GJA8 Gene - Gap Junction Protein Alpha 8
Genetic and functional insights into GJA8, encoding connexin 50, a key lens protein associated with cataracts and ocular development.
Gene Information Card
| Symbol | GJA8 |
|---|---|
| Full Name | Gap junction protein alpha 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.2 |
| NCBI Gene ID | 2703 ncbi.nlm.nih.gov/gene/2703 |
| Ensembl ID | ENSG00000121634 |
| UniProt ID | P48165 |
| OMIM ID | 600897 |
| HGNC ID | 4282 |
| Aliases | CX50, Cx50, MIP2, CAE1, CTRCT1 |
Description
GJA8 encodes connexin 50 (Cx50), a transmembrane protein that forms gap junction channels in the lens of the eye. These channels facilitate intercellular communication and are critical for lens transparency and homeostasis. Mutations in GJA8 are a common cause of autosomal dominant congenital cataracts and other lens opacities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant congenital cataract (ADCC) | Missense or frameshift mutations disrupt gap junction assembly or function, leading to lens opacity. | ClinVar, OMIM |
| Zonular pulverulent cataract | Specific GJA8 mutations (e.g., p.Arg23Thr) cause distinct cataract patterns. | OMIM, PubMed |
| Microcornea with cataract | Rare GJA8 variants impair lens development and corneal size. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lens | High | Tissue-specific high expression |
| Retina | Low | Detected in some studies |
| Brain | Not detected | No significant expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Lens epithelial cells (HLE-B3) | High | Primary expression site |
| ARPE-19 (retinal pigment epithelium) | Low | Minor expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.139G>A (p.Gly47Arg) | Missense | Rare | Dominant negative; disrupts channel function |
| c.560C>T (p.Pro187Leu) | Missense | Rare | Loss of function; associated with cataract |
| c.94C>T (p.Arg32Cys) | Missense | Rare | Gain of toxic function; severe cataract |
Mutation functional classification
Loss of Function (LOF)
Mutations that prevent proper connexin folding or trafficking, reducing gap junction coupling.
Gain of Function (GOF)
Rare variants that form hyperactive or leaky channels, causing cellular stress.
Dominant Negative (DN)
Common mechanism; mutant Cx50 subunits co-assemble with wild-type, impairing overall channel function.
View complete mutation data：
Gene Ontology (GO)
| • connexin complex (GO:0005922) | • cell communication (GO:0007154) |
| • gap junction channel activity (GO:0005243) | • lens development in camera-type eye (GO:0002088) |
| • gap junction assembly (GO:0016264) |
Pathways
• Gap junction trafficking and assembly (Reactome: R-HSA-190861)
• Cell-cell communication via connexins (KEGG: hsa04540)
Protein Summary
Connexin 50 (Cx50) is a 433-amino acid protein with four transmembrane domains, two extracellular loops, and cytoplasmic N- and C-termini. It oligomerizes into hexameric hemichannels (connexons) that dock with adjacent cell hemichannels to form gap junctions. Cx50 is essential for lens fiber cell homeostasis and transparency. Post-translational modifications include phosphorylation, which modulates channel gating.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJA8 Knockout HEK293 Cell Line | EDJ-KQ4709 | Human | 2703 | Details Get a Quote |
| GJA8 Knockout HeLa Cell Line | EDJ-KQ53347 | Human | 2703 | Details Get a Quote |
| GJA8 Knockout A-549 Cell Line | EDJ-KQ61826 | Human | 2703 | Details Get a Quote |
| GJA8 Knockout HCT 116 Cell Line | EDJ-KQ70313 | Human | 2703 | Details Get a Quote |
