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    GJA1 gap junction protein alpha 1 [ Homo sapiens (human) ]

    Gene ID: 2697, updated on 22-Apr-2017
    Official Symbol
    GJA1provided by HGNC
    Official Full Name
    gap junction protein alpha 1provided by HGNC
    Primary source
    HGNC:HGNC:4274
    See related
    Ensembl:ENSG00000152661 MIM:121014; Vega:OTTHUMG00000015479
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HSS; CMDR; CX43; EKVP; GJAL; ODDD; AVSD3; HLHS1; PPKCA
    Summary
    This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. The encoded protein is the major protein of gap junctions in the heart that are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. A related intronless pseudogene has been mapped to chromosome 5. Mutations in this gene have been associated with oculodentodigital dysplasia, autosomal recessive craniometaphyseal dysplasia and heart malformations. [provided by RefSeq, May 2014]
    Orthologs
    Location:
    6q22.31
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 6 NC_000006.12 (121435577..121449744)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (121756745..121770873)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein S15a pseudogene 21 Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 29 Neighboring gene RNA, U4 small nuclear 35, pseudogene Neighboring gene transcription factor A, mitochondrial pseudogene

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Alopecia congenita keratosis palmoplantaris
    MedGen: C1863093 OMIM: 104100 GeneReviews: Not available
    Compare labs
    Atrioventricular septal defect and common atrioventricular junction
    MedGen: C0344783 OMIM: 600309 GeneReviews: Not available
    Compare labs
    Craniometaphyseal dysplasia, autosomal recessive type
    MedGen: C1857496 OMIM: 218400 GeneReviews: Not available
    Compare labs
    Erythrokeratodermia variabilis
    MedGen: C0265961 OMIM: 133200 GeneReviews: Not available
    Compare labs
    Hypoplastic left heart syndrome
    MedGen: C0152101 OMIM: 241550 GeneReviews: Not available
    Compare labs
    Oculodentodigital dysplasia
    MedGen: C0812437 OMIM: 164200 GeneReviews: Not available
    Compare labs
    Oculodentodigital dysplasia, autosomal recessive
    MedGen: C2749477 OMIM: 257850 GeneReviews: Not available
    Compare labs
    Syndactyly type 3
    MedGen: C1861366 OMIM: 186100 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated (2013-11-20)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated (2013-11-20)

