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Gene Review

GJB1  -  gap junction protein, beta 1, 32kDa

Homo sapiens

Synonyms: CMTX, CMTX1, CX32, Connexin-32, Cx32, ...
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Disease relevance of GJB1


High impact information on GJB1


Chemical compound and disease context of GJB1


Biological context of GJB1

  • Point mutations of the connexin32 (GJB1) gene in X-linked dominant Charcot-Marie-Tooth neuropathy [11].
  • Seven of these had genetically proven CMT disease type 1A (CMT1A) due to chromosome 17p11.2-12 duplication, and one had X-linked disease (CMTX) due to a mutation in the GJB1 gene [12].
  • Novel missense mutation of the connexin32 (GJB1) gene in X-linked dominant Charcot-Marie-Tooth neuropathy [13].
  • We screened the GJB1 gene for mutations by SSCP analysis and sequencing of candidate regions, in five unrelated CMT affected individuals, members of families presenting a mode of transmission and clinical findings compatible with CMTX [14].
  • Clinical, electrophysiological and molecular genetic studies in a family with X-linked dominant Charcot-Marie-Tooth neuropathy presenting a novel mutation in GJB1 Promoter and a rare polymorphism in LITAF/SIMPLE [15].

Anatomical context of GJB1


Associations of GJB1 with chemical compounds

  • A novel isoleucine at position 127 with serine (Ile127Ser) mutation in the gap junction protein beta 1 (GJB1) gene was detected [1].
  • Six out of nine nucleotide substitutions in the Cx32 gene involved two codons encoding arginine at positions 164 and 183, suggesting that these two codons may constitute two Cx32 regions prone to mutate in the Spanish population [19].
  • Cx 43 and Cx 32 never colocalized to the same cell indicating that gap junction intercellular communication differs between basal and luminal prostatic cells [20].
  • While epithelial connexin expression was not initially altered in the developing prostates following estrogen exposure, adult prostates of neonatally estrogenized rats exhibited a marked decrease in Cx 32 staining and an increased proportion of Cx 43 expressing cells [20].
  • The transfer of Lucifer yellow across gap junctions between cells expressing wild-type Cx32, Cx43, and the corresponding Cx32-Aeq and Cx43-Aeq chimeras was reduced by nocodazole treatment and abolished by brefeldin A treatment [21].

Physical interactions of GJB1

  • The D355V mutation decreases EGR2 binding to an element within the Cx32 promoter [22].

Regulatory relationships of GJB1

  • Overall, these data indicate that Cx32 is downregulated by the ILK pathway activation in rat hepatocytes and that this is mediated via the activation and nuclear translocation of Akt [23].

Other interactions of GJB1

  • Our study shows that this factor, in synergy with EGR2, strongly activates Cx32 expression in vitro by directly binding to its promoter [18].
  • In the process of screening the above cohort of patients as well as other patients for CMT-causative mutations, we identified several previously unreported mutant alleles: two for connexin 32, three for myelin protein zero, and two for peripheral myelin protein 22 [24].
  • Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations [25].
  • Two members of this gene family, connexin43 (Cx43) and connexin32 (Cx32), are abundantly expressed in the heart and liver, respectively [26].
  • Some mutations of MPZ and Cx32 were also associated with the clinical CMT2 phenotype [27].

Analytical, diagnostic and therapeutic context of GJB1

  • The study of phenotype-genotype correlations in transgenic animal models for PMP22, MPZ and Cx32 mutations will help elucidate the underlying disease mechanisms and will provide a basis for gene therapy and/or other therapeutic approaches such as treatment with neurotrophic growth factors [28].
  • Molecular dissection of transjunctional voltage dependence in the connexin-32 and connexin-43 junctions [29].
  • Using GAP11, a rabbit polyclonal antibody against the Cx32 extracellular loop 2 (151-187), a sequence that is highly homologous in Cx43, the Cx43(dim) and Cx43(bright) cells were selected from primary limbal epithelial cultures by fluorescence-activated cell sorting and were evaluated for stem cell properties [30].
  • CMT1A and CMTX xenografts examined at 16 weeks show that the nude mouse axons within the proximal part of grafts demonstrate a significant increase in axonal area with an increase in the neurofilament and membranous organelle density compared to distal graft and distal host segments [31].
  • Immunostaining for cultured dental pulp fibroblasts (DPFs) showed that Cx32 and 43 were expressed in human DPFs, and proteins corresponding to 27 (Cx32) and 43kDa (Cx43) were identified by Western blot analysis [32].


