GJB2 (Gap Junction Beta 2) - GeneticArchaelogy

Overview

GJB2 encodes Connexin 26, a gap junction protein essential for potassium recirculation in the inner ear. Mutations in this gene are the most common genetic cause of congenital deafness worldwide. The 35delG mutation alone is responsible for 50-80% of all autosomal recessive deafness cases in Caucasian populations.

📍 Chromosomal Position

13q12.11 (Chromosome 13)

🧬 Gene Category

Hereditary Diseases

🔬 Inheritance

Autosomal recessive

📊 Prevalence

Carrier frequency 2-4% in Europe; most common genetic cause of deafness

Function & Significance

Connexin 26 forms gap junctions (cell-to-cell channels) between the supporting cells of the cochlea in the inner ear. These channels allow the exchange of potassium ions and small molecules between neighboring cells. Potassium recirculation is essential for maintaining the endocochlear potential necessary for sound perception.

In mutations in GJB2, gap junction function is disrupted. This leads to an accumulation of potassium ions in the cochlea, which damages hair cells and leads to sensorineural hearing loss. Deafness is typically congenital (from birth) and non-progressive, but in rare cases, it can also appear later or worsen.

🔬 Gap Junctions in the Inner Ear

Gap junctions are specialized cell connections composed of connexin proteins. In the inner ear, Connexin 26 (GJB2) and Connexin 30 (GJB6) form a network that maintains potassium homeostasis. Disruptions in this system lead to the death of hair cells and thus to irreversible hearing loss.

Associated Diseases

👂 Non-syndromic Deafness DFNB1

Congenital sensorineural deafness without further symptoms. Severity varies from mild to profound.
🧒 Congenital Deafness

Deafness from birth, often bilateral (both ears) and severe to profound
🔊 Late-Onset Deafness

Rarer: progressive hearing loss in childhood or adulthood
🩺 Keratitis-Ichthyosis-Deafness Syndrome (KID)

Rare syndromic form with skin changes (only with specific mutations)

🧬 Relevant SNPs

rs80338939
13:20189539

Allele 1

Allele 2

–

Significance: 35delG (c.35delG) – Most common GJB2 mutation worldwide. Frameshift mutation leads to a premature stop codon and a non-functional protein. Responsible for 50-80% of all autosomal recessive deafness cases in Caucasian populations. Particularly common in Southern Europe and the Mediterranean region.

rs111033186
13:20189576

Allele 1

Allele 2

–

Significance: 167delT – Another common deletion, especially in Ashkenazi Jewish populations. Also leads to frameshift and non-functional protein.

⚕️ Clinical Significance

GJB2 mutations are included in newborn hearing screening in many countries. Early diagnosis is critical for language development. Affected children benefit from:

Cochlear Implants: Very effective in GJB2-associated deafness
Hearing Aids: For milder forms
Early Language Support: Sign language and/or spoken language

Gene Therapy Research: Promising preclinical studies for gene therapy for GJB2 mutations are ongoing. Initial animal studies show restoration of hearing function.

Genetic Counseling: Carriers have a 25% risk per pregnancy of having a deaf child. Prenatal diagnosis is possible.

📚 Data Sources

The information on this page is based on the following scientific sources:

OMIM: #220290 (Deafness, Autosomal Recessive 1A)
dbSNP: rs80338939 (35delG), rs111033186 (167delT)
ClinVar: Pathogenic GJB2 variants
PubMed: Literature on GJB2 and congenital deafness
Orphanet: ORPHA90635 (Autosomal recessive non-syndromic sensorineural deafness type DFNB)
Hereditary Hearing Loss Homepage: hereditaryhearingloss.org

Last Update: February 2026

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GJB2