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GJA1 Gene

protein-coding   GIFtS: 71
GCID: GC06P121756

Gap Junction Protein, Alpha 1, 43kDa

(Previous names: gap junction protein, alpha-like, gap junction protein,...)
(Previous symbols: ODDD, GJAL)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Gap Junction Protein, Alpha 1, 43kDa1 2     Gap Junction Protein, Alpha 1, 43kDa (Connexin 43)1
GJAL1 2 3     Gap Junction Protein, Alpha-Like1
ODDD1 2 5     Oculodentodigital Dysplasia (Syndactyly Type III)1
Connexin 431 2     DFNB382
Gap Junction 43 KDa Heart Protein2 3     connexin-432
AVSD32 5     Gap Junction Alpha-1 Protein2
CMDR2 5     Connexin-433
CX432 5     Cx433
HLHS12 5     ODOD5
HSS2 5     SDTY35

External Ids:    HGNC: 42741   Entrez Gene: 26972   Ensembl: ENSG000001526617   OMIM: 1210145   UniProtKB: P173023   

Export aliases for GJA1 gene to outside databases

Previous GC identifers: GC06P121527 GC06P121714 GC06P121737 GC06P121798 GC06P119340


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for GJA1 Gene:
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 and heart malformations. (provided by RefSeq, Jul 2008)

GeneCards Summary for GJA1 Gene:
GJA1 (gap junction protein, alpha 1, 43kDa) is a protein-coding gene. Diseases associated with GJA1 include syndactyly, and oculodentodigital dysplasia, autosomal recessive. GO annotations related to this gene include SH3 domain binding and receptor binding. An important paralog of this gene is GJB3.

UniProtKB/Swiss-Prot: CXA1_HUMAN, P17302
Function: Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster
of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from
one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the
recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by
enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic
neural stimuli and causing them to contract (By similarity)

summary for GJA1 Gene:
Gap channels (also known as gap junctions) are specalized cell-cell contacts between almost all eukaryotic
cells that provide direct intracellular communication. Generally, gap channels allow the passive diffusion
of molecules up to 1 kDa which includes nutrients, small metabolites (e.g. glucose), ions (K+, Ca2+) and
second messengers (IP3, cAMP and cGMP). Gap channels allow electrical and biochemical coupling between cells
and in excitable tissues, such as neurons and the heart, enables the generation of synchronized and rapid
responses. Structurally, gap channels are composed of two hemichannels called 'connexons', which themselves
are formed from six connexin molecules. Homo- and heteromeric combinations are seen, which exhibit distinct
permeability, selectivity and functional properties. Pannexins are related to connexins and can also form
gap junctions. However, their expression is limited to the brain. Furthermore, in nonchordate animals a
family of proteins called innexins form these channels. Gap channels are regulated through
post-translational modifications of the C'-terminal cytoplasmic tail and phosphorylation modulates assembly
and their physiological properties. They are continuously synthesized and degraded, allowing tissues to
rapidly adapt to changing environmental conditions. Connexins play a key role in many physiological
processes including cardiac and smooth muscle contraction, regulation of neuronal excitability, epithelial
electrolyte transport and keratinocyte differentiation. Mutations in connexin genes are associated with
human diseases including sensorineural deafness, a variety of skin disorders, peripheral neuropathy and
cardiovascular disease.

Gene Wiki entry for GJA1 (Gap junction protein, alpha 1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000006.12  NC_018917.2  NT_025741.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the GJA1 gene promoter:
         PPAR-gamma1   Sp1   COMP1   Cart-1   MyoD   CUTL1   PPAR-gamma2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidGJA1 promoter sequence
   Search Chromatin IP Primers for GJA1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GJA1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6q22.31   Ensembl cytogenetic band:  6q22.31   HGNC cytogenetic band: 6q22.31

GJA1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GJA1 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06P121756:  view genomic region     (about GC identifiers)

