GJA3 (Gap Junction Protein Alpha 3)
A key lens-specific connexin gene associated with congenital cataracts and zonular pulverulent cataracts.
Gene Information Card
| Symbol | GJA3 |
|---|---|
| Full Name | Gap junction protein alpha 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 13q12.11 |
| NCBI Gene ID | 2700 ncbi.nlm.nih.gov/gene/2700 |
| Ensembl ID | ENSG00000121743 |
| UniProt ID | P48165 |
| OMIM ID | 121015 |
| HGNC ID | 4277 |
| Aliases | CX46, Cx46, gap junction alpha-3 protein, connexin 46 |
Description
GJA3 encodes connexin 46 (Cx46), a member of the connexin family that forms gap junction channels in the lens. These channels mediate intercellular communication essential for lens transparency and homeostasis. Mutations in GJA3 are a common cause of autosomal dominant congenital cataracts, particularly zonular pulverulent cataracts. The protein is expressed primarily in lens fiber cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital cataracts, autosomal dominant (CCAD) | Missense mutations disrupt gap junction assembly or channel function, impairing lens fiber cell communication and leading to opacification. | ClinVar, OMIM #121015 |
| Zonular pulverulent cataract 1 (CZP1) | Specific GJA3 mutations (e.g., p.Asn63Ser) cause a distinct cataract phenotype with pulverulent opacities in the lens nucleus and zonular region. | OMIM #601885 |
| Cataract, congenital, with microcornea | Rare GJA3 variants associated with reduced lens size and opacity. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lens | — | High |
| Retina | — | Low |
| Testis | — | Low |
| Brain | — | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Lens epithelial cells (HLE-B3) | — | Constitutive expression |
| Lens fiber cells (primary) | — | High expression |
| ARPE-19 (retinal pigment epithelium) | — | Low/absent |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.188A>G (p.Asn63Ser) | Missense | Common | Dominant negative; disrupts channel gating and trafficking |
| c.119C>T (p.Pro40Leu) | Missense | Rare | Loss of function; impaired gap junction formation |
| c.560G>A (p.Arg187His) | Missense | Rare | Dominant negative; reduced intercellular coupling |
| c.34G>A (p.Gly12Arg) | Missense | Rare | Gain of toxic function; ER retention and apoptosis |
Mutation functional classification
Loss of Function (LOF)
Rare; some missense variants (e.g., p.Pro40Leu) reduce channel conductance or prevent proper membrane localization.
Gain of Function (GOF)
Not well established; p.Gly12Arg may induce ER stress and cell death, but not classical gain-of-function.
Dominant Negative (DN)
Common mechanism; mutant Cx46 subunits co-assemble with wild-type, impairing gap junction function (e.g., p.Asn63Ser, p.Arg187His).
View complete mutation data：
Gene Ontology (GO)
Pathways
• Gap junction trafficking and assembly
• Lens fiber cell differentiation and homeostasis
• Intercellular calcium wave propagation
Protein Summary
Connexin 46 (Cx46) is a 435-amino acid transmembrane protein with four transmembrane domains, two extracellular loops, and cytoplasmic N- and C-termini. It forms hexameric hemichannels (connexons) that dock with opposing hemichannels to create gap junction channels. Cx46 is essential for lens transparency; mutations cause cataract by disrupting channel function, trafficking, or stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJA3 Knockout HEK293 Cell Line | EDJ-KQ4714 | Human | 2700 | Details Get a Quote |
| GJA3 Knockout HCT 116 Cell Line | EDJ-KQ27434 | Human | 2700 | Details Get a Quote |
| GJA3 Knockout HeLa Cell Line | EDJ-KQ53344 | Human | 2700 | Details Get a Quote |
| GJA3 Knockout A-549 Cell Line | EDJ-KQ61823 | Human | 2700 | Details Get a Quote |
