GJB3 (Gap Junction Protein Beta 3)
Connexin 31: Genetic Insights into Hearing Loss and Skin Disorders
Gene Information Card
| Symbol | GJB3 |
|---|---|
| Full Name | Gap Junction Protein Beta 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 2707 ncbi.nlm.nih.gov/gene/2707 |
| Ensembl ID | ENSG00000188910 |
| UniProt ID | O75712 |
| OMIM ID | 603324 |
| HGNC ID | 4285 |
| Aliases | CX31, DFNA2, EKV, EKV1 |
Description
GJB3 (Gap Junction Protein Beta 3) encodes connexin 31, a transmembrane protein that forms gap junction channels facilitating intercellular communication. It is critical for cochlear function and epidermal differentiation. Mutations in GJB3 cause autosomal dominant non-syndromic hearing loss (DFNA2) and erythrokeratodermia variabilis (EKV).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Erythrokeratodermia variabilis (EKV) | Missense mutations disrupt connexin 31 assembly or channel function, leading to abnormal epidermal keratinocyte communication. | ClinVar, OMIM |
| Non-syndromic hearing loss (DFNA2) | Dominant mutations impair gap junction coupling in cochlear supporting cells, causing progressive sensorineural deafness. | ClinVar, OMIM |
| Deafness, autosomal dominant 2B (DFNA2B) | Specific GJB3 variants (e.g., p.R180X) truncate the protein, abolishing channel activity. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Cochlea | 8.2 | Medium |
| Esophagus | 6.1 | Low |
| Placenta | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocytes) | 15.3 | High expression in epidermal cells |
| HEK293 | 2.1 | Low endogenous expression |
| HeLa | 1.5 | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.95G>A (p.R32H) | Missense | Rare | Dominant negative; impairs channel conductance |
| c.538C>T (p.R180X) | Nonsense | Rare | Loss of function; truncation of C-terminus |
| c.263C>T (p.T88M) | Missense | Rare | Gain of toxic function; associated with EKV |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants (e.g., p.R180X) produce truncated connexin 31 unable to form functional channels.
Gain of Function (GOF)
Some missense mutations (e.g., p.T88M) may alter channel gating or permeability, contributing to EKV phenotype.
Dominant Negative (DN)
Missense variants (e.g., p.R32H) co-assemble with wild-type connexins, disrupting multimer formation and channel activity.
View complete mutation data：
Gene Ontology (GO)
| • gap junction (GO:0005922) | • gap junction channel activity (GO:0005243) |
| • cell communication (GO:0007154) | • sensory perception of sound (GO:0007605) |
| • epidermis development (GO:0008544) |
Pathways
• Gap junction trafficking and regulation (Reactome: R-HSA-190828)
• Connexin trafficking (KEGG: hsa04540)
Protein Summary
Connexin 31 (Cx31) is a 270-amino acid transmembrane protein with four alpha-helical domains, two extracellular loops, and cytoplasmic N- and C-termini. It oligomerizes into hexameric connexons that dock with adjacent cells to form gap junction channels. Cx31 is essential for potassium ion recycling in the cochlea and for coordinated keratinocyte differentiation in the epidermis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJB3 Knockout HEK293 Cell Line | EDJ-KQ3942 | Human | 2707 | Details Get a Quote |
| GJB3 Knockout A-549 Cell Line | EDJ-KQ27429 | Human | 2707 | Details Get a Quote |
| GJB3 Knockout HCT 116 Cell Line | EDJ-KQ27431 | Human | 2707 | Details Get a Quote |
| GJB3 Knockout HeLa Cell Line | EDJ-KQ27432 | Human | 2707 | Details Get a Quote |
| GJB3 (p.C165T) Point Mutation in HCT 116 Cell Line | EDC03054 | Human | 2707 | Details Get a Quote |
