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Symbol GJA1 contributors: shn - updated : 23-09-2016
HGNC name gap junction protein, alpha 1, 43kDa
HGNC id 4274
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheartatrium  highly Homo sapiens
 vessel     Homo sapiens
Reproductivemale systemtestis  predominantly Homo sapiens
 male systemmale genital tractepididymis   Homo sapiens
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumcardiacmyocardiumpredominantly Homo sapiens
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/ImmuneB cell
Lymphoid/ImmuneT cell
Muscularmyocyte Homo sapiens
cell lineage
cell lines 76N and 81N cells
physiological period fetal
cell cycle     cell cycle
Text cochlea, heart
  • four membrane spanning alpha helices, separating the N terminal intracellular domain
  • two extracellular loops
  • the 241-382 AAs region required for interaction with BAX
  • a C terminal intracellular domain, interacting with C-terminus of GJA5 (interaction important for the regulation of heteromeric channels)
  • mono polymer heteromer
    interspecies ortholog to Gja1, Mus musculus
    ortholog to Gja1, Rattus norvegicus
    ortholog to gja1, Xenopus (Silurana) tropicalis
    ortholog to GJA1, Pan troglodytes
  • connexin family
  • alpha-type (group II) subfamily
  • CATEGORY adhesion , structural protein , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,gap
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text localized in cardiomyocyte mitochondria, at least in part in the inner mitochondrial membrane, where it is imported by the general mitochondrial membrane translocase system
    basic FUNCTION
  • cytoplasmic tail domain of connexin 43 is an important determinant of the unitary conductance event of gap junction channels
  • Cx43 plays an essential role in heart development
  • member of the connexin of intercellular channels, providing a route for the diffusion of materials of low molecular weight from cell to cell
  • contributes to retinal pigment epithelial cells differentiation via cAMP signaling
  • promotes the formation and growth of gap junctional plaques
  • CX43-mediated gap junctions may serve as conduits for the spread of proinflammatory signals in the lung capillary bed
  • CX43 is necessary for glial-guided neuronal migration
  • mediates the expression of an array of genes involved in cardiogenesis, in addition to intercellular communication
  • GJA1 plays a key role in eye development and in the development of glaucoma
  • plays a role in protection during myocardial ischaemic and pharmacological preconditioning and this role is independent from gap junction-mediated communication
  • can mediate cell–cell communication
  • involved in conferring cell adhesion in the seminiferous epithelium
  • crucial for ight junctions reassembly at the BTB (blood–testis barrier) during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis
  • crucial for the reassembly of the disrupted Sertoli cell TJ-permeability barrier
  • may be responsible for the necessary crosstalk between different junction complexes to maintain their adhesive function and to coordinate different junctions to maintain the immunological barrier integrity during the transit of preleptotene spermatocytes
  • local regulation of monocyte GJA1 activity within the vasculature can dynamically modulate the monocyte–endothelial adhesion that is an initiating event in vascular inflammatory pathologies
  • GJA1 function in monocytes rapidly decreases adhesion via ATP release
  • seems to be a pivotal player in defining how well and where monocytes will adhere to endothelial cells and thereby promote atherosclerotic development and progression of other vascular pathologies
  • regulates the passage of migrating neurons through their multipolar stage via CDKN1B signaling and interference with this process, by either genetic and/or environmental factors, may cause cortical malformations
  • exerts a protective role and regulates the Hematopoietic stem cell (HSC)/progenitors ROS content through ROS transfer to the hematopoietic microenvironment (HM), resulting in HSC protection during stress hematopoietic regeneration
  • is more than a passive channel; rather, it actively participates in the generation and modulation of cellular signals that drive skeletal development and homeostasis
  • involvement in mechanotransduction of fluid shear stress and in the modulation of mechanical loading-related apoptosis, osteogenesis, and osteoclastogenesis of osteocytes
    PHYSIOLOGICAL PROCESS endocytosis transport
    signaling sensory transduction/hearing , sensory transduction/vision
    may be participating in the recycling of potassium to the cochlear endolymph
    a component
  • monomer constituent of the connexon (six subunits), docking with its counterpart in the neighboring cell to form the gap junction channel
  • protein complex consisting of GJA1 and plakophilin-2 (PKP2) at the desmosome-like junction
  • is a SUMOylation target protein and represent the first evidence that gap junctions are regulated by the SUMO system
    small molecule
  • tight junction protein 1, TJP1 (Giepmans et al, 1998)
  • TJP1 and gap junction protein, gamma 1, 45kDa (GJC1) in osteoblastic cells
  • gap junction protein alpha 3 46kDa, GJA3
  • gap junction protein alpha 5 40kDa, GJA5
  • caveolin 1 caveolae protein 22kDa, CAV1
  • casein kinase 1, CK1
  • mitogen-activated protein kinase 7, MAPK7
  • nephroblastoma overexpressed gene, NOV
  • connexin 43-interacting protein, 150kD (CIP150)
  • Cx43-interacting protein of 85-kDa, CIP85