Start:
121,756,745 bp from pter      End:
121,770,873 bp from pter
Size:
14,129 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: CXA1_HUMAN, P17302 (See protein sequence)
Recommended Name: Gap junction alpha-1 protein  
Size: 382 amino acids; 43008 Da
Subunit: A connexon is composed of a hexamer of connexins. Interacts (via C-terminus) with TJP1. Interacts (via
C-terminus) with SRC (via SH3 domain). Interacts with UBQLN4 (By similarity). Interacts with SGSM3. Interacts
with KIAA1432/CIP150. Interacts with CNST and CSNK1D
Caution: PubMed:7715640 reported a mutation Pro-364 linked to congenital heart diseases. PubMed:8873667 later
shown that it is an artifact
Caution: PubMed:11741837 reported 2 mutations (Phe-11 and Ala-24) linked to non-syndromic autosomal recessive
deafness (DFNBG). These mutations have subsequently been shown (PubMed:12457340) to involve the pseudogene of
connexin-43 located on chromosome 5
1 PDB 3D structure from and Proteopedia for GJA1:
2LL2 (3D)    
Secondary accessions: B2R5U9 Q6FHU1 Q9Y5I8

Explore the universe of human proteins at neXtProt for GJA1: NX_P17302

Explore proteomics data for GJA1 at MOPED

Post-translational modifications: 

  • Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of
    gap junction activity (By similarity). Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap
    junction assembly1
  • Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the level of functional Cx43 gap junctions at the
    plasma membrane. May be desumoylated by SENP1 or SENP21
  • S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel
    permeability and may regulate of smooth muscle cell to endothelial cell communication1
  • Ubiquitination2 at Lys9, Lys303
  • Modification sites at PhosphoSitePlus

  • See GJA1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_000156.1  
    ENSEMBL proteins: 
     ENSP00000282561  
    Reactome Protein details: P17302

    GJA1 Human Recombinant Protein Products:

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    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    GJA1 Antibody Products:

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    R&D Systems Antibodies for GJA1 (Connexin 43/GJA1)
    Cell Signaling Technology (CST) Antibodies for GJA1  (Cx43)
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    GJA1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    GJ: Ion channels / Gap junction proteins (connexins)

    IUPHAR Guide to PHARMACOLOGY protein family classification: Cx43
    Connexins and Pannexins

    Selected InterPro protein domains (see all 6):
     IPR000500 Connexin
     IPR013124 Connexin43_C
     IPR019570 Connexin_CCC
     IPR013092 Connexin_N
     IPR002261 Connexin43

    Graphical View of Domain Structure for InterPro Entry P17302

    ProtoNet protein and cluster: P17302

    3 Blocks protein domains:
    IPB002261 Gap junction alpha-1 protein (Cx43) signature
    IPB013092 Connexin
    IPB013124 Gap junction alpha-1 protein (Cx43)


    UniProtKB/Swiss-Prot: CXA1_HUMAN, P17302
    Similarity: Belongs to the connexin family. Alpha-type (group II) subfamily


    GJA1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CXA1_HUMAN, P17302
    Function: Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster
    of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from
    one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the
    recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by
    enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic
    neural stimuli and causing them to contract (By similarity)

         Genatlas biochemistry entry for GJA1:
    gap junction protein,alpha 1,43kDa,connexin 43),expressed in the heart left ventricule,liver,peripheral nervous
    system,monomer of the connexon (six subunits),underexpressed in breast cancer cell (marker for detecting early
    oncogenesis in the breast)

         Gene Ontology (GO): Selected molecular function terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004871signal transducer activity IMP12761501
    GO:0005102receptor binding ----
    GO:0005243gap junction channel activity IDA16790700
    GO:0005515protein binding IPI15709751
    GO:0015075ion transmembrane transporter activity TAS1696265
         
    GJA1 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for GJA1:
     Decreased focal adhesion (FA)   Stronger migration 

         Selected MGI mutant phenotypes (inferred from 25 alleles(MGI details for Gja1) (see all 23):
     behavior/neurological  cardiovascular system  cellular  craniofacial  embryogenesis 
     endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  mortality/aging  muscle 

    GJA1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for GJA1: Gja1tm1.1Kwi Gja1tm1Kdr Gja1tm1.1Gfi

