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

Gene ID: 2697, updated on 20-Jan-2019

Summary

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
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; EKVP3; 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]
Expression
Broad expression in skin (RPKM 198.8), adrenal (RPKM 176.9) and 17 other tissues See more
Orthologs

Genomic context

See GJA1 in Genome Data Viewer
Location:
6q22.31
Exon count:
2
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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

Genomic regions, transcripts, and products

Expression

  • 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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Alopecia congenita keratosis palmoplantaris
MedGen: C3151468 OMIM: 104100 GeneReviews: Not available
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Atrioventricular septal defect and common atrioventricular junction
MedGen: C3275750 OMIM: 600309 GeneReviews: Not available
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Craniometaphyseal dysplasia, autosomal recessive type
MedGen: C2931244 OMIM: 218400 GeneReviews: Not available
Compare labs
Erythrokeratodermia variabilis et progressiva 3
MedGen: C4479619 OMIM: 617525 GeneReviews: Not available
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Hypoplastic left heart syndrome 1
MedGen: C4551854 OMIM: 241550 GeneReviews: Not available
not available
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

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat upregulates the expression of GJA1 (Cx43) by binding the promoter of Cx43 in human astrocytes PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • 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. ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
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 
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 cell growth ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of I-kappaB kinase/NF-kappaB signaling HMP PubMed 
positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
spermatogenesis ISS
Inferred from Sequence or Structural Similarity
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
 
apical plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
cell junction IDA
Inferred from Direct Assay
more info
PubMed 
connexin complex ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
focal adhesion HDA 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
 
intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
 
membrane raft ISS
Inferred from Sequence or Structural Similarity
more info
 
mitochondrion IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
gap junction alpha-1 protein
Names
connexin-43
gap junction 43 kDa heart protein
gap junction protein, alpha 1, 43kDa

NCBI Reference Sequences (RefSeq)

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
    5048..19129
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000165.5NP_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
    ENSP00000497788.1, ENST00000649132.1
    Conserved Domains (2) summary
    pfam00029
    Location:3233
    Connexin; Connexin
    pfam03508
    Location:293312
    Connexin43; Gap junction alpha-1 protein (Cx43)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p12 Primary Assembly

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