  • desmosomal protein PKP2 (form a protein complex within the desmosome-like junction to regulate cell adhesion at the blood–testis barrier, partly through its effects on the occludin/ZO-1 complex, so as to facilitate the transit of primary preleptotene spermatocytes)
  • interacting with ERP29 (new role for ERP29 as a chaperone that helps stabilize monomeric GJA1 to enable oligomerization to occur in the Golgi apparatus)
  • binding of the growth regulator CCN3 (NOV) at the C-terminus of GJA1
  • TBX18 directly represses the GJA1 promoter
  • is a downstream target molecule of NONO
  • can regulate GJA1 expression at the transcription level and decreases in POR reduce gap junctional intercellular communication, as well as hemichannel activity
  • TCF12 functions as a regulator of EMT by affecting the expression of CDH1 as well as that of GJA1 and GJB2
  • GJA1-mediated GJB1 and SLC1A5 interaction play important functional roles in trophoblast cell fusion
  • CASK directly interacts with GJA1
  • integrin alpha5beta1 interacts directly with GJA1 and this interaction is required for mechanical stimulation-induced opening of the GJA1 hemichannel
  • both SENP1 and -2 induce deSUMOylation of GJA1
  • regulates the passage of migrating neurons through their multipolar stage via CDKN1B signaling
  • MAPK-phosphorylated GJA1 is a novel interacting partner of cyclin E in VSMC (vascular smooth muscle cells) and this interaction is critical for VSMC proliferation
  • in the context of apoptosis, translocated to the mitochondria, where it interacted with BAX to initiate the mitochondrial apoptotic pathway
  • associates with SCN5A in the cardiomyocyte perinexus
  • NR1D1 activates GJA1 transcription by forming a complex with SP1
  • CTTNBP2NL dephosphorylated GJA1
  • oocyte-derived BMP15 decreases GJA1 activity between human granulosa cells by down-regulating Cx43 expression, most likely via a Smad-dependent signaling pathway
  • PPP2R2A is required for GJA1 dephosphorlyation during epidermal barrier acquisition
  • interaction between the T-cell protein tyrosine phosphatase (PTPN2) and the C-terminus of connexin43 (GJA1)
  • PRKAA1 stimulates ubiquitination of the gap junction protein GJA1, thereby contributing to gap junction remodeling following pressure overload
  • intermittent hypoxia causes reductions and remodeling of atrial GJA5, GJA1, generated in response to reactive oxygen species
  • by CYBB, and likely contributing to the substrate for atrial fibrillation that develops in response to obstructive sleep apnea
  • EXOSC10 was likely required for CELF1-mediated GJA1 mRNA degradation
  • EZR-anchored PRKACA phosphorylates serine 369 and 373 on GJA1 to enhance gap junction assembly, communication, and cell fusion
  • absence of CLMP caused a severe reduction of GJA1, GJC1 in smooth muscle cells of the intestine and of GJA1 in the ureter
  • GJA1 controls neural crest cell migration by directly regulating CDH2 transcription
  • cell & other
    activated by phytohaemagglutinin(PHA) and lipopolysaccharide (LPS)
    repressed by TJP1 (plays a role in the down-regulation and decreased size of GJA1 gap junctions in congestive heart failure)
    TBX18 overexpression that specifically and significantly down-regulates GJA1, and suppression of GJA1 by TBX18 occurs in adult ventricular myocardium as well as in neonatal cardiomyocytes, and the down-regulation persists even after TBX18 expression fades
    IRX3, that directly represses GJA1 transcription
    Phosphorylated by TYK2 that can also inhibit gap junction communication by phosphorylating GJA1 (
  • phosphorylated by v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (v-src)
  • phosphorylated byprotein kinase C, PKC
  • posttranslationally modified by SUMOylation
    corresponding disease(s) DFNB34 , ODDD , HLHS1 , SDTY3 , CMDR , AVSD3 , EKVP3
    related resource Hereditary Hearing Loss Homepage
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer cell (marker for detecting early oncogenesis in the breast)
    constitutional     --low  
    in congestive heart failure (contributing to contractile dysfunction)
    in the heart results in sudden arrhythmic death due to increased gap junctional resistance and slowed conduction velocity, which form a substrate for re-entrant arrhythmias
    constitutional     --low  
    in azoospermic men decreased expression of EGFR may be responsible for decreasing GJA1 levels and increasing its cytosolic localization via the PI3K/AKT signaling pathway
    Susceptibility to Atrial Fibrillation (AF)
    Variant & Polymorphism SNP GJA1 variant rs13216675 associated with AF
    Candidate gene
    Therapy target
    target for research into the treatment of various eye diseases due to RPE dysfunction
  • CX43 mutant embryos died at birth as a result of a failure in pulmonary gas exchange caused by a swelling and blockage of the right ventricular outflow tract from the hear
  • mice homozygous for CX43 exhibit an abnormal cardiac morphogenetic process
  • lack of expression of CX43 during embryogenesis compromising terminal stages of primary T and B cells differentiation
  • Blood pressure and heart rate measurements were significantly lower in the Cx43 knockout mice
  • mice lacking the C-terminal region of connexin-43 died shortly after birth. Female mice lacking the C-terminal region of connexin-43 are infertile due to impaired folliculogenesis
  • mouse model of ODDD (heterozygous for the human I130T mutation) showed a reduced Cx43 expression in hearts with preferential loss of phosphorylated forms, resulting in interference with trafficking and with assembly of gap junctions in the junctional membrane
  • adult Sertoli cell-specific Cx43 knockout (SC-Cx43 KO) mice displayed spermatogenic arrest at the spermatogonial level