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for GJA1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for GJA1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for GJA1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for GJA1

    miRNA
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    miRTarBase miRNAs that target GJA1:
    hsa-mir-206 (MIRT021080), hsa-mir-23b-3p (MIRT046296), hsa-mir-1 (MIRT001984), hsa-mir-342-3p (MIRT043680)

    Block miRNA regulation of human, mouse, rat GJA1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate GJA1 (see all 36):
    hsa-miR-582-3p hsa-miR-607 hsa-miR-624* hsa-miR-301a hsa-miR-30d hsa-miR-342-3p hsa-miR-30a hsa-miR-23a
    SwitchGear 3'UTR luciferase reporter plasmidGJA1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat GJA1

    Gene Editing
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    GenScript: all cDNA clones in your preferred vector: GJA1 (NM_000165)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat GJA1

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GJA1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CXA1_HUMAN, P17302: Cell membrane; Multi-pass membrane protein. Cell junction, gap junction
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    endoplasmic reticulum4
    golgi apparatus4
    cytoskeleton3
    extracellular3
    endosome2
    lysosome2
    mitochondrion2
    nucleus2
    vacuole2
    cytosol1

    Gene Ontology (GO): Selected cellular component terms (see all 24):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005737cytoplasm ----
    GO:0005741mitochondrial outer membrane IEA--
    GO:0005764lysosome IEA--
    GO:0005768endosome ----

    GJA1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for GJA1 About   (see all 21)  
    See pathways by source

    SuperPathContained pathways About
    1Hypertrophic cardiomyopathy (HCM)
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)0.54
    Arrhythmogenic right ventricular cardiomyopathy0.54
    2Signaling in Gap Junctions
    Gap junction0.31
    Signaling in Gap Junctions0.31
    3Gap junction trafficking
    Gap junction trafficking0.93
    Gap junction degradation0.00
    Gap junction trafficking and regulation0.93
    Gap junction assembly0.00
    Formation of annular gap junctions0.00
    4Oligomerization of connexins into connexons
    Oligomerization of connexins into connexons
    Transport of connexons to the plasma membrane0.00
    Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane0.00
    Transport of connexins along the secretory pathway0.00
    5Myometrial Relaxation and Contraction Pathways
    Myometrial Relaxation and Contraction Pathways0.43
    Calcium Regulation in the Cardiac Cell0.43

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for GJA1
        Signaling in Gap Junctions

    2 Cell Signaling Technology (CST) Pathways for GJA1
        Cytoskeletal Signaling
    Adhesion

    2 GeneGo (Thomson Reuters) Pathways for GJA1
        Cell adhesion Endothelial cell contacts by junctional mechanisms
    Cell adhesion Gap junctions

    Selected BioSystems Pathways for GJA1 (see all 9)
        Myometrial Relaxation and Contraction Pathways
    EGFR1 Signaling Pathway
    SIDS Susceptibility Pathways
    Calcium Regulation in the Cardiac Cell
    Spinal Cord Injury


    Selected Reactome Pathways for GJA1 (see all 7)
        Gap junction degradation
    Gap junction assembly
    c-src mediated regulation of Cx43 function and closure of gap junctions
    Formation of annular gap junctions
    Transport of connexins along the secretory pathway

    1 PharmGKB Pathway for GJA1
        Antiarrhythmic Pathway, Pharmacodynamics

    2 Kegg Pathways  (Kegg details for GJA1):
        Gap junction
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)


    GJA1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including GJA1 (see all 7): 
              WNT Signaling Targets in human mouse rat
              PI3K-AKT Signaling Pathway in human mouse rat
              Cell Junction PathwayFinder in human mouse rat
              Huntington's Disease in human mouse rat
              Gap Junctions in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for GJA1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for GJA1 (P173021, 2, 3 ENSP000002825614) via UniProtKB, MINT, STRING, and/or I2D (see all 110)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TJP1Q071571, 2, 3, ENSP000002815374EBI-1103439,EBI-79553 MINT-3088474 MINT-1791009 MINT-1791038 I2D: score=5 STRING: ENSP00000281537
    SRCP129312, 3, ENSP000003509414MINT-8026668 I2D: score=4 STRING: ENSP00000350941
    CAV1Q031353, ENSP000003391914I2D: score=3 STRING: ENSP00000339191
    CSNK1DP487303, ENSP000003244644I2D: score=3 STRING: ENSP00000324464
    MAPK7Q131643, ENSP000003110054I2D: score=3 STRING: ENSP00000311005
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 56):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001649osteoblast differentiation ----
    GO:0001701in utero embryonic development ----
    GO:0001764neuron migration ----
    GO:0001947heart looping ----
    GO:0002070epithelial cell maturation ----

