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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GJC1
gap junction protein gamma 1
Chromosome 17 · 17q21.31
NCBI Gene: 10052Ensembl: ENSG00000182963.12HGNC: HGNC:4280UniProt: P36383
61PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingplasma membranegap junction channel activity involved in AV node cell-bundle of His cell electrical couplingcell-cell signalingneurodegenerative diseaseMyoclonuspolycystic ovary syndromeglioma
✦AI Summary

GJC1 (gap junction protein gamma 1, also known as connexin45) encodes a structural component of gap junctions, specialized intercellular channels that enable passage of small molecules and electrical signals between neighboring cells 1. GJC1 forms both homotypic and heterotypic channels and is expressed across diverse tissues including chondrocytes, cardiac tissue, and bladder 2. Beyond its canonical gap junction function, GJC1 mediates innate immune signaling by translocating second messengers like 2',3'-cGAMP between virus-infected cells and macrophages to amplify antiviral responses. Loss-of-function mutations in GJC1 impair channel coupling conductance and subcellular localization, contributing to cardiac arrhythmias; a heterozygous mutation (M235L) segregated with familial atrial fibrillation and conduction disease in a Chinese kindred 3. GJC1 has emerged as a potential oncogenic biomarker, with elevated expression in papillary thyroid carcinoma (AUC=0.982 in GEO dataset) and in liver cancer cells under high-glucose conditions, where O-GlcNAcylation-dependent mechanisms enhance proliferation 45. Additionally, de novo nonsense mutations in GJC1 have been identified in schizophrenia patients, with evidence suggesting GJC1 dysfunction may impair glutamatergic neuron ion channel regulation during prenatal neurodevelopment 6. GJC1 is also upregulated in overactive bladder tissue 7.

Sources cited
1
GJC1 (Cx45) is a structural component of gap junctions mediating intercellular electrical and metabolic communication
PMID: 33003547
2
GJC1 gap junction gene is expressed in chondrocytes from articular and costal cartilage
PMID: 27116676
3
GJC1 loss-of-function mutation (M235L) causes familial atrial fibrillation and cardiac conduction disease through impaired channel coupling
PMID: 33429106
4
GJC1 is highly expressed in papillary thyroid carcinoma with strong diagnostic value (AUC=0.982)
PMID: 40095160
5
High glucose stimulates GJC1 expression through O-GlcNAcylation-dependent mechanisms to enhance liver cancer cell proliferation
PMID: 30078215
6
De novo loss-of-function mutations in GJC1 identified in schizophrenia patients, with higher prenatal prefrontal cortex expression
PMID: 32873781
7
GJC1 is upregulated in overactive bladder tissue and involved in smooth muscle contraction pathways
PMID: 35932882
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.36Weak
MyoclonusOpen Targets
0.14Weak
polycystic ovary syndromeOpen Targets
0.10Weak
gliomaOpen Targets
0.08Suggestive
Abnormality of the skeletal systemOpen Targets
0.07Suggestive
hypertrophic cardiomyopathyOpen Targets
0.06Suggestive
left ventricular noncompactionOpen Targets
0.06Suggestive
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.06Suggestive
congenital heart diseaseOpen Targets
0.06Suggestive
dilated cardiomyopathy 1AAOpen Targets
0.05Suggestive
Atrial stand stillOpen Targets
0.05Suggestive
SplenomegalyOpen Targets
0.05Suggestive
sick sinus syndrome 2, autosomal dominantOpen Targets
0.05Suggestive
Familial dilated cardiomyopathy with conduction defect due to LMNA mutationOpen Targets
0.05Suggestive
dilated cardiomyopathyOpen Targets
0.05Suggestive
Glycogen storage disease due to glycogenin deficiencyOpen Targets
0.05Suggestive
glycogen storage disease XVOpen Targets
0.05Suggestive
left ventricular noncompaction 10Open Targets
0.05Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.05Suggestive
hypertrophic cardiomyopathy 6Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TJP1Protein interaction100%GJB6Protein interaction98%GJD2Protein interaction95%HCN4Protein interaction83%GJA4Protein interaction78%GJB1Protein interaction76%
Tissue Expression6 tissues
Heart
100%
Lung
37%
Brain
30%
Ovary
14%
Liver
5%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
GJC1TJP1GJB6GJD2HCN4GJA4GJB1
PROTEIN STRUCTURE
Preparing viewer…
PDB3SHW · 2.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.35Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.17 [0.09–0.35]
RankingsWhere GJC1 stands among ~20K protein-coding genes
  • #7,555of 20,598
    Most Researched61
  • #1,527of 17,882
    Most Constrained (LOEUF)0.35 · top 10%
Genes detectedGJC1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The expanding phenotypes of cohesinopathies: one ring to rule them all!
PMID: 31516082
Cell Cycle · 2019
1.00
2
Identification of GJC1 as a novel diagnostic marker for papillary thyroid carcinoma using weighted gene co-expression network analysis and machine learning algorithm.
PMID: 40095160
Discov Oncol · 2025
0.90
3
Membrane channel gene expression in human costal and articular chondrocytes.
PMID: 27116676
Organogenesis · 2016
0.80
4
Connexin45 (GJC1) loss-of-function mutation contributes to familial atrial fibrillation and conduction disease.
PMID: 33429106
Heart Rhythm · 2021
0.70
5
Identification of Cx45 as a Major Component of GJs in HeLa Cells.
PMID: 33003547
Biomolecules · 2020
0.60