  1. X-linked Charcot-Marie-Tooth disease: phenotypic expression of a novel mutation Ile127Ser in the GJB1 (connexin 32) gene. Vondracek, P., Seeman, P., Hermanova, M., Fajkusova, L. Muscle Nerve (2005) [Pubmed]
  2. Mutation analysis in Chariot-Marie Tooth disease type 1: point mutations in the MPZ gene and the GJB1 gene cause comparable phenotypic heterogeneity. Young, P., Grote, K., Kuhlenbäumer, G., Debus, O., Kurlemann, H., Halfter, H., Funke, H., Ringelstein, E.B., Stögbauer, F. J. Neurol. (2001) [Pubmed]
  3. Gap junction protein beta 1 (GJB1) mutations and central nervous system symptoms in X-linked Charcot-Marie-Tooth disease. Takashima, H., Nakagawa, M., Umehara, F., Hirata, K., Suehara, M., Mayumi, H., Yoshishige, K., Matsuyama, W., Saito, M., Jonosono, M., Arimura, K., Osame, M. Acta neurologica Scandinavica. (2003) [Pubmed]
  4. Charcot-Marie-Tooth disease and related hereditary polyneuropathies: molecular diagnostics determine aspects of medical management. Szigeti, K., Garcia, C.A., Lupski, J.R. Genet. Med. (2006) [Pubmed]
  5. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Bergoffen, J., Scherer, S.S., Wang, S., Scott, M.O., Bone, L.J., Paul, D.L., Chen, K., Lensch, M.W., Chance, P.F., Fischbeck, K.H. Science (1993) [Pubmed]
  6. Changes in permeability caused by connexin 32 mutations underlie X-linked Charcot-Marie-Tooth disease. Oh, S., Ri, Y., Bennett, M.V., Trexler, E.B., Verselis, V.K., Bargiello, T.A. Neuron (1997) [Pubmed]
  7. Intercellular communication via gap junctions in activated rat hepatic stellate cells. Fischer, R., Reinehr, R., Lu, T.P., Schönicke, A., Warskulat, U., Dienes, H.P., Häussinger, D. Gastroenterology (2005) [Pubmed]
  8. Immunohistochemistry of gap junctions in normal and diseased gastric mucosa of humans. Uchida, Y., Matsuda, K., Sasahara, K., Kawabata, H., Nishioka, M. Gastroenterology (1995) [Pubmed]
  9. Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells. Goldberg, G.S., Bechberger, J.F., Tajima, Y., Merritt, M., Omori, Y., Gawinowicz, M.A., Narayanan, R., Tan, Y., Sanai, Y., Yamasaki, H., Naus, C.C., Tsuda, H., Nicholson, B.J. Cancer Res. (2000) [Pubmed]
  10. Androgen-regulated Formation and Degradation of Gap Junctions in Androgen-responsive Human Prostate Cancer Cells. Mitra, S., Annamalai, L., Chakraborty, S., Johnson, K., Song, X.H., Batra, S.K., Mehta, P.P. Mol. Biol. Cell (2006) [Pubmed]
  11. Point mutations of the connexin32 (GJB1) gene in X-linked dominant Charcot-Marie-Tooth neuropathy. Ionasescu, V., Searby, C., Ionasescu, R. Hum. Mol. Genet. (1994) [Pubmed]
  12. Coexistent hereditary and inflammatory neuropathy. Ginsberg, L., Malik, O., Kenton, A.R., Sharp, D., Muddle, J.R., Davis, M.B., Winer, J.B., Orrell, R.W., King, R.H. Brain (2004) [Pubmed]
  13. Novel missense mutation of the connexin32 (GJB1) gene in X-linked dominant Charcot-Marie-Tooth neuropathy. Schiavon, F., Fracasso, C., Mostacciuolo, M.L. Hum. Mutat. (1996) [Pubmed]
  14. Three novel mutations in the gap junction beta 1 (GJB1) gene coding region identified in Charcot-Marie-Tooth patients of Greek origin: T55I, R164Q, V120E. Mutation in brief no 236. Online. Karadimas, C., Panas, M., Chronopoulou, P., Avramopoulos, D., Vassilopoulos, D. Hum. Mutat. (1999) [Pubmed]
  15. Clinical, electrophysiological and molecular genetic studies in a family with X-linked dominant Charcot-Marie-Tooth neuropathy presenting a novel mutation in GJB1 Promoter and a rare polymorphism in LITAF/SIMPLE. Beauvais, K., Furby, A., Latour, P. Neuromuscul. Disord. (2006) [Pubmed]
  16. Refined localization of human connexin32 gene locus, GJB1, to Xq13.1. Corcos, I.A., Lafrenière, R.G., Begy, C.R., Loch-Caruso, R., Willard, H.F., Glover, T.W. Genomics (1992) [Pubmed]
