mutation. Sequencing of GJB6 in a patient; electron microscopy of lesional epidermis; GJB2 excluded by sequencing The British journal of dermatology Low 19416251

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1985 The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 1791 3882559
2003 Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential. Human molecular genetics 287 12490528
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
2016 EDH: endothelium-dependent hyperpolarization and microvascular signalling. Acta physiologica (Oxford, England) 186 26752699
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
2003 Coupling of astrocyte connexins Cx26, Cx30, Cx43 to oligodendrocyte Cx29, Cx32, Cx47: Implications from normal and connexin32 knockout mice. Glia 167 14603462
2001 A deletion mutation in GJB6 cooperating with a GJB2 mutation in trans in non-syndromic deafness: A novel founder mutation in Ashkenazi Jews. Human mutation 156 11668644
1996 CNS microvascular pericytes express macrophage-like function, cell surface integrin alpha M, and macrophage marker ED-2. Microvascular research 139 8901442
2002 A large deletion including most of GJB6 in recessive non syndromic deafness: a digenic effect? European journal of human genetics : EJHG 133 11896458
2003 Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands. Genetics in medicine : official journal of the American College of Medical Genetics 132 12865758
1997 ED2+ macrophages increase selectively myoblast proliferation in muscle cultures. Biochemical and biophysical research communications 113 9207234
1990 Characterization and expression of the antigen present on resident rat macrophages recognized by monoclonal antibody ED2. Immunobiology 112 2098324
2003 Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations. The Journal of investigative dermatology 94 12648223
2007 A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. Genetics in medicine : official journal of the American College of Medical Genetics 93 17666888
1989 Splenic outer periarterial lymphoid sheath (PALS): an immunoproliferative microenvironment constituted by antigen-laden marginal metallophils and ED2-positive macrophages in the rat. Cell and tissue research 88 2790931
2004 Genetic heterogeneity of KID syndrome: identification of a Cx30 gene (GJB6) mutation in a patient with KID syndrome and congenital atrichia. The Journal of investigative dermatology 84 15140211
2005 GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients. Archives of otolaryngology--head & neck surgery 76 15967879
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
2018 Endothelium-Dependent Hyperpolarization (EDH) in Hypertension: The Role of Endothelial Ion Channels. International journal of molecular sciences 65 29361737
2009 Cx30.2 enhancer analysis identifies Gata4 as a novel regulator of atrioventricular delay. Development (Cambridge, England) 62 19592579
2003 The inner ear contains heteromeric channels composed of cx26 and cx30 and deafness-related mutations in cx26 have a dominant negative effect on cx30. Cell communication & adhesion 61 14681039
2008 Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients. International journal of pediatric otorhinolaryngology 57 18585793
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
1996 Differential expression of four connexin genes, Cx-26, Cx-30.3, Cx-32, and Cx-43, in the porcine ovarian follicle. Endocrinology 55 8895378
2009 Prevalence of GJB2 (connexin-26) and GJB6 (connexin-30) mutations in a cohort of 300 Brazilian hearing-impaired individuals: implications for diagnosis and genetic counseling. Ear and hearing 53 19125024
2009 The digenic hypothesis unraveled: the GJB6 del(GJB6-D13S1830) mutation causes allele-specific loss of GJB2 expression in cis. Biochemical and biophysical research communications 51 19723508
2007 Mutations in GJB2, GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment. American journal of medical genetics. Part A 48 17357124
2011 Absence of GJB2 gene mutations, the GJB6 deletion (GJB6-D13S1830) and four common mitochondrial mutations in nonsyndromic genetic hearing loss in a South African population. International journal of pediatric otorhinolaryngology 45 21392827
2006 Expression of GJB2 and GJB6 is reduced in a novel DFNB1 allele. American journal of human genetics 45 16773579
2014 Mutations in Cx30 that are linked to skin disease and non-syndromic hearing loss exhibit several distinct cellular pathologies. Journal of cell science 43 24522190
2015 The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels. Frontiers in cellular neuroscience 42 25698924
1999 Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13q12. Genomics 40 10610709
2013 Astrocytic Cx43 and Cx30 differentially modulate adult neurogenesis in mice. Neuroscience letters 39 23618652
2009 GJB2 and GJB6 gene mutations found in Indian probands with congenital hearing impairment. Journal of genetics 39 20086291
1990 Glycosyl receptors in macrophage subpopulations of rat spleen and lymph node. A comparative study using neoglycoproteins and monoclonal antibodies ED1, ED2 and ED3. Cell and tissue research 39 2257613