    GJA1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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       Browse drugs & compounds from Enzo Life Sciences
    5 ApexBio Compounds for GJA1     About this table
    CompoundAction CAS #
    10PanxPanx-1 mimetic inhibitory peptide, blocks pannexin-1 gap junctions[955091-53-9]
    Gap 26Gap junction blocker peptide, mapping to connexin 43 residue 63-75[197250-15-0]
    Gap 27Gap junction blocker peptide[198284-64-9]
    GAP-134 Hydrochloridealter conduction pathways and promote cardiac re-entry mechanisms[943134-39-2]
    Scrambled 10PanxPanx-1 mimetic inhibitory peptide, blocks pannexin-1 gap junctions[1315378-72-3]

    Compounds for GJA1 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    Gap 27Selective gap junction blocker[198284-64-9]
    Scrambled 10Panx Scrambled version of 10Panx (Cat. No. 3348), Panx-1 mimetic inhibitory peptide [1315378-72-3]
    Carbenoxolone disodiumGap junction blocker. Also inhibitor of 11 beta-hydroxysteroid dehydrogenase[7421-40-1]
    10PanxPanx-1 mimetic inhibitory peptide; blocks pannexin-1 gap junctions[955091-53-9]

    1 DrugBank Compound for GJA1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Carvedilol-- 72956-09-3targetother16448880 16563290

    4 IUPHAR Ligands for GJA1 (Cx43)    About this table
    LigandTypeActionAffinityPubmed IDs
    flufenamic acid
    InhibitorNone--
    octanol
    InhibitorNone--
    Ca2+
    InhibitorNone--
    carbenoxolone
    InhibitorNone--

    Selected Novoseek inferred chemical compound relationships for GJA1 gene (see all 117)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    oddd 93.1 72 18269311 (6), 17420259 (4), 16219735 (3), 16418219 (3) (see all 23)
    connexin 45 82.7 25 9693379 (6), 14678136 (3), 7877871 (2), 15094345 (2) (see all 9)
    18alpha-glycyrrhetinic acid 82.4 9 10362727 (2), 11880266 (1), 12509912 (1), 20512937 (1) (see all 7)
    heptanol 68.7 1 11716536 (1)
    connexin 42 67.6 3 8204908 (1), 7818094 (1)
    glycyrrhetinic acid 63.6 2 12651152 (1), 16328273 (1)
    carbenoxolone 61.4 5 15843434 (1), 20406988 (1), 15987459 (1), 18837047 (1) (see all 5)
    oleamide 58.2 3 17570214 (1), 10207896 (1)
    cx38 57.7 2 9598590 (1), 12456713 (1)
    ganciclovir 52.1 12 15891776 (2), 8700844 (1), 9930323 (1), 11769669 (1) (see all 8)



    GJA1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for GJA1 gene: 
    NM_000165.3  

    Unigene Cluster for GJA1:

    Gap junction protein, alpha 1, 43kDa
    Hs.74471  [show with all ESTs]
    Unigene Representative Sequence: NM_000165
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000282561(uc011ebo.1 uc011ebp.1 uc003pyr.3)
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Selected qRT-PCR Assays for microRNAs that regulate GJA1 (see all 36):
    hsa-miR-582-3p hsa-miR-607 hsa-miR-624* hsa-miR-301a hsa-miR-30d hsa-miR-342-3p hsa-miR-30a hsa-miR-23a
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    Additional mRNA sequence: 

    AK223289.1 AK294670.1 AK295460.1 AK297402.1 AK297761.1 AK297764.1 AK309377.1 AK309490.1 
    AK312324.1 AK316159.1 BC026329.1 CR541660.1 M65188.1 X52947.1 