  17. Phenotypes of X-linked Charcot-Marie-Tooth disease and altered trafficking of mutant connexin 32 (GJB1). Matsuyama, W., Nakagawa, M., Moritoyo, T., Takashima, H., Umehara, F., Hirata, K., Suehara, M., Osame, M. J. Hum. Genet. (2001) [Pubmed]
  18. Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regulated by the transcription factor SOX10. Bondurand, N., Girard, M., Pingault, V., Lemort, N., Dubourg, O., Goossens, M. Hum. Mol. Genet. (2001) [Pubmed]
  19. Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies. Bort, S., Nelis, E., Timmerman, V., Sevilla, T., Cruz-Martínez, A., Martínez, F., Millán, J.M., Arpa, J., Vílchez, J.J., Prieto, F., Van Broeckhoven, C., Palau, F. Hum. Genet. (1997) [Pubmed]
  20. Developmental exposure to estrogens alters epithelial cell adhesion and gap junction proteins in the adult rat prostate. Habermann, H., Chang, W.Y., Birch, L., Mehta, P., Prins, G.S. Endocrinology (2001) [Pubmed]
  21. Intracellular trafficking pathways in the assembly of connexins into gap junctions. George, C.H., Kendall, J.M., Evans, W.H. J. Biol. Chem. (1999) [Pubmed]
  22. The D355V mutation decreases EGR2 binding to an element within the Cx32 promoter. Musso, M., Balestra, P., Bellone, E., Cassandrini, D., Di Maria, E., Doria, L.L., Grandis, M., Mancardi, G.L., Schenone, A., Levi, G., Ajmar, F., Mandich, P. Neurobiol. Dis. (2001) [Pubmed]
  23. Activation of the integrin-linked kinase pathway downregulates hepatic connexin32 via nuclear Akt. Plante, I., Charbonneau, M., Cyr, D.G. Carcinogenesis (2006) [Pubmed]
  24. Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and genotype-phenotype correlation. Boerkoel, C.F., Takashima, H., Garcia, C.A., Olney, R.K., Johnson, J., Berry, K., Russo, P., Kennedy, S., Teebi, A.S., Scavina, M., Williams, L.L., Mancias, P., Butler, I.J., Krajewski, K., Shy, M., Lupski, J.R. Ann. Neurol. (2002) [Pubmed]
  25. Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients. Hattori, N., Yamamoto, M., Yoshihara, T., Koike, H., Nakagawa, M., Yoshikawa, H., Ohnishi, A., Hayasaka, K., Onodera, O., Baba, M., Yasuda, H., Saito, T., Nakashima, K., Kira, J., Kaji, R., Oka, N., Sobue, G. Brain (2003) [Pubmed]
  26. The human connexin gene family of gap junction proteins: distinct chromosomal locations but similar structures. Fishman, G.I., Eddy, R.L., Shows, T.B., Rosenthal, L., Leinwand, L.A. Genomics (1991) [Pubmed]
  27. Molecular analysis in Japanese patients with Charcot-Marie-Tooth disease: DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations. Numakura, C., Lin, C., Ikegami, T., Guldberg, P., Hayasaka, K. Hum. Mutat. (2002) [Pubmed]
  28. Charcot-Marie-Tooth disease and related peripheral neuropathies. De Jonghe, P., Timmerman, V., Nelis, E., Martin, J.J., Van Broeckhoven, C. J. Peripher. Nerv. Syst. (1997) [Pubmed]
  29. Molecular dissection of transjunctional voltage dependence in the connexin-32 and connexin-43 junctions. Revilla, A., Castro, C., Barrio, L.C. Biophys. J. (1999) [Pubmed]
  30. Gap junction protein connexin 43 serves as a negative marker for a stem cell-containing population of human limbal epithelial cells. Chen, Z., Evans, W.H., Pflugfelder, S.C., Li, D.Q. Stem Cells (2006) [Pubmed]
  31. Abnormal Schwann cell-axon interactions in CMT neuropathies. The effects of mutant Schwann cells on the axonal cytoskeleton and regeneration-associated myelination. Sahenk, Z. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  32. Different expressions of connexin 43 and 32 in the fibroblasts of human dental pulp. Ibuki, N., Yamaoka, Y., Sawa, Y., Kawasaki, T., Yoshida, S. Tissue & cell. (2002) [Pubmed]
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