2004 Large deletion of the GJB6 gene in deaf patients heterozygous for the GJB2 gene mutation: genotypic and phenotypic analysis. American journal of medical genetics. Part A 37 15150777
2005 Prevalence of GJB2 mutations and the del(GJB6-D13S1830) in Argentinean non-syndromic deaf patients. Hearing research 35 15964725
2020 Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer's Disease. Frontiers in neuroscience 34 33117125
2011 Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6-D13S1854). PloS one 34 21738759
2009 Hearing loss features in GJB2 biallelic mutations and GJB2/GJB6 digenic inheritance in a large Italian cohort. International journal of audiology 34 19173109
1996 ED2-positive perivascular cells act as neuronophages during delayed neuronal loss in the facial nucleus of the rat. Glia 34 8929900
2003 Differences in expression patterns between mouse connexin-30.2 (Cx30.2) and its putative human orthologue, connexin-31.9. FEBS letters 32 12681499
2019 GJB2 and GJB6 Mutations in Non-Syndromic Childhood Hearing Impairment in Ghana. Frontiers in genetics 31 31620164
2014 In search of genetic markers for nonsyndromic deafness in Africa: a study in Cameroonians and Black South Africans with the GJB6 and GJA1 candidate genes. Omics : a journal of integrative biology 31 24785695
2005 Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutations. International journal of pediatric otorhinolaryngology 31 15656949
2003 Use of a multiplex PCR/sequencing strategy to detect both connexin 30 (GJB6) 342 kb deletion and connexin 26 (GJB2) mutations in cases of childhood deafness. American journal of medical genetics. Part A 31 12910486
2005 Double heterozygosity with mutations involving both the GJB2 and GJB6 genes is a possible, but very rare, cause of congenital deafness in the Czech population. Annals of human genetics 29 15638823
2005 Autosomal recessive and sporadic deafness in Morocco: high frequency of the 35delG GJB2 mutation and absence of the 342-kb GJB6 variant. Hearing research 29 16243461
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
2003 The 342-kb deletion in GJB6 is not present in patients with non-syndromic hearing loss from Austria. Human mutation 28 12872268
2005 Ethnicity and mutations in GJB2 (connexin 26) and GJB6 (connexin 30) in a multi-cultural Canadian paediatric Cochlear Implant Program. International journal of pediatric otorhinolaryngology 27 16125251
2005 Specific loss of connexin 26 expression in ductal sweat gland epithelium associated with the deletion mutation del(GJB6-D13S1830). Clinical and experimental dermatology 27 16197390
2021 Beneficial effect of capsaicin via TRPV4/EDH signals on mesenteric arterioles of normal and colitis mice. Journal of advanced research 26 35777913
2015 Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats. Pharmacology research & perspectives 26 26171229
2015 Spectrum and frequency of GJB2, GJB6 and SLC26A4 gene mutations among nonsyndromic hearing loss patients in eastern part of India. Gene 26 26188157
2007 Common mutation analysis of GJB2 and GJB6 genes in affected families with autosomal recessive non-syndromic hearing loss from Iran: simultaneous detection of two common mutations (35delG/del(GJB6-D13S1830)) in the DFNB1-related deafness. International journal of pediatric otorhinolaryngology 26 17368814
2017 CYP epoxygenase-derived H2O2 is involved in the endothelium-derived hyperpolarization (EDH) and relaxation of intrarenal arteries. Free radical biology & medicine 25 28212823
2011 GJB2 and GJB6 genes and the A1555G mitochondrial mutation are only minor causes of nonsyndromic hearing loss in the Qatari population. International journal of audiology 25 22103400
2009 Low incidence of GJB2, GJB6 and mitochondrial DNA mutations in North Indian patients with non-syndromic hearing impairment. Biochemical and biophysical research communications 25 19465004
2009 Analysis of the GJB2 and GJB6 genes in Italian patients with nonsyndromic hearing loss: frequencies, novel mutations, genotypes, and degree of hearing loss. Genetic testing and molecular biomarkers 24 19371219
2004 Phenotypic variability of non-syndromic hearing loss in patients heterozygous for both c.35delG of GJB2 and the 342-kb deletion involving GJB6. Hearing research 24 14759569
2019 GJB2 and GJB6 Mutations in Hereditary Recessive Non-Syndromic Hearing Impairment in Cameroon. Genes 23 31731535
2013 Upregulation of heme oxygenase-1 potentiates EDH-type relaxations in the mesenteric artery of the spontaneously hypertensive rat. American journal of physiology. Heart and circulatory physiology 23 24014672
2008 Cx30.2 can form heteromeric gap junction channels with other cardiac connexins. Biochemical and biophysical research communications 23 18291099
2006 Nature of Cx30-containing channels in the adult mouse mammary gland. Cell and tissue research 23 17120054
2019 Comparison of Predictive In Silico Tools on Missense Variants in GJB2, GJB6, and GJB3 Genes Associated with Autosomal Recessive Deafness 1A (DFNB1A). TheScientificWorldJournal 22 31015822
2009 GJB2 and GJB6 genes: molecular study and identification of novel GJB2 mutations in the hearing-impaired Argentinean population. Audiology & neuro-otology 22 19887791
