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GJB6
gap junction protein beta 6
The GJB6 gene encodes connexin 30, a protein vital for forming gap junctions that facilitate communication and transport between cells. The GJB6 gene provides instructions for creating connexin 30, a protein that forms gap junctions.
GJB6 is located on the long (q) arm of chromosome 13, at band 13q12.11. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 13 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The GJB6 gene, also known as gap junction protein beta 6, is responsible for producing connexin 30, a member of the connexin protein family. This protein is fundamental to cellular communication throughout the body by forming channels called gap junctions.
These gap junctions allow for the controlled passage of nutrients, ions, and signalling molecules between adjacent cells. The precise function and permeability of these channels are determined by the specific connexin proteins that comprise them.
What the gene does
Connexin 30, produced from the GJB6 gene, plays a critical role in cellular function by forming gap junctions. These structures act as direct conduits between neighbouring cells, enabling the transport of small molecules and ions. Gap junctions formed by connexin 30 are particularly adapted to transport potassium ions and specific small molecules.
Connexin 30 is found in various tissues, including the brain, skin, hair follicles, nail beds, and especially the inner ear. In the inner ear, its function is crucial for hearing, which relies on the accurate conversion of sound waves into electrical nerve impulses. This process requires maintaining precise potassium ion levels, a task in which connexin 30-formed gap junctions are thought to be involved. Some research suggests that gap junctions comprising connexin 30 assist in regulating potassium ion levels.
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Chromosome location
The GJB6 gene is located on chromosome 13 at position 13q12.11. This specific address on the long arm (q) of chromosome 13 indicates its genomic position within the human genome.
Protein structure
The GJB6 gene provides instructions for a protein that is 261 amino acids in length. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the GJB6 gene can alter the structure or function of the connexin 30 protein. These genetic changes can affect the proper formation or operation of gap junctions, leading to impaired cellular communication and transport processes. Such alterations are associated with various inherited conditions.
Sample of pathogenic variants
7 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.263C>T | p.Ala88Val | Pathogenic | ★★☆☆ | Autosomal recessive nonsyndromic hearing loss 1A |
c.31G>A | p.Gly11Arg | Pathogenic | ★★☆☆ | GJB6-related disorder |
g.(?_20797176)_21105944del | - | Pathogenic | ★☆☆☆ | Hidrotic ectodermal dysplasia syndrome |
c.31G>C | p.Gly11Arg | Pathogenic | ★☆☆☆ | Autosomal dominant nonsyndromic hearing loss 3B |
c.110T>A | p.Val37Glu | Pathogenic | - | Hidrotic ectodermal dysplasia syndrome |
c.14C>T | p.Thr5Met | Pathogenic | - | Autosomal dominant nonsyndromic hearing loss 3B |
c.261dup | p.Ala88fs | Pathogenic | - | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the GJB6 gene are primarily associated with inherited conditions affecting cell-to-cell communication. The Jeen Health database highlights Non-syndromic hearing loss (DFNB1), characterised by hearing impairment without other associated symptoms, as a key association. Medical literature also describes an association between GJB6 variants and Clouston syndrome, also known as hidrotic ectodermal dysplasia 2. This condition typically involves hair loss, fingernail abnormalities, and thickened skin on the palms and soles.
- Non-syndromic hearing loss (DFNB1) Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic GJB6 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The GJB6 gene is recognised within the UK's NHS Genomic Medicine Service, with several panels including it for genetic testing. It is featured on panels for Monogenic hearing loss (R67), Ectodermal dysplasia (R163), and Ichthyosis and erythrokeratoderma (R165), as well as panels for Ectodermal dysplasia without a known gene mutation and Palmoplantar keratoderma and erythrokeratodermas.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the GJB6 gene?
The GJB6 gene provides instructions for making connexin 30, a protein that forms gap junctions. These junctions are crucial for enabling cell-to-cell communication and transporting essential molecules and ions between cells.
How does the GJB6 gene relate to hearing?
Connexin 30, encoded by GJB6, is found in the inner ear. It is thought to play a role in maintaining the correct balance of potassium ions, which is vital for the conversion of sound waves into electrical nerve impulses necessary for hearing.
What conditions are associated with GJB6 gene variants?
Variants in the GJB6 gene are primarily associated with Non-syndromic hearing loss (DFNB1), as detailed in the Jeen Health database. Medical literature also indicates a link to Clouston syndrome, a disorder affecting hair, nails, and skin, though carrier screening primarily focuses on the hearing loss association.
References
- Xu J, Nicholson BJ. The role of connexins in ear and skin physiology - functional insights from disease-associated mutations. Biochimica et biophysica acta. 2013. PMID: 22796187
- Fujimoto A, Kurban M, Nakamura M. GJB6, of which mutations underlie Clouston syndrome, is a potential direct target gene of p63. Journal of dermatological science. 2013. PMID: 23219093
- Baris HN, Zlotogorski A, Peretz-Amit G. A novel GJB6 missense mutation in hidrotic ectodermal dysplasia 2 (Clouston syndrome) broadens its genotypic basis. The British journal of dermatology. 2008. PMID: 18717672
- Nickel R, Forge A. Gap junctions and connexins in the inner ear: their roles in homeostasis and deafness. Current opinion in otolaryngology & head and neck surgery. 2008. PMID: 18797288
- Marlin S, Feldmann D, Blons H. GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients. Archives of otolaryngology--head & neck surgery. 2005. PMID: 15967879
- Kibar Z, Dubé MP, Powell J. Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping. European journal of human genetics : EJHG. 2000. PMID: 10854098
- Lamartine J, Munhoz Essenfelder G, Kibar Z. Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nature genetics. 2000. PMID: 11017065
- Adam MP, Bick S, Mirzaa GM. Hidrotic Ectodermal Dysplasia 2. 1993. PMID: 20301379
- Adam MP, Bick S, Mirzaa GM. Nonsyndromic Hearing Loss and Deafness, DFNA3 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1993. PMID: 20301708