    13 DOTS entries:

    DT.75164162  DT.100823493  DT.100761073  DT.92456426  DT.100696819  DT.95231061  DT.102833081  DT.121394848 
    DT.121394850  DT.121394936  DT.92456424  DT.121394931  DT.95231049 

    Selected AceView cDNA sequences (see all 391):

    BG679966 CD676363 BQ188571 AI827381 AV709013 CB269430 C00380 AU121200 
    BM722776 CB116451 BU740247 AA137270 AI873718 X52947 CA413943 AI683417 
    AU147058 AA339604 AA629753 CR593006 BG678754 AA629916 AU125425 CA389632 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    GJA1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TGTTCTGGAG
    GJA1 Expression
    About this image


    GJA1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 36) fully expand
     
     Heart (Cardiovascular System)    fully expand to see all 8 entries
             Ventricular Conductive Cells Fast Conducting System
             Encapsulated Embryoid Bodies
     
     Eye (Sensory Organs)    fully expand to see all 9 entries
             Adult Corneal Superbasal Epithelial Cells Corneal Epithelium
             Optic cup
     
     Epithelial Cells
             Adult Corneal Superbasal Epithelial Cells Corneal Epithelium
     
     Neural Crest (Gastrulation Derivatives)    fully expand to see all 3 entries
             Neural Crest Outflow Tract Cells Outflow Tract
     
     Lateral Plate Mesoderm (Gastrulation Derivatives)    fully expand to see all 2 entries
             Proepicardial Progenitor cells Proepicardium
    GJA1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    GJA1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.74471

    UniProtKB/Swiss-Prot: CXA1_HUMAN, P17302
    Tissue specificity: Expressed in the heart and fetal cochlea

        Pathway & Disease-focused RT2 Profiler PCR Arrays including GJA1 (see all 7): 
              WNT Signaling Targets in human mouse rat
              PI3K-AKT Signaling Pathway in human mouse rat
              Cell Junction PathwayFinder in human mouse rat
              Huntington's Disease in human mouse rat
              Gap Junctions in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for GJA1 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Gja11 , 5 gap junction protein, alpha 11, 5 88.22(n)1
    97.38(a)1
      10 (28.64 cM)5
    146091  NM_010288.31  NP_034418.11 
     563773005 
    chicken
    (Gallus gallus)
    Aves GJA11 gap junction protein, alpha 1, 43kDa 82.15(n)
    93.7(a)
      395278  NM_204586.2  NP_989917.1 
    lizard
    (Anolis carolinensis)
    Reptilia GJA16
    gap junction protein, alpha 1, 43kDa
    86(a)
    1 ↔ 1
    1(182897779-182898927)
    African clawed frog
    (Xenopus laevis)
    Amphibia gja1-A2 gap junction protein, alpha 1, 43kDa 77.27(n)    X17243.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cx432 connexin 43 75.63(n)   30236  AF035481.1 


    ENSEMBL Gene Tree for GJA1 (if available)
    TreeFam Gene Tree for GJA1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for GJA1 gene
    GJB32  GJA102  GJD32  GJB62  GJB42  GJB22  GJB72  GJA42  
    GJC12  GJB52  GJC22  GJA52  GJD22  GJA32  GJA92  GJA82  
    GJB12  
    16 SIMAP similar genes for GJA1 using alignment to 1 protein entry:     CXA1_HUMAN:
    GJA8    GJA10    GJB1    GJB2    GJA4    GJA5
    GJA9    GJB6    GJD2    GJB4    GJB7    GJC1
    GJA3    GJB5    GJB3    GJD3

