GJC2 explained

Gap junction gamma-2 (GJC2), also known as connexin-46.6 (Cx46.6) and connexin-47 (Cx47) and gap junction alpha-12 (GJA12), is a protein that in humans is encoded by the GJC2 gene.^[1]

Function

This gene encodes a gap junction protein. Gap junction proteins are members of a large family of homologous connexins and comprise 4 transmembrane, 2 extracellular, and 3 cytoplasmic domains. This gene plays a key role in central myelination and is involved in peripheral myelination in humans.^[1]

Clinical significance

Homozygous or compound heterozygous defects in this gene are the cause of autosomal recessive Pelizaeus-Merzbacher-like disease-1.^[1]

Heterozygous missense mutations in this same gene cause pubertal onset hereditary lymphedema.

Further reading

• Ostergaard P, Simpson MA, Brice G . Rapid identification of mutations in GJC2 in primary lymphoedema using whole exome sequencing combined with linkage analysis with delineation of the phenotype. . J. Med. Genet. . 48 . 4 . 251–5 . 2011 . 21266381 . 10.1136/jmg.2010.085563 . 25183142 . etal.
• Odermatt B, Wellershaus K, Wallraff A . Connexin 47 (Cx47)-deficient mice with enhanced green fluorescent protein reporter gene reveal predominant oligodendrocytic expression of Cx47 and display vacuolized myelin in the CNS. . J. Neurosci. . 23 . 11 . 4549–59 . 2003 . 12805295 . 6740816 . 10.1523/JNEUROSCI.23-11-04549.2003. etal.
• Menichella DM, Goodenough DA, Sirkowski E . Connexins are critical for normal myelination in the CNS. . J. Neurosci. . 23 . 13 . 5963–73 . 2003 . 12843301 . 6741267 . 10.1523/JNEUROSCI.23-13-05963.2003. etal.
• Salviati L, Trevisson E, Baldoin MC . A novel deletion in the GJA12 gene causes Pelizaeus-Merzbacher-like disease. . Neurogenetics . 8 . 1 . 57–60 . 2007 . 17031678 . 10.1007/s10048-006-0065-x . 37200249 . etal.
• Ferrell RE, Baty CJ, Kimak MA . GJC2 missense mutations cause human lymphedema. . Am. J. Hum. Genet. . 86 . 6 . 943–8 . 2010 . 20537300 . 10.1016/j.ajhg.2010.04.010 . 3032064. etal.
• Uhlenberg B, Schuelke M, Rüschendorf F . Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease. . Am. J. Hum. Genet. . 75 . 2 . 251–60 . 2004 . 15192806 . 10.1086/422763 . 1216059. etal.
• Orthmann-Murphy JL, Salsano E, Abrams CK . Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. . Brain . 132 . Pt 2 . 426–38 . 2009 . 19056803 . 10.1093/brain/awn328 . 2640216. etal.
• Wang J, Wang H, Wang Y . Two novel gap junction protein alpha 12 gene mutations in two Chinese patients with Pelizaeus-Merzbacher-like disease. . Brain Dev. . 32 . 3 . 236–43 . 2010 . 19423250 . 10.1016/j.braindev.2009.03.013 . 19215348 . etal.
• Henneke M, Combes P, Diekmann S . GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease. . Neurology . 70 . 10 . 748–54 . 2008 . 18094336 . 10.1212/01.wnl.0000284828.84464.35 . 34789690 . etal.
• Orthmann-Murphy JL, Enriquez AD, Abrams CK, Scherer SS . Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease. . Mol. Cell. Neurosci. . 34 . 4 . 629–41 . 2007 . 17344063 . 10.1016/j.mcn.2007.01.010 . 1937038.
• Ruf N, Uhlenberg B . Analysis of human alternative first exons and copy number variation of the GJA12 gene in patients with Pelizaeus-Merzbacher-like disease. . Am. J. Med. Genet. B Neuropsychiatr. Genet. . 150B . 2 . 226–32 . 2009 . 18521858 . 10.1002/ajmg.b.30792 . 40070741 .
• Wolf NI, Cundall M, Rutland P . Frameshift mutation in GJA12 leading to nystagmus, spastic ataxia and CNS dys-/demyelination. . Neurogenetics . 8 . 1 . 39–44 . 2007 . 16969684 . 10.1007/s10048-006-0062-0 . 31979444 . etal.
• Ishikawa T, Sato K, Shimazaki R . [A case of autosomal recessive hypomyelinating leukodystrophy without GJA12 mutation presenting a novel phenotype]. . Rinsho Shinkeigaku . 50 . 1 . 7–11 . 2010 . 20120347 . 10.5692/clinicalneurol.50.7. etal.

Notes and References

1. Web site: Entrez Gene: gap junction protein.