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

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; AllianceGenome:HGNC:4274
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: mouse all
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Genomic context

Location:: 6q22.31

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (121435646..121449727)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (122622700..122636781)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (121756792..121770873)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mutations of the Cx43 Gene in Non-Small Cell Lung Cancer: Association with Aberrant Localization of Cx43 Protein Expression and Tumor Progression.
Title: Mutations of the Cx43 Gene in Non-Small Cell Lung Cancer: Association with Aberrant Localization of Cx43 Protein Expression and Tumor Progression.
Endothelial-adipocyte Cx43 Mediated Gap Junctions Can Regulate Adiposity.
Title: Endothelial-adipocyte Cx43 Mediated Gap Junctions Can Regulate Adiposity.
Connexin 43 controls metastatic behavior in triple negative breast cancer through TGFbeta1-Smad3-intergin alphaV signaling axis Based on optical image diagnosis.
Title: Connexin 43 controls metastatic behavior in triple negative breast cancer through TGFβ1-Smad3-intergin αV signaling axis Based on optical image diagnosis.
Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes.
Title: Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes.
Connexin 43 Modulation in Human Chondrocytes, Osteoblasts and Cartilage Explants: Implications for Inflammatory Joint Disorders.
Title: Connexin 43 Modulation in Human Chondrocytes, Osteoblasts and Cartilage Explants: Implications for Inflammatory Joint Disorders.
Human coronavirus OC43 infection remodels connexin 43-mediated gap junction intercellular communication in vitro.
Title: Human coronavirus OC43 infection remodels connexin 43-mediated gap junction intercellular communication in vitro.
NGF increases Connexin-43 expression and function in pulmonary arterial smooth muscle cells to induce pulmonary artery hyperreactivity.
Title: NGF increases Connexin-43 expression and function in pulmonary arterial smooth muscle cells to induce pulmonary artery hyperreactivity.
The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation.
Title: The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation.
KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.
Title: KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.
Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.
Title: Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.

Submit: New GeneRIF Correction See all GeneRIFs (639)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal dominant palmoplantar keratoderma and congenital alopecia MedGen: C4304669 OMIM: 104100 GeneReviews: Not available	Compare labs
Craniometaphyseal dysplasia, autosomal recessive MedGen: C2931244 OMIM: 218400 GeneReviews: Not available	Compare labs
Erythrokeratodermia variabilis et progressiva 3 MedGen: C4479619 OMIM: 617525 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

EBI GWAS Catalog

Description
A genome-wide association study identifies protein quantitative trait loci (pQTLs). EBI GWAS Catalog EBI GWAS CatalogPubMed
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. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies multiple loci related to resting heart rate. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC170950P8 (e-PCR)
- UniSTS:271626

RH27497 (e-PCR)
- UniSTS:90137

PMC151788P1 (e-PCR)
- UniSTS:271174

WI-6988 (e-PCR)
- UniSTS:20556

GJA1 (e-PCR)
- UniSTS:479912

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables alpha-tubulin binding	IDA Inferred from Direct Assay more info	PubMed
enables beta-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables efflux transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables gap junction channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables gap junction channel activity	IDA Inferred from Direct Assay more info	PubMed
enables gap junction channel activity involved in cardiac conduction electrical coupling	NAS Non-traceable Author Statement more info	PubMed
enables gap junction channel activity involved in cell communication by electrical coupling	IDA Inferred from Direct Assay more info	PubMed
enables gap junction hemi-channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables glutathione transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables monoatomic ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
enables tubulin binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in atrial cardiac muscle cell action potential	TAS Traceable Author Statement more info	PubMed
involved_in bone development	ISS Inferred from Sequence or Structural Similarity more info
involved_in bone remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac conduction system development	NAS Non-traceable Author Statement more info	PubMed
involved_in cell communication	IEA Inferred from Electronic Annotation more info
involved_in cell communication by electrical coupling	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell communication by electrical coupling	IDA Inferred from Direct Assay more info	PubMed
involved_in cell communication by electrical coupling involved in cardiac conduction	NAS Non-traceable Author Statement more info	PubMed
involved_in cell-cell signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-cell signaling	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amyloid-beta	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in establishment of mitotic spindle orientation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in export across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in gap junction assembly	TAS Traceable Author Statement more info	PubMed
involved_in glutamate secretion	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in glutathione transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in heart development	IBA Inferred from Biological aspect of Ancestor more info
involved_in heart development	IEA Inferred from Electronic Annotation more info
involved_in maintenance of blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed
involved_in microtubule-based transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell growth	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of gonadotropin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of trophoblast cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	HMP more info	PubMed
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of mesodermal cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of morphogenesis of an epithelium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of stem cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of vascular associated smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in xenobiotic transport	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in Golgi-associated vesicle membrane	TAS Traceable Author Statement more info
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cell junction	IDA Inferred from Direct Assay more info	PubMed
located_in cell-cell contact zone	IDA Inferred from Direct Assay more info	PubMed
part_of connexin complex	IBA Inferred from Biological aspect of Ancestor more info
part_of connexin complex	IEA Inferred from Electronic Annotation more info
part_of connexin complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed
part_of connexin complex	TAS Traceable Author Statement more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in focal adhesion	HDA more info	PubMed
located_in gap junction	IDA Inferred from Direct Assay more info	PubMed
located_in gap junction	IEA Inferred from Electronic Annotation more info
located_in gap junction	ISS Inferred from Sequence or Structural Similarity more info
located_in intercalated disc	IDA Inferred from Direct Assay more info	PubMed
located_in intercalated disc	ISS Inferred from Sequence or Structural Similarity more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in tight junction	IDA Inferred from Direct Assay more info	PubMed

General protein information

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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)

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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.