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Symbol GJA5 contributors: mct - updated : 03-07-2015
HGNC name gap junction protein, alpha 5, 40kDa
HGNC id 4279
Corresponding disease
ATFB11 atrial fibrillation, familial, 11
Location 1q21.2      Physical location : 147.228.331 - 147.245.484
Synonym name
  • connexin 40
  • gap junction protein, alpha 5, 40kDa (connexin 40)
  • Synonym symbol(s) CX40, MGC11185, ATFB1A, ATFB11
    TYPE functioning gene
    STRUCTURE 17.15 kb     2 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure exon 1A (100 bp), exon 1B (132 bp) and coding exon 2, with the exons 1A and 1B at 14 and 1.3 kb of the exon 2, respectively
  • regulated by the interaction of ubiquitous and tissue-specific factors such as Sp1 and GATA4
  • MAPPING cloned Y linked N status confirmed
    Map cen - D1S514 - D1S442 - FMO5 - D1S2018E - GJA5- D1S2552 - D1S2612 - qter
    Physical map
    PIAS3 1q21 hypothetical protein DJ328E19.C1.1 RPC62 1q21.2 polymerase (RNA) III (DNA directed) (62kD) ZNF364 1q21.1 zinc finger protein 364 CD160 1q21.1 CD160 antigen PDZK1 1q21 PDZ domain containing 1 LOC388678 1 LOC388678 LOC391090 1 hypothetical gene supported by AB007923; AL833273 LOC200030 1q21.2 hypothetical protein LOC200030 LOC391091 1 similar to Profilin I LOC91632 1q21.2 similar to MGC5244 protein LOC388679 1 LOC388679 LOC388680 1 LOC388680 LOC388681 1 similar to KIAA0454 protein LOC388682 1 hypothetical gene supported by BC001289; NM_003142 PRKAB2 1q21 protein kinase, AMP-activated, beta 2 non-catalytic subunit LOC388683 1 hypothetical gene supported by NM_005313 FMO5 1q21.1 flavin containing monooxygenase 5 CHD1L 1q12 chromodomain helicase DNA binding protein 1-like BCL9 1q21 B-cell CLL/lymphoma 9 ACP6 1q21 lysophosphatidic acid phosphatase GJA5 1q21.1 gap junction protein, alpha 5, 40kDa (connexin 40) LOC391092 1 similar to Hypothetical protein DJ845O24.1 GJA8 1q21.1 gap junction protein, alpha 8, 50kDa (connexin 50) LOC388684 1 LOC388684 LOC388685 1 similar to hypothetical protein FLJ21308 COAS2 1q21.3 cyclophilin-LC DJ328E19.C1.1 1q12-1q21.2 hypothetical protein DJ328E19.C1.1 MGC8902 1q21.3 hypothetical protein MGC8902 LOC388686 1 similar to cyclophilin-LC; cyclophilin homolog overexpressed in liver cancer; chromosome 1 amplified sequence 2 LOC391093 1 similar to Profilin I
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3177 - 358 endothelial cells 2007 17189315
    2 - 3156 - 358 placental cytoytophoblast 2007 17189315
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartatrium  highly Homo sapiens
     vessel     Homo sapiens
    Urinarykidneyjuxtaglomerulus apparatus    Homo sapiens
     kidneynephronrenal capsuleBowman s capsule  Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac highly Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyocyte Homo sapiens
    cell lineage
    cell lines mesenchymal stem cells
    at STAGE
    physiological period pregnancy
    Text placental cytotrophoblast (variant B)
  • four putative membrane spanning alpha helices, separating the N terminal intracellular domain
  • two extracellular loops
  • a C terminal intracellular domain, interacting with C-terminus of GJA1 (interaction important for the regulation of heteromeric channels)
  • connexin family
  • alpha-type (group II) subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • oligomerize to form intercellular channels, called gap junctions, through which ions and small molecules move between adjacent cells
  • through both fast and slow gating mechanisms, exhibit a negative gating polarity
  • plays a predominant role in the formation of gap junctions in the vasculature, participates in the autoregulation of renal blood flow (RBF)
  • major gap-junction protein in the atrial myocardium
  • its expression plays a functional role in flow-driven arteriogenesis
  • central role potentially for the development and function of renin-producing cells and for tubuloglomerular signal transmission
  • plays an important role in signal propagation along blood vessel walls, modulating vessel diameter and thereby blood flow
    a component
  • monomer constituent of the connexon (six subunits), docking with its counterpart in the neighboring cell to form the gap junction channel
    small molecule
  • 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
  • cell & other
    inhibited by by inhibiting PI3K or AKT1, with PI3K activity being required for basal GJA5 expression and AKT1 activity taking part in its shear stress-dependent induction
    Other regulated by IRX3, that likely regulates GJA5 indirectly, activating GJA5 expression by suppressing the transcription of a GJA5 repressor
    corresponding disease(s) ATFB11
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in ischemic cardiomyopathy
    constitutional   deletion    
    1q21.1 contiguous gene deletion (with ACP6 and GJA8)associated with a range of cardiac defects, with particularly anomalies of the aortic arch
    constitutional somatic mutation      
    in idiopathic atrial fibrillation by impairing gap-junction assembly or electrical coupling
    constitutional   amplification    
    recurring copy-number variants in congenital heart disease
  • to atrial cardiomyopathy with heart block (see ATFB1A)
  • to essential hypertension in men
  • to Tetralogy of Fallot
  • Variant & Polymorphism other
  • somatic mutations in atrial cardiomyopathy with heart block
  • polymorphisms increasing the risk of essential hypertension in men
  • A96S mutation, the aberrant extravascular localization of renin-secreting cells in the kidney likely impairs the pressure-mediated inhibition of renin secretion, and is associated to essential hypertension
  • Candidate gene for the CHD phenotypes observed with dup 1q21
    Therapy target
  • deletion of the gap-junction-forming protein GJA5 leads to renin-dependent hypertension in mice
  • sinus node impulse initiation was found to be ectopic in Cx40(-/-) mice at 15.5 days postcoitus