GJC2

Gap junction protein, gamma 2, 47kDa

Identifiers

GJC2 ; CX46.6; Cx47; GJA12; HLD2; LMPH1C; PMLDAR; SPG44

External IDs

OMIM: 608803 MGI: 2153060 HomoloGene: 10715 IUPHAR: 731 GeneCards: GJC2 Gene

Gene ontology
Molecular function	• gap junction channel activity
Cellular component	• connexon complex • integral component of membrane • myelin sheath
Biological process	• cell-cell signaling • response to toxic substance • transmembrane transport
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
228.15 – 228.16 Mb

Chr 11:
59.18 – 59.18 Mb

PubMed search

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.

References

1 2 3 "Entrez Gene: gap junction protein".

Ostergaard P, Simpson MA, Brice G; et al. (2011). "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. doi:10.1136/jmg.2010.085563. PMID 21266381.
Odermatt B, Wellershaus K, Wallraff A; et al. (2003). "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. PMID 12805295.
Menichella DM, Goodenough DA, Sirkowski E; et al. (2003). "Connexins are critical for normal myelination in the CNS.". J. Neurosci. 23 (13): 5963–73. PMID 12843301.
Salviati L, Trevisson E, Baldoin MC; et al. (2007). "A novel deletion in the GJA12 gene causes Pelizaeus-Merzbacher-like disease.". Neurogenetics 8 (1): 57–60. doi:10.1007/s10048-006-0065-x. PMID 17031678.
Ferrell RE, Baty CJ, Kimak MA; et al. (2010). "GJC2 missense mutations cause human lymphedema.". Am. J. Hum. Genet. 86 (6): 943–8. doi:10.1016/j.ajhg.2010.04.010. PMC 3032064. PMID 20537300.
Uhlenberg B, Schuelke M, Rüschendorf F; et al. (2004). "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. doi:10.1086/422763. PMC 1216059. PMID 15192806.
Orthmann-Murphy JL, Salsano E, Abrams CK; et al. (2009). "Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations.". Brain 132 (Pt 2): 426–38. doi:10.1093/brain/awn328. PMC 2640216. PMID 19056803.
Wang J, Wang H, Wang Y; et al. (2010). "Two novel gap junction protein alpha 12 gene mutations in two Chinese patients with Pelizaeus-Merzbacher-like disease.". Brain Dev. 32 (3): 236–43. doi:10.1016/j.braindev.2009.03.013. PMID 19423250.
Henneke M, Combes P, Diekmann S; et al. (2008). "GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease.". Neurology 70 (10): 748–54. doi:10.1212/01.wnl.0000284828.84464.35. PMID 18094336.
Orthmann-Murphy JL, Enriquez AD, Abrams CK, Scherer SS (2007). "Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease.". Mol. Cell. Neurosci. 34 (4): 629–41. doi:10.1016/j.mcn.2007.01.010. PMC 1937038. PMID 17344063.
Ruf N, Uhlenberg B (2009). "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. doi:10.1002/ajmg.b.30792. PMID 18521858.
Wolf NI, Cundall M, Rutland P; et al. (2007). "Frameshift mutation in GJA12 leading to nystagmus, spastic ataxia and CNS dys-/demyelination.". Neurogenetics 8 (1): 39–44. doi:10.1007/s10048-006-0062-0. PMID 16969684.
Ishikawa T, Sato K, Shimazaki R; et al. (2010). "[A case of autosomal recessive hypomyelinating leukodystrophy without GJA12 mutation presenting a novel phenotype].". Rinsho Shinkeigaku 50 (1): 7–11. doi:10.5692/clinicalneurol.50.7. PMID 20120347.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

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GJC2

Function

Clinical significance

References

Further reading