Overview
GJB6 encodes Connexin 30, a gap junction protein that works closely with Connexin 26 (GJB2) in the inner ear. Connexin 30, together with Connexin 26, forms gap junctions in the cochlea that are essential for potassium recirculation. Mutations in GJB6, often in combination with GJB2 mutations, lead to non-syndromic deafness (digenic inheritance).
13q12.11 (Chromosome 13, adjacent to GJB2)
Hereditary Diseases
Autosomal recessive
Often in combination with GJB2 mutations
Function & Significance
Connexin 30 forms hemichannels that connect with hemichannels of adjacent cells to form gap junctions. In the inner ear, Connexin 30 works closely with Connexin 26 to form a network of gap junctions that maintains potassium homeostasis.
The most common GJB6 mutation is a large deletion (del(GJB6-D13S1830)) that removes the entire GJB6 gene. This deletion is often found together with GJB2 mutations (compound heterozygosity or digenic inheritance), leading to deafness.
🔬 Digenic Inheritance
GJB6 and GJB2 are located close to each other on chromosome 13 and work together functionally. Therefore, mutations in both genes can act together to cause deafness. For example, a patient may inherit a 35delG mutation in GJB2 from one parent and a del(GJB6-D13S1830) deletion from the other parent, resulting in deafness.
Associated Diseases
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👂 Non-syndromic Deafness DFNB1
Congenital sensorineural deafness without further symptoms, often in combination with GJB2 mutations
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🧒 Congenital Deafness
Deafness from birth, bilateral
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🩺 Ectodermal Dysplasia (rare)
With certain mutations: skin changes in addition to deafness
🧬 Relevant SNPs
The most common GJB6 mutation is a large deletion: del(GJB6-D13S1830), also known as del(13q12). This deletion removes the entire GJB6 gene and is often found together with GJB2 mutations. Other mutations are rarer.
⚕️ Clinical Significance
Diagnosis: GJB6 mutations are often tested as part of a comprehensive deafness panel that includes GJB2. The del(GJB6-D13S1830) deletion requires special PCR tests, as it is not detected by standard sequencing.
Management: Identical to GJB2-associated deafness:
- Cochlear Implants: Very effective
- Hearing Aids: For milder forms
- Early Language Support: Sign language and/or spoken language
Genetic Counseling: Important, as GJB6 mutations are often combined with GJB2 mutations. Carriers of GJB6 deletions should also be tested for GJB2 mutations.
📚 Data Sources
The information on this page is based on the following scientific sources:
- OMIM: #604418 (GJB6), #220290 (Deafness, Autosomal Recessive 1A)
- ClinVar: Pathogenic GJB6 variants
- PubMed: Literature on GJB6 and deafness
- Orphanet: ORPHA90635 (Autosomal recessive non-syndromic sensorineural deafness type DFNB)
Last Update: February 2026