    ClinGen Genome Curation Page

    NHGRI GWAS Catalog

    Description
    A genome-wide association study identifies protein quantitative trait loci (pQTLs).
    NHGRI GWA Catalog
    Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.
    NHGRI GWA Catalog
    Genome-wide association analysis identifies multiple loci related to resting heart rate.
    NHGRI GWA Catalog
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
    NHGRI GWA Catalog
    • Arrhythmogenic Right Ventricular Cardiomyopathy, organism-specific biosystem (from WikiPathways)
      Arrhythmogenic Right Ventricular Cardiomyopathy, organism-specific biosystemAdapted from KEGG: http://www.genome.jp/kegg/pathway/hsa/hsa05412.html
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Calcium Regulation in the Cardiac Cell, organism-specific biosystem (from WikiPathways)
      Calcium Regulation in the Cardiac Cell, organism-specific biosystemCalcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory affects on many enzymes and proteins. Calcium can act in signal transduction after influx resu...
    • Corticotropin-releasing hormone signaling pathway, organism-specific biosystem (from WikiPathways)
      Corticotropin-releasing hormone signaling pathway, organism-specific biosystemCorticotropin-releasing hormone (CRH) is a neuropeptide secreted abundantly in the paraventricular nucleus of the hypothalamus, amygdala, cerebral cortex and cerebellum in the central nervous system ...
    • EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
      EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
    • Formation of annular gap junctions, organism-specific biosystem (from REACTOME)
      Formation of annular gap junctions, organism-specific biosystemGap junction plaque internalization and the disruption cell communication requires a reorganization of Cx molecular interactions. Proteins including Dab-2, AP-2, Dynamin and Myosin VI associate w...
    • Gap junction, organism-specific biosystem (from KEGG)
      Gap junction, organism-specific biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...
    • Gap junction, conserved biosystem (from KEGG)
      Gap junction, conserved biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...
    • Gap junction assembly, organism-specific biosystem (from REACTOME)
      Gap junction assembly, organism-specific biosystemThe assembly of gap junctions involves (1) synthesis of connexin polypeptides at endoplasmic reticulum membranes, (2) oligomerization into homomeric- and heteromeric gap junction connexons (hemi-chan...
    • Gap junction degradation, organism-specific biosystem (from REACTOME)
      Gap junction degradation, organism-specific biosystemThe half-life of Cx is very short (1 to 5h) compared to other junctional proteins (Laird et al., 1995 ; Fallon and Goudenough, 1981). Connexins are targeted for degradation by the proteasome and the...
    • Gap junction trafficking, organism-specific biosystem (from REACTOME)
      Gap junction trafficking, organism-specific biosystemGap junctions are intercellular communication channels formed from Cx (connexin) protein subunits (see Segretain and Falk 2004 and Evans et al. 2006 for comprehensive reviews). Connexins are transpor...
    • Gap junction trafficking and regulation, organism-specific biosystem (from REACTOME)
      Gap junction trafficking and regulation, organism-specific biosystemGap junctions are clusters of intercellular channels connecting adjacent cells and permitting the direct exchange of ions and small molecules between cells. These channels are composed of two hemicha...
    • Membrane Trafficking, organism-specific biosystem (from REACTOME)
      Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
    • Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane, organism-specific biosystem (from REACTOME)
      Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane, organism-specific biosystemThrough videomicroscopy, a saltatory transport of connexon vesicles along curvilinear microtubules from the Golgi to the plasma membrane has been observed (Lauf et al., 2002). Such a transport system...
    • Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
      Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
    • N-cadherin signaling events, organism-specific biosystem (from Pathway Interaction Database)
      N-cadherin signaling events, organism-specific biosystem
      N-cadherin signaling events
    • Oligomerization of connexins into connexons, organism-specific biosystem (from REACTOME)
      Oligomerization of connexins into connexons, organism-specific biosystemThe mechanism of connexin assembly into connexons has been well characterized. Two different types of connexons can be formed. A connexon containing six identical connexin molecules is referred to as...
    • Regulation of gap junction activity, organism-specific biosystem (from REACTOME)
      Regulation of gap junction activity, organism-specific biosystemSrc is believed to suppress gap junction communication by phosphorylating Cx43.
    • Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
      Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
    • Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
      Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
    • TarBasePathway, organism-specific biosystem (from WikiPathways)
      TarBasePathway, organism-specific biosystemThis cataloge pathway was created using the database from "http://diana.cslab.ece.ntua.gr/tarbase/" with exclusions based on evidance type. This pathway only incldes miR targeted genes expressed in A...
    • Transport of connexins along the secretory pathway, organism-specific biosystem (from REACTOME)
      Transport of connexins along the secretory pathway, organism-specific biosystemConnexins follow the classical secretory transport route from the ER to the plasma membrane: ER -> ERGIC -> Golgi -> TGN (Trans Golgi Network) -> PM (Plasma Membrane). All connexins assemble or oli...
    • Transport of connexons to the plasma membrane, organism-specific biosystem (from REACTOME)
      Transport of connexons to the plasma membrane, organism-specific biosystemFollowing connexon oligomerization, the hemichannels must be transported to the plasma membrane. This has been shown to occur in transport vesicles called "cargo containers". Most of post-Golgi carg...
    • Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem (from Pathway Interaction Database)
      Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem
      Validated transcriptional targets of AP1 family members Fra1 and Fra2
    • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
      Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...
    • Wnt Signaling Pathway Netpath, organism-specific biosystem (from WikiPathways)
      Wnt Signaling Pathway Netpath, organism-specific biosystemWNT signal, through the canonical pathway, controls cell fate determination and through the non-canonical pathway controls cell movement and tissue polarity. The name "wnt" is a fusion of two terms, ...
    • c-src mediated regulation of Cx43 function and closure of gap junctions, organism-specific biosystem (from REACTOME)
      c-src mediated regulation of Cx43 function and closure of gap junctions, organism-specific biosystemThe kinases c-Src (Giepmans et al. 2001; Sorgen et al. 2004), PKc (Lin et al. 2003) and MAPK (Mograbi et al. 2003) play an essential role in the phosphorylation of Cx which leads to its degradation. ...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    PDZ domain binding IEA
    Inferred from Electronic Annotation
    more info
     
