GJB4 (Gap Junction Protein Beta 4)
Gene encoding connexin 30.3, involved in skin barrier function and deafness
Gene Information Card
| Symbol | GJB4 |
|---|---|
| Full Name | Gap junction protein beta 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 2707 ncbi.nlm.nih.gov/gene/2707 |
| Ensembl ID | ENSG00000189433 |
| UniProt ID | O95452 |
| OMIM ID | 605425 |
| HGNC ID | 4287 |
| Aliases | CX30.3, connexin 30.3, gap junction beta-4 protein |
Description
GJB4 encodes connexin 30.3, a member of the connexin family of gap junction proteins. Connexins form hexameric hemichannels that assemble into gap junctions, mediating intercellular communication. GJB4 is primarily expressed in the skin (epidermis) and inner ear, playing a critical role in keratinocyte differentiation and cochlear function. Mutations in GJB4 are associated with erythrokeratodermia variabilis (EKV) and autosomal dominant deafness.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Erythrokeratodermia variabilis (EKV) | Missense mutations in GJB4 disrupt gap junction assembly in keratinocytes, leading to abnormal skin barrier and erythematous plaques. | OMIM #133200; ClinVar |
| Autosomal dominant deafness (DFNA2-like) | Mutations in GJB4 impair cochlear gap junction function, affecting potassium recycling and auditory transduction. | OMIM #605425; ClinVar |
| Erythrokeratodermia variabilis et progressiva (EKVP) | Overlapping phenotype with EKV; GJB4 mutations cause progressive hyperkeratosis and erythema. | OMIM #133200; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Esophagus | 8.3 | Low |
| Cervix | 6.1 | Low |
| Vagina | 5.4 | Low |
| Tongue | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 18.7 | High expression in immortalized keratinocytes |
| A431 (epidermoid carcinoma) | 9.2 | Moderate expression |
| HEK293 (embryonic kidney) | 1.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.35G>A (p.Gly12Asp) | Missense | Rare | Dominant-negative effect; associated with EKV |
| c.94C>T (p.Arg32Trp) | Missense | Rare | Loss of function; associated with deafness |
| c.223G>A (p.Gly75Arg) | Missense | Rare | Dominant-negative; associated with EKV |
| c.560G>A (p.Arg187Gln) | Missense | Rare | Gain of function; associated with EKV |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg32Trp impair hemichannel formation or trafficking, reducing gap junction communication in cochlear cells.
Gain of Function (GOF)
Mutations like p.Arg187Gln increase hemichannel opening, leading to aberrant ion flux and cell death in keratinocytes.
Dominant Negative (DN)
Mutations such as p.Gly12Asp and p.Gly75Arg interfere with wild-type connexin assembly, disrupting gap junction plaques in skin.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Gap junction trafficking (Reactome: R-HSA-190828)
• Cell-cell communication (KEGG: hsa04540)
• Keratinocyte differentiation (WikiPathways: WP4620)
Protein Summary
Connexin 30.3 (Cx30.3) is a 266-amino acid transmembrane protein with four alpha-helical domains, two extracellular loops, and a cytoplasmic C-terminus. It forms hexameric hemichannels that dock with adjacent cells to create gap junctions. In the epidermis, Cx30.3 is essential for calcium-mediated keratinocyte differentiation and barrier formation. In the inner ear, it contributes to potassium ion recycling in the stria vascularis. Mutations disrupt channel gating or trafficking, leading to skin disorders or hearing loss.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJB4 Knockout HEK293 Cell Line | EDJ-KQ1887 | Human | 127534 | Details Get a Quote |
| GJB4 Knockout HCT 116 Cell Line | EDJ-KQ20482 | Human | 127534 | Details Get a Quote |
| GJB4 Knockout HeLa Cell Line | EDJ-KQ58209 | Human | 127534 | Details Get a Quote |
| GJB4 Knockout A-549 Cell Line | EDJ-KQ66700 | Human | 127534 | Details Get a Quote |
