GJC2

Protein-coding gene in the species Homo sapiens

GJC2

Identifiers

Aliases

GJC2, CX46.6, Cx47, GJA12, HLD2, LMPH1C, PMLDAR, SPG44, gap junction protein gamma 2, LMPHM3

External IDs

OMIM: 608803 MGI: 2153060 HomoloGene: 10715 GeneCards: GJC2

Gene location (Human)

Chr.	Chromosome 1 (human)^[1]

Band	1q42.13	Start	228,149,930 bp^[1]
Band	1q42.13	End	228,159,826 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 11 (mouse)^[2]

Band	11 B1.3\|11 37.05 cM	Start	59,066,394 bp^[2]
Band	11 B1.3\|11 37.05 cM	End	59,074,039 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

inferior ganglion of vagus nerve

subthalamic nucleus

ventral tegmental area

pons

medulla oblongata

Brodmann area 10

superior vestibular nucleus

middle frontal gyrus

Brodmann area 46

inferior olivary nucleus

Top expressed in

pontine nuclei

lateral geniculate nucleus

globus pallidus

submandibular gland

medial vestibular nucleus

ventral tegmental area

optic nerve

dorsal tegmental nucleus

cerebellar cortex

medial geniculate nucleus

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	gap junction channel activity gap junction channel activity involved in cell communication by electrical coupling
Cellular component	integral component of membrane myelin sheath cell junction plasma membrane connexin complex membrane gap junction paranode region of axon neuronal cell body perikaryon proximal neuron projection
Biological process	cell communication cell-cell signaling response to toxic substance transmembrane transport cell communication by electrical coupling regulation of protein phosphorylation brain development positive regulation of gene expression positive regulation of oligodendrocyte progenitor proliferation positive regulation of calcium ion transmembrane transport negative regulation of G1/S transition of mitotic cell cycle
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


57165


118454

Ensembl


ENSG00000198835


ENSMUSG00000043448

UniProt


Q5T442


Q8BQU6

RefSeq (mRNA)


NM_020435


NM_080454 NM_175452

RefSeq (protein)


NP_065168


NP_536702 NP_780661

Location (UCSC)

Chr 1: 228.15 – 228.16 Mb

Chr 11: 59.07 – 59.07 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

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.^[5]

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.^[5]

Clinical significance

Homozygous or compound heterozygous defects in this gene are the cause of autosomal recessive Pelizaeus-Merzbacher-like disease-1.^[5]

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

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000198835 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000043448 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "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" (PDF). J. Med. Genet. 48 (4): 251–5. doi:10.1136/jmg.2010.085563. PMID 21266381. S2CID 25183142.
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. doi:10.1523/JNEUROSCI.23-11-04549.2003. PMC 6740816. 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. doi:10.1523/JNEUROSCI.23-13-05963.2003. PMC 6741267. 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. S2CID 37200249.
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. S2CID 19215348.
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. S2CID 34789690.
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. S2CID 40070741.
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. S2CID 31979444.
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