2004 Screening for monogenetic del(GJB6-D13S1830) and digenic del(GJB6-D13S1830)/GJB2 patterns of inheritance in deaf individuals from Eastern Austria. Hearing research 22 15464308
2017 Myoendothelial coupling through Cx40 contributes to EDH-induced vasodilation in murine renal arteries: evidence from experiments and modelling. Acta physiologica (Oxford, England) 21 28613412
2009 Endothelium-dependent vasodilation in myogenically active mouse skeletal muscle arterioles: role of EDH and K(+) channels. Microcirculation (New York, N.Y. : 1994) 21 19424929
2016 Reactive oxygen species facilitate the EDH response in arterioles by potentiating intracellular endothelial Ca(2+) release. Free radical biology & medicine 20 27320188
2015 Cx30 exhibits unique characteristics including a long half-life when assembled into gap junctions. Journal of cell science 20 26359304
2006 High frequency of 35delG GJB2 mutation and absence of del(GJB6-D13S1830) in Greek Cypriot patients with nonsyndromic hearing loss. Genetic testing 20 17253936
2005 Gene structure and promoter analysis of the human GJB6 gene encoding connexin 30. Gene 20 15792634
2007 Detection of the 35delG/GJB2 and del(GJB6-D13S1830) mutations in Venezuelan patients with autosomal recessive nonsyndromic hearing loss. Genetic testing 18 18294049
2012 Evaluation of the pathogenicity of GJB3 and GJB6 variants associated with nonsyndromic hearing loss. Biochimica et biophysica acta 16 22617145
2012 GJB6, of which mutations underlie Clouston syndrome, is a potential direct target gene of p63. Journal of dermatological science 16 23219093
2004 The frequency of GJB2 and GJB6 mutations in the New York State newborn population: feasibility of genetic screening for hearing defects. Clinical genetics 16 15025729
2004 Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations. Molecular aspects of medicine 16 15051326
2019 Astroglial Cx30 sustains neuronal population bursts independently of gap-junction mediated biochemical coupling. Glia 15 30794327
2010 Prevalence of 35delG/GJB2 and del (GJB6-D13S1830) mutations in patients with non-syndromic deafness from a population of Espírito Santo-Brazil. Brazilian journal of otorhinolaryngology 15 20835527
2020 Tight Junction-Related CLDN5 and CLDN6 Genes, and Gap Junction-Related GJB6 and GJB7 Genes Are Somatically Mutated in Gastric and Colorectal Cancers. Pathology oncology research : POR 14 32170581
2020 GJB2 and GJB6 Genetic Variant Curation in an Argentinean Non-Syndromic Hearing-Impaired Cohort. Genes 14 33096615
2015 Stochastic model of endothelial TRPV4 calcium sparklets: effect of bursting and cooperativity on EDH. Biophysical journal 14 25809269
2022 GJB2 and GJB6 gene transcripts in the human cochlea: A study using RNAscope, confocal, and super-resolution structured illumination microscopy. Frontiers in molecular neuroscience 13 36204137
2009 Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss. The British journal of dermatology 13 19416251
2008 Mutation analysis of the Cx26, Cx30, and Cx31 genes in autosomal recessive nonsyndromic hearing impairment. Acta oto-laryngologica 13 18607988
2017 The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric arteries. Vascular pharmacology 12 29038048
2015 Novel mutations in GJB6 and GJB2 in Clouston syndrome. Clinical and experimental dermatology 12 25808784
2015 Prevalence of Deafness-Associated Connexin-26 (GJB2) and Connexin-30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily. Annals of human genetics 12 26096904
2015 Mice with conditional deletion of Cx26 exhibit no vestibular phenotype despite secondary loss of Cx30 in the vestibular end organs. Hearing research 12 26232528
2014 GJB2 and GJB6 mutations are an infrequent cause of autosomal-recessive nonsyndromic hearing loss in residents of Mexico. International journal of pediatric otorhinolaryngology 12 25288386
2010 Mutation analysis of GJB2 and GJB6 genes in Southeastern Brazilians with hereditary nonsyndromic deafness. Molecular biology reports 12 20563649
2008 Absence of GJB3 and GJB6 mutations in Moroccan familial and sporadic patients with autosomal recessive non-syndromic deafness. International journal of pediatric otorhinolaryngology 12 18809214
2003 p27 and cyclin E/D2 associations in testicular germ cell tumors: implications for tumorigenesis. Applied immunohistochemistry & molecular morphology : AIMM 12 12777997
2016 A known mutation in GJB6 in a large Chinese family with hidrotic ectodermal dysplasia. Journal of the European Academy of Dermatology and Venereology : JEADV 11 27137747
2014 Frequency of GJB2 and del(GJB6-D13S1830) mutations among an Ecuadorian mestizo population. International journal of pediatric otorhinolaryngology 11 25085072
2009 Flow cytometric isolation and phenotypic characterization of two subsets of ED2(+) (CD163) hepatic macrophages in rats. Hepatology research : the official journal of the Japan Society of Hepatology 11 19624775
2020 Analyses of del(GJB6-D13S1830) and del(GJB6-D13S1834) deletions in a large cohort with hearing loss: Caveats to interpretation of molecular test results in multiplex families. Molecular genetics & genomic medicine 10 32067424

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