GJB6 (Gap Junction Protein Beta 6)
Connexin 30: A Key Player in Hearing and Skin Disorders
Gene Information Card
| Symbol | GJB6 |
|---|---|
| Full Name | Gap Junction Protein Beta 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q12.11 |
| NCBI Gene ID | 10804 ncbi.nlm.nih.gov/gene/10804 |
| Ensembl ID | ENSG00000121742 |
| UniProt ID | O95452 |
| OMIM ID | 604418 |
| HGNC ID | 4288 |
| Aliases | CX30, DFNA3, DFNB1, EKV, HED2 |
Description
The GJB6 gene encodes connexin 30 (Cx30), a member of the connexin protein family that forms gap junction channels. These channels facilitate intercellular communication by allowing the direct transfer of ions and small molecules between adjacent cells. Connexin 30 is critical for cochlear function, where it supports potassium recycling necessary for hearing, and for epidermal differentiation in the skin. Mutations in GJB6 are associated with autosomal dominant and recessive nonsyndromic hearing loss (DFNA3/DFNB1) and Clouston syndrome (hidrotic ectodermal dysplasia).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nonsyndromic hearing loss (DFNA3/DFNB1) | Loss of functional gap junctions in the cochlea disrupts potassium ion recycling, impairing auditory transduction. | ClinVar, OMIM |
| Clouston syndrome (hidrotic ectodermal dysplasia) | Dominant-negative or gain-of-function mutations alter connexin 30 assembly, leading to abnormal epidermal differentiation and palmoplantar keratoderma. | OMIM, UniProt |
| Erythrokeratodermia variabilis (EKV) | Mutations in GJB6 cause defective gap junction communication in the skin, resulting in transient red patches and fixed hyperkeratotic plaques. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Cochlea | 8.2 | Medium |
| Esophagus | 6.8 | Low |
| Brain | 3.1 | Low |
| Heart | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocytes) | 15.3 | High expression; relevant for skin studies |
| HEK293 | 2.1 | Low endogenous expression |
| HeLa | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.31G>A (p.Gly11Arg) | Missense | Rare | Dominant-negative; associated with Clouston syndrome |
| c.263C>T (p.Thr88Met) | Missense | Rare | Gain-of-function; linked to erythrokeratodermia variabilis |
| c.35delG (frameshift) | Deletion | Common in hearing loss | Loss-of-function; causes DFNB1 recessive deafness |
| c.139G>T (p.Gly47Trp) | Missense | Rare | Dominant; associated with DFNA3 hearing loss |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations (e.g., c.35delG) abolish connexin 30 protein function, leading to recessive hearing loss (DFNB1).
Gain of Function (GOF)
Missense mutations (e.g., p.Thr88Met) enhance channel activity or alter gating, causing erythrokeratodermia variabilis.
Dominant Negative (DN)
Mutations such as p.Gly11Arg interfere with wild-type connexin assembly, resulting in Clouston syndrome.
View complete mutation data：
Gene Ontology (GO)
| • Gap junction channel activity (GO:0005243) | • Cell-cell signaling (GO:0007267) |
| • Protein homooligomerization (GO:0051260) | • Plasma membrane (GO:0005886) |
| • Connexin complex (GO:0005922) |
Pathways
• Gap junction trafficking and regulation (Reactome: R-HSA-190828)
• Potassium ion recycling in the cochlea (KEGG: hsa04742)
Protein Summary
Connexin 30 (Cx30) is a 261-amino acid transmembrane protein that oligomerizes into hexameric connexons (hemichannels). Two connexons from adjacent cells dock to form a gap junction channel. In the inner ear, Cx30 is expressed in supporting cells and fibrocytes, mediating potassium ion transport essential for hair cell function. In the skin, it is expressed in keratinocytes and contributes to epidermal homeostasis. The protein has four transmembrane domains, two extracellular loops, and cytoplasmic N- and C-termini.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GJB6 Knockout HEK293 Cell Line | EDJ-KQ2429 | Human | 10804 | Details Get a Quote |
| GJB6 Knockout HeLa Cell Line | EDJ-KQ55490 | Human | 10804 | Details Get a Quote |
| GJB6 Knockout A-549 Cell Line | EDJ-KQ63980 | Human | 10804 | Details Get a Quote |
| GJB6 Knockout HCT 116 Cell Line | EDJ-KQ72432 | Human | 10804 | Details Get a Quote |
