GJB1

Chr X

gap junction protein beta 1

Also known as: CMTX, CMTX1, CX32

NCBI Gene: 2705ENSG00000169562UniProt: P08034

This gene encodes a member of the gap junction protein family. The gap junction proteins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and small molecules between cells. According to sequence similarities at the nucleotide and amino acid levels, the gap junction proteins are divided into two categories, alpha and beta. Mutations in this gene cause X-linked Charcot-Marie-Tooth disease, an inherited peripheral neuropathy. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

UniProtCharcot-Marie-Tooth disease, X-linked dominant, 1
UniProtDejerine-Sottas syndrome
594
ClinVar variants
167
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— GJB1
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease X-linked dominant 1 · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
167 Pathogenic / Likely Pathogenic· 299 VUS of 594 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.49LOEUF
pLI 0.846
Z-score 2.30
OE 0.00 (0.00–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.03Z-score
OE missense 0.50 (0.41–0.62)
66 obs / 131.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.41–0.62)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 0 / 6.2Missense obs/exp: 66 / 131.4Syn Z: 0.41

ClinVar Variant Classifications

594 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic104
Likely Pathogenic63
VUS299
Likely Benign102
Benign6
Conflicting20
104
Pathogenic
63
Likely Pathogenic
299
VUS
102
Likely Benign
6
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
27
42
2
104
Likely Pathogenic
7
49
7
0
63
VUS
27
231
38
3
299
Likely Benign
0
3
5
94
102
Benign
0
0
1
5
6
Conflicting
—20
Total6731093104594

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GJB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — GJB1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Charcot-Marie-Tooth: From Molecules to Therapy.
Morena J et al.·Int J Mol Sci
2019Review
Hereditary neuropathy.
Pisciotta C et al.·Handb Clin Neurol
2023Review
Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants.
Record CJ et al.·Brain
2023Natural history
Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease.
Record CJ et al.·Brain
2024
NCAM1 and GDF15 are biomarkers of Charcot-Marie-Tooth disease in patients and mice.
Jennings MJ et al.·Brain
2022Cohort
X-linked Charcot-Marie-Tooth disease.
Scherer SS et al.·J Peripher Nerv Syst
2012Review
Clinical spectrum and frequency of Charcot-Marie-Tooth disease in Italy: Data from the National CMT Registry.
Pisciotta C et al.·Eur J Neurol
2023
A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?
Kamińska J et al.·Int J Mol Sci
2024Review
Utility of genome sequencing in exome-negative pediatric patients with neurodevelopmental phenotypes.
Nomakuchi TT et al.·Am J Med Genet A
2024Cohort
Diseases of connexins expressed in myelinating glia.
Abrams CK·Neurosci Lett
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Specific variations in cfDNA methylation level of CDH1 and Gjb1 in a mouse model with breast cancer before and after metastasis.
Zhang Z et al.·Cancer Genet
2026Functional
Patient-derived neural organoids reveal developmental impairments associated with a novel GJB1 mutation in X-linked Charcot-Marie-Tooth disease.
Guo J et al.·Neurobiol Dis
2026
Comprehensive Analysis of GJB1 in Breast Cancer: Its Implications in Survival and Molecular Mechanisms.
Ozcivici E et al.·Anticancer Res
2024Functional
Hereditary spastic paraplegia and extensive leukoencephalopathy: a case report of a unique phenotype associated with a GJB1/Cx32 p.Pro174Ser variant.
Nakamura H et al.·BMC Neurol
2024🔓 Open AccessCase report
Novel Missense Mutation in GJB1 Gene Leading to X-linked Charcot-Marie-Tooth Disease in Young Male: A Case Report.
Patra P.·Neurol India
2024Case report
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools