GJC2 (Gap Junction Protein Gamma 2)
Key regulator of intercellular communication in oligodendrocytes and Schwann cells; mutations linked to CNS and PNS demyelinating disorders
Gene Information Card
| Symbol | GJC2 |
|---|---|
| Full Name | Gap Junction Protein Gamma 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.13 |
| NCBI Gene ID | 57165 ncbi.nlm.nih.gov/gene/57165 |
| Ensembl ID | ENSG00000198835 |
| UniProt ID | O75712 |
| OMIM ID | 608803 |
| HGNC ID | 17494 |
| Aliases | CX47, GJA12, GJA12P, connexin 47 |
Description
GJC2 encodes connexin 47 (Cx47), a member of the connexin family that forms gap junction channels. These channels mediate direct intercellular transfer of ions and small molecules. Cx47 is predominantly expressed in oligodendrocytes and Schwann cells, where it is essential for myelination and maintenance of the central and peripheral nervous systems. Mutations in GJC2 cause Pelizaeus-Merzbacher-like disease (PMLD) and hereditary spastic paraplegia type 44 (SPG44).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pelizaeus-Merzbacher-like disease (PMLD) | Loss of gap junction function in oligodendrocytes leads to impaired myelination and white matter degeneration. | ClinVar, OMIM |
| Hereditary spastic paraplegia 44 (SPG44) | Dominant-negative or loss-of-function mutations disrupt Cx47 hemichannel or gap junction activity, causing axonal degeneration. | ClinVar, OMIM |
| Lymphedema (rare association) | Altered Cx47 function may affect lymphatic vessel development; limited evidence. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 8.3 | Low |
| Heart | 0.6 | Not detected |
| Liver | 0.2 | Not detected |
| Kidney | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Oligodendrocytes (primary) | 15.2 | High expression; key for myelination |
| Schwann cells (primary) | 10.1 | Moderate expression; peripheral myelination |
| SH-SY5Y (neuroblastoma) | 0.5 | Low expression |
| HEK293 | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.35G>A (p.Gly12Asp) | Missense | Rare (PMLD) | Loss of gap junction function; impaired trafficking |
| c.406C>T (p.Arg136Trp) | Missense | Rare (SPG44) | Dominant-negative effect; reduced channel conductance |
| c.857G>A (p.Gly286Asp) | Missense | Rare (PMLD) | Loss of function; defective oligodendrocyte coupling |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Most PMLD-associated mutations (e.g., p.Gly12Asp, p.Gly286Asp) result in impaired gap junction formation or channel closure, leading to oligodendrocyte dysfunction.
Gain of Function (GOF)
Not reported for GJC2.
Dominant Negative (DN)
SPG44 mutations (e.g., p.Arg136Trp) produce mutant Cx47 that interferes with wild-type connexin assembly, reducing overall gap junction activity.
View complete mutation data：
Gene Ontology (GO)
| • connexin complex (GO:0005922) | • cell communication (GO:0007154) |
| • gap junction assembly (GO:0016264) | • myelination (GO:0042552) |
| • plasma membrane (GO:0005886) |
Pathways
• Gap junction trafficking and assembly (Reactome: R-HSA-190828)
• Oligodendrocyte specification and myelination (KEGG: hsa04530 – Tight junction; indirect)
Protein Summary
Connexin 47 (Cx47) is a 47 kDa transmembrane protein with four alpha-helical domains, two extracellular loops, and a cytoplasmic C-terminus. It forms homotypic and heterotypic gap junction channels, primarily with connexin 32 (GJB1) in oligodendrocytes and Schwann cells. Cx47 is critical for ionic and metabolic coupling between glial cells and axons. Defects in Cx47 disrupt myelin maintenance, leading to leukodystrophy and spastic paraplegia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJC2 Knockout HEK293 Cell Line | EDJ-KQ13600 | Human | 57165 | Details Get a Quote |
| GJC2 Knockout HeLa Cell Line | EDJ-KQ42010 | Human | 57165 | Details Get a Quote |
| GJC2 Knockout A-549 Cell Line | EDJ-KQ65327 | Human | 57165 | Details Get a Quote |
| GJC2 Knockout HCT 116 Cell Line | EDJ-KQ73764 | Human | 57165 | Details Get a Quote |
