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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GJA1
gap junction protein alpha 1
Chromosome 6 Β· 6q22.31
NCBI Gene: 2697Ensembl: ENSG00000152661.10HGNC: HGNC:4274UniProt: P17302
773PubMed Papers
28Diseases
0Drugs
60Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
monoatomic ion transmembrane transportfocal adhesiongap junction channel activitygap junctionoculodentodigital dysplasiaerythrokeratodermia variabilisoculodentodigital dysplasia, autosomal recessiveautosomal dominant palmoplantar keratoderma and congenital alopecia
✦AI Summary

GJA1 encodes connexin 43 (Cx43), a critical gap junction protein mediating intercellular communication through both electrical coupling and direct molecular transfer. As a structural component of gap junctions, Cx43 forms channels allowing passage of small molecules and ions between adjacent cells 12. Beyond classical gap junction functions, GJA1 mediates translocation of second messengers (2',3'-cGAMP and 2',5'-oligoadenylates) between virus-infected and uninfected cells, amplifying antiviral immune responses through innate immune signaling pathways. Recent functional studies reveal GJA1's role in intercellular mitochondrial transfer. Cx43 expression in mesenchymal stromal cells correlates with mitochondrial transfer to chondrocytes under oxidative stress, with the GJA1-20k isoform particularly potent at mediating this transfer 1. Similarly, megakaryocyte-derived mitochondria transfer to bone marrow MSCs through Cx43 gap junctions, reducing platelet activation 2. GJA1 expression also regulates mechanical force transmission during parturition; PIEZO channel-mediated mechanotransduction controls Cx43 expression in uterine smooth muscle, essential for labor progression 3. In reproductive tissues, CXCL10 disrupts GJA1 homeostasis between oocytes and granulosa cells, inhibiting follicular development in polycystic ovary syndrome 4. Clinically, GJA1 modulation affects cardiac electrophysiology and cardiometabolic health markers 56. GJA1 silencing decreases proliferation and increases apoptosis of spermatogonial stem cells through KLF2-mediated regulation, implicating GJA1 in male fertility 7.

Sources cited
1
Cx43 (GJA1) expression mediates mitochondrial transfer from mesenchymal stromal cells to chondrocytes; GJA1-20k isoform highly correlates with mitochondrial transfer incidence
PMID: 39390589
2
Cx43 gap junctions on MSCs mediate mitochondrial transfer from megakaryocytes; heme exposure in sickle cell disease decreases Cx43 expression and mitochondrial uptake
PMID: 40014405
3
PIEZO channel-mediated mechanotransduction reduces connexin43 (Gja1) expression in uterine smooth muscle, impairing labor progression
PMID: 41231991
4
CXCL10 disrupts GJA1 homeostasis between oocytes and granulosa cells, inhibiting follicular development and ovulation in PCOS
PMID: 39107809
5
GJA1 modulation using CRISPRi affects cardiac repolarization, resting membrane potential stability, and conduction properties in human iPSC-cardiomyocytes
PMID: 38062109
6
GJA1 expression in adipose tissue shows depot-specific regulation and context-dependent associations with cardiometabolic traits
PMID: 41275133
7
KLF2 inhibits proliferation and enhances apoptosis of human spermatogonial stem cells by targeting GJA1
PMID: 38352225
Disease Associationsβ“˜28
oculodentodigital dysplasiaOpen Targets
0.86Strong
erythrokeratodermia variabilisOpen Targets
0.77Strong
oculodentodigital dysplasia, autosomal recessiveOpen Targets
0.75Strong
autosomal dominant palmoplantar keratoderma and congenital alopeciaOpen Targets
0.73Strong
syndactyly type 3Open Targets
0.70Strong
craniometaphyseal dysplasia, autosomal recessiveOpen Targets
0.68Moderate
hypoplastic left heart syndrome 1Open Targets
0.62Moderate
Hallermann-Streiff syndromeOpen Targets
0.60Moderate
familial atrioventricular septal defectOpen Targets
0.50Moderate
hereditary cardiac anomalyOpen Targets
0.50Moderate
atrial fibrillationOpen Targets
0.49Moderate
genetic disorderOpen Targets
0.48Moderate
congenital left-sided heart lesionsOpen Targets
0.48Moderate
hypoplastic left heart syndromeOpen Targets
0.48Moderate
Spastic paraplegiaOpen Targets
0.46Moderate
TachycardiaOpen Targets
0.41Moderate
craniometaphyseal dysplasiaOpen Targets
0.37Weak
syndactyly type 5Open Targets
0.34Weak
Anteverted naresOpen Targets
0.34Weak
Bilateral microphthalmosOpen Targets
0.34Weak
Craniometaphyseal dysplasia, autosomal recessiveUniProt
Erythrokeratodermia variabilis et progressiva 3UniProt
Hallermann-Streiff syndromeUniProt
Hypoplastic left heart syndrome 1UniProt
Oculodentodigital dysplasiaUniProt