    GJA1 for paralogs           About GeneDecksing


    2 Pseudogenes.org Pseudogenes for GJA1
    PGOHUM00000251326 PGOHUM00000241658


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for GJA1 (see all 405)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs289316011,2,,4
    COculodentodigital dysplasia (ODDD)4 pathogenic1121770118(+) CTCATA/GTGTTC 2 M V mis1 ese30--------
    rs289316001,2,,4
    CSyndactyly 3 (SDTY3)4 pathogenic1121770259(+) AGCATA/GGTAAG 2 S G mis10--------
    rs22278851,2,,4
    C,FHypoplastic left heart syndrome 1 (HLHS1)4 pathogenic1121770917(+) CCAGCG/AACCTT 2 /Q /R mis11Minor allele frequency- A:0.43MN 44
    VAR_0589994
    Oculodentodigital dysplasia (ODDD)4--see VAR_0589992 V A mis40--------
    VAR_0383564
    Oculodentodigital dysplasia (ODDD)4--see VAR_0383562 S P mis40--------
    VAR_0590084
    Oculodentodigital dysplasia (ODDD)4--see VAR_0590082 H P mis40--------
    VAR_0590064
    Oculodentodigital dysplasia (ODDD)4--see VAR_0590062 T N mis40--------
    VAR_0157614
    Oculodentodigital dysplasia (ODDD)4--see VAR_0157612 G R mis40--------
    VAR_0589964
    Oculodentodigital dysplasia (ODDD)4--see VAR_0589962 P H mis40--------
    VAR_0590054
    Oculodentodigital dysplasia (ODDD)4--see VAR_0590052 T A mis40--------

    HapMap Linkage Disequilibrium report for GJA1 (121756745 - 121770873 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for GJA1: --
    Human Gene Mutation Database (HGMD): GJA1
    Locus Specific Mutation Databases (LSDB): GJA1

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 121014   
    OMIM disorders: 164200  186100  241550  600309  257850  218400  
    UniProtKB/Swiss-Prot: CXA1_HUMAN, P17302
  • Oculodentodigital dysplasia (ODDD) [MIM:164200]: A disease characterized by a typical facial appearance
    and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow,
    pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow
    nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small
    and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation
    is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved
    and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances. Note=The
    disease is caused by mutations affecting the gene represented in this entry
  • Oculodentodigital dysplasia, autosomal recessive (ODDD-AR) [MIM:257850]: A disease characterized by a
    typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial
    features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares
    together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The
    teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The
    characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III)
    but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are
    observed in rare instances. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Syndactyly 3 (SDTY3) [MIM:186100]: A form of syndactyly, a congenital anomaly of the hand or foot marked
    by persistence of the webbing between adjacent digits that are more or less completely attached. In SDTY3, there
    is usually complete and bilateral syndactyly between the fourth and fifth fingers. Usually it is soft tissue
    syndactyly but occasionally the distal phalanges are fused. The fifth finger is short with absent or rudimentary
    middle phalanx. The feet are not affected. Note=The disease may be caused by mutations affecting the gene
    represented in this entry
  • Hypoplastic left heart syndrome 1 (HLHS1) [MIM:241550]: A syndrome due to defective development of the
    aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve.
    As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium,
    right ventricle, and pulmonary artery are enlarged. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Hallermann-Streiff syndrome (HSS) [MIM:234100]: A disorder characterized by a typical skull shape
    (brachycephaly with frontal bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, skin
    atrophy, dental anomalies and proportionate short stature. Mental retardation is present in a minority of cases.
    Note=The disease is caused by mutations affecting the gene represented in this entry
  • Atrioventricular septal defect 3 (AVSD3) [MIM:600309]: A congenital heart malformation characterized by a
    common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves
    underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve
    itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by
    separate atrioventricular valvar orifices despite a common junction. Note=The disease is caused by mutations
    affecting the gene represented in this entry
  • Craniometaphyseal dysplasia, autosomal recessive (CMDR) [MIM:218400]: An osteochondrodysplasia
    characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the
    metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve
    compression, that may finally result in hearing loss and facial palsy. Note=The disease is caused by mutations
    affecting the gene represented in this entry

