GJB1

Chr XXLD

gap junction protein beta 1

Also known as: CMTX, CMTX1, CX32

The protein forms gap junction channels that facilitate transfer of ions and small molecules between cells. Mutations cause X-linked dominant Charcot-Marie-Tooth neuropathy type 1, an inherited peripheral neuropathy. The predicted mechanism of pathogenicity is gain-of-function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
GOFmechanismXLDLOEUF 0.491 OMIM phenotype
Clinical SummaryGJB1
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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.
📖
GeneReview available — GJB1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.846
Z-score 2.30
OE 0.00 (0.000.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.03Z-score
OE missense 0.50 (0.410.62)
66 obs / 131.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.49)
00.351.4
Missense OE0.50 (0.410.62)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 0 / 6.2Missense obs/exp: 66 / 131.4Syn Z: 0.41
DN
0.5868th %ile
GOF
0.76top 25%
LOF
0.51top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