    SH3 domain binding IEA
    Inferred from Electronic Annotation
    more info
     
    connexin binding IEA
    Inferred from Electronic Annotation
    more info
     
    disordered domain specific binding IEA
    Inferred from Electronic Annotation
    more info
     
    gap junction channel activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    gap junction channel activity involved in cardiac conduction electrical coupling NAS
    Non-traceable Author Statement
    more info
    PubMed 
    gap junction channel activity involved in cell communication by electrical coupling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    ion transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    signal transducer activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    signal transducer activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    ATP transport IEA
    Inferred from Electronic Annotation
    more info
     
    apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    atrial cardiac muscle cell action potential TAS
    Traceable Author Statement
    more info
    PubMed 
    cell communication by electrical coupling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell communication by electrical coupling involved in cardiac conduction NAS
    Non-traceable Author Statement
    more info
    PubMed 
    cell-cell signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to mechanical stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    chronic inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    decidualization IEA
    Inferred from Electronic Annotation
    more info
     
    endothelium development IEA
    Inferred from Electronic Annotation
    more info
     
    epididymis development IEA
    Inferred from Electronic Annotation
    more info
     
    gap junction assembly TAS
    Traceable Author Statement
    more info
    PubMed 
    heart development IEA
    Inferred from Electronic Annotation
    more info
     
    ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    muscle contraction TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of DNA biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of cardiac muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of cell growth ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of endothelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of wound healing IEA
    Inferred from Electronic Annotation
    more info
     
    neuron projection morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of I-kappaB kinase/NF-kappaB signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of behavioral fear response IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of blood vessel diameter IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of cell communication by chemical coupling IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of cytosolic calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of glomerular filtration IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of vasoconstriction IEA
    Inferred from Electronic Annotation
    more info
     
    protein oligomerization IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of bicellular tight junction assembly IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of calcium ion transport IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of transmembrane transporter activity IEA
    Inferred from Electronic Annotation
    more info
     
    response to fluid shear stress IEA
    Inferred from Electronic Annotation
    more info
     
    response to glucose IEA
    Inferred from Electronic Annotation
    more info
     
    response to ischemia IEA
    Inferred from Electronic Annotation
    more info
     
    response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    response to pH IEA
    Inferred from Electronic Annotation
    more info
     
    response to peptide hormone IEA
    Inferred from Electronic Annotation
    more info
     
    response to retinoic acid IEA
    Inferred from Electronic Annotation
    more info
     
    signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transport TAS
    Traceable Author Statement
    more info
    PubMed 
    vascular transport IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    Golgi apparatus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Golgi membrane TAS
    Traceable Author Statement
    more info
     
    Golgi-associated vesicle membrane TAS
    Traceable Author Statement
    more info
     
    connexin complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    early endosome IEA
    Inferred from Electronic Annotation
    more info
     
    endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    fascia adherens IEA
    Inferred from Electronic Annotation
    more info
     
    focal adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    gap junction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    gap junction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    integral component of plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    intercalated disc IDA
    Inferred from Direct Assay
    more info
    PubMed 
    intercalated disc ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    lysosome IEA
    Inferred from Electronic Annotation
    more info
     
    membrane raft ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    mitochondrial outer membrane IEA
    Inferred from Electronic Annotation
    more info
     
    mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    multivesicular body IEA
    Inferred from Electronic Annotation
    more info
     
    plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    gap junction alpha-1 protein
    Names
    connexin-43
    gap junction 43 kDa heart protein
    gap junction protein, alpha 1, 43kDa

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008308.1 RefSeqGene

      Range
      4979..19146
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000165.4NP_000156.1  gap junction alpha-1 protein

      See identical proteins and their annotated locations for NP_000156.1

      Status: REVIEWED

      Source sequence(s)
      AL139098, AW664595, BC026329, BP226987
      Consensus CDS
      CCDS5123.1
      UniProtKB/Swiss-Prot
      P17302
      Related
      ENSP00000282561.3, OTTHUMP00000017111, ENST00000282561.3, OTTHUMT00000042023
      Conserved Domains (4) summary
      smart00037
      Location:4376
      CNX; Connexin homologues
      smart01089
      Location:165231
      Connexin_CCC; Gap junction channel protein cysteine-rich domain
      pfam00029
      Location:3233
      Connexin; Connexin
      pfam03508
      Location:293312
      Connexin43; Gap junction alpha-1 protein (Cx43)

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p7 Primary Assembly

      Range
      121435577..121449744
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018917.2 Alternate CHM1_1.1

      Range
      122020528..122034696
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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