  • Selected diseases for GJA1 (see all 136):    
    About MalaCards
    syndactyly    oculodentodigital dysplasia, autosomal recessive    syndactyly type 3    mitral atresia
    oculodentodigital dysplasia    criss-cross heart    hallermann-streiff syndrome    hypoplastic left heart syndrome 1
    atrioventricular septal defect 3    brain glioma    hypoplastic left heart syndrome    craniometaphyseal dysplasia
    microphthalmia cataract    basaloid squamous cell carcinoma    keratosis follicularis    dental enamel hypoplasia
    axenfeld-rieger syndrome    skin atrophy    diabetic foot ulcers    atrioventricular septal defect

    6 diseases from the University of Copenhagen DISEASES database for GJA1:
    Heart disease     Syndactyly     Vascular disease     Hallermann-Streiff syndrome
    Cancer     Dental enamel hypoplasia

    GJA1 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for GJA1 gene (see all 94)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    oculodentodigital dysplasia 93.1 49 12457340 (3), 15637728 (2), 16219735 (2), 15644317 (2) (see all 21)
    oculodentodigital dysplasia syndrome 78.8 2 16410543 (1), 19847613 (1)
    syndactyly 54.3 2 15637728 (1), 19439426 (1)
    keratoderma palmoplantar 49.7 2 15551259 (2)
    arrhythmia 48.6 17 18201716 (2), 12448696 (1), 15495803 (1), 16690883 (1) (see all 16)
    glioma 47 72 9989416 (5), 20074329 (4), 11180621 (3), 18004727 (3) (see all 28)
    neoplastic transformation 46.4 7 7495228 (1), 11142098 (1), 15194214 (1), 12635093 (1) (see all 6)
    glioblastoma 36.7 28 12019157 (3), 11279616 (3), 9823317 (3), 11746825 (3) (see all 14)
    acantholysis 36.1 1 10468792 (1)
    tumors 33.8 173 15567553 (6), 15642212 (5), 14519646 (4), 1324944 (3) (see all 77)

    Genetic Association Database (GAD): GJA1
    Human Genome Epidemiology (HuGE) Navigator: GJA1 (17 documents)

    Export disorders for GJA1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for GJA1 gene, integrated from 10 sources (see all 1034):
    (articles sorted by number of sources associating them with GJA1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The human connexin gene family of gap junction proteins: distinct chromosomal locations but similar structures. (PubMed id 1646158)1, 2, 3, 9 Fishman G.I.... Leinwand L.A. (Genomics 1991)
    2. Mutations of connexin43 in fetuses with congenital heart malformations. (PubMed id 15978203)1, 2, 4, 9 Chen P.... Chang C. (Chin. Med. J. 2005)
    3. Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness. (PubMed id 11741837)1, 2, 4, 9 Liu X.Z....Nance W.E. (Hum. Mol. Genet. 2001)
    4. Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE). (PubMed id 11470490)1, 2, 4 Dasgupta C....Fletcher W.H. (Mutat. Res. 2001)
    5. Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. (PubMed id 12457340)1, 2, 9 Paznekas W.A....Jabs E.W. (Am. J. Hum. Genet. 2003)
    6. A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype. (PubMed id 14974090)1, 2, 9 Pizzuti A....Dallapiccola B. (Hum. Mutat. 2004)
    7. Intercellular calcium signaling via gap junction in connexin-43- transfected cells. (PubMed id 9430691)1, 2, 9 Toyofuku T.... Tada M. (J. Biol. Chem. 1998)
    8. A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features. (PubMed id 18161618)1, 2, 9 de la Parra D.R. and Zenteno J.C. (Ophthalmic Genet. 2007)
    9. A novel mutation in the GJA1 gene in a family with oculodentodigital dysplasia. (PubMed id 16219735)1, 2, 9 Vasconcellos J.P.C.... Costa V.P. (Arch. Ophthalmol. 2005)
    10. Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates DNA synthesis in cell-cell contact forming cardiomyocytes. (PubMed id 14702389)1, 2, 9 Doble B.W.... Kardami E. (J. Cell Sci. 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2697 HGNC: 4274 AceView: GJA1 Ensembl:ENSG00000152661 euGenes: HUgn2697
    ECgene: GJA1 Kegg: 2697 H-InvDB: GJA1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for GJA1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for GJA1 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=GJA1[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for GJA1 gene:
    Search GeneIP for patents involving GJA1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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