Oculodentodigital dysplasia, autosomal recessiveUniProt
Palmoplantar keratoderma and congenital alopecia 1UniProt
Syndactyly 3UniProt
Pathogenic Variants60
NM_000165.5(GJA1):c.412G>A (p.Gly138Ser)Pathogenic
Oculodentodigital dysplasia, autosomal recessive|Oculodentodigital dysplasia
β˜…β˜…β˜†β˜†2025β†’ Residue 138
NM_000165.5(GJA1):c.413G>A (p.Gly138Asp)Pathogenic
Oculodentodigital dysplasia, autosomal recessive|Oculodentodigital dysplasia
β˜…β˜…β˜†β˜†2025β†’ Residue 138
NM_000165.5(GJA1):c.226C>A (p.Arg76Ser)Pathogenic
Oculodentodigital dysplasia|not provided|Oculodentodigital dysplasia, autosomal recessive
β˜…β˜…β˜†β˜†2025β†’ Residue 76
NM_000165.5(GJA1):c.65G>A (p.Gly22Glu)Pathogenic
Oculodentodigital dysplasia|Oculodentodigital dysplasia, autosomal recessive
β˜…β˜…β˜†β˜†2024β†’ Residue 22
NM_000165.5(GJA1):c.443G>A (p.Arg148Gln)Pathogenic
Oculodentodigital dysplasia|not provided|Oculodentodigital dysplasia, autosomal recessive
β˜…β˜…β˜†β˜†2024β†’ Residue 148
NM_000165.5(GJA1):c.119C>T (p.Ala40Val)Pathogenic
Oculodentodigital dysplasia|8 conditions|Oculodentodigital dysplasia, autosomal recessive|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 40
NM_000165.5(GJA1):c.113G>A (p.Gly38Glu)Pathogenic
Oculodentodigital dysplasia, autosomal recessive|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 38
NM_000165.5(GJA1):c.131C>T (p.Ala44Val)Pathogenic
Erythrokeratodermia variabilis et progressiva 3|Oculodentodigital dysplasia, autosomal recessive
β˜…β˜…β˜†β˜†2022β†’ Residue 44
NM_000165.5(GJA1):c.142G>A (p.Glu48Lys)Pathogenic
Oculodentodigital dysplasia|Oculodentodigital dysplasia, autosomal recessive
β˜…β˜…β˜†β˜†2021β†’ Residue 48
NM_000165.5(GJA1):c.75G>C (p.Trp25Cys)Pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 25
NM_000165.5(GJA1):c.140A>T (p.Asp47Val)Pathogenic
Oculodentodigital dysplasia, autosomal recessive|not provided
β˜…β˜…β˜†β˜†2018β†’ Residue 47
NM_000165.5(GJA1):c.442C>G (p.Arg148Gly)Likely pathogenic
Oculodentodigital dysplasia, autosomal recessive
β˜…β˜†β˜†β˜†2025β†’ Residue 148
NM_000165.5(GJA1):c.460A>C (p.Thr154Pro)Likely pathogenic
Oculodentodigital dysplasia
β˜…β˜†β˜†β˜†2025β†’ Residue 154
NM_000165.5(GJA1):c.389T>C (p.Ile130Thr)Pathogenic
Oculodentodigital dysplasia, autosomal recessive
β˜…β˜†β˜†β˜†2025β†’ Residue 130
NM_000165.5(GJA1):c.402G>T (p.Lys134Asn)Likely pathogenic
Oculodentodigital dysplasia, autosomal recessive
β˜…β˜†β˜†β˜†2025β†’ Residue 134
NM_000165.5(GJA1):c.780_781del (p.Cys260fs)Pathogenic
Oculodentodigital dysplasia|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 260
NM_000165.5(GJA1):c.61G>A (p.Gly21Arg)Pathogenic
Oculodentodigital dysplasia|Oculodentodigital dysplasia, autosomal recessive
β˜…β˜†β˜†β˜†2025β†’ Residue 21
NM_000165.5(GJA1):c.53C>A (p.Ser18Ter)Pathogenic
Oculodentodigital dysplasia, autosomal recessive
β˜…β˜†β˜†β˜†2024β†’ Residue 18
NM_000165.5(GJA1):c.577C>G (p.Pro193Ala)Likely pathogenic
Oculodentodigital dysplasia, autosomal recessive
β˜…β˜†β˜†β˜†2024β†’ Residue 193
NM_000165.5(GJA1):c.679G>C (p.Glu227Gln)Pathogenic
Oculodentodigital dysplasia, autosomal recessive
β˜…β˜†β˜†β˜†2024β†’ Residue 227
View on ClinVar β†—
Related Genes
GJA8Protein interaction100%TUBB2AProtein interaction100%MAPK3Protein interaction99%TUBBProtein interaction99%TUBB3Protein interaction99%TUBB4BProtein interaction99%
Tissue Expression6 tissues
Heart
100%
Brain
48%
Ovary
11%
Lung
9%
Bone Marrow
1%
Liver
1%
Gene Interaction Network
Click a node to explore
GJA1GJA8TUBB2AMAPK3TUBBTUBB3TUBB4B
PROTEIN STRUCTURE
Preparing viewer…
PDB7Z1T Β· 2.26 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.52Moderately Constrained
pLIβ“˜
0.96Intolerant
Observed/Expected LoF0.30 [0.18–0.52]
RankingsWhere GJA1 stands among ~20K protein-coding genes
  • #257of 20,598
    Most Researched773 Β· top 5%
  • #1,160of 5,498
    Most Pathogenic Variants60 Β· top quartile
  • #3,228of 17,882
    Most Constrained (LOEUF)0.52 Β· top quartile
Genes detectedGJA1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes.
PMID: 39390589
Stem Cell Res Ther Β· 2024
1.00
2
PIEZO channels link mechanical forces to uterine contractions in parturition.
PMID: 41231991
Science Β· 2025
0.90
3
BCR-ABL1-driven exosome-miR130b-3p-mediated gap-junction Cx43 MSC intercellular communications imply therapies of leukemic subclonal evolution.
PMID: 37554265
Theranostics Β· 2023
0.86
4
Dissecting regulatory non-coding GWAS loci reveals fibroblast causal genes with pathophysiological relevance to heart failure.
PMID: 41073375
Nat Commun Β· 2025
0.84
5
Endothelial-adipocyte Cx43 Mediated Gap Junctions Can Regulate Adiposity.
PMID: 38984993
Function (Oxf) Β· 2024
0.82