• Gene id: 2697

Gene Summary

• Gene Symbol: GJA1   Gene   UCSC   Ensembl
• Aliases: AVSD3, CMDR, CX43, EKVP, EKVP3, GJAL, HLHS1, HSS, ODDD, PPKCA
• Gene name: gap junction protein alpha 1
• Alternate names: gap junction alpha-1 protein, connexin-43, gap junction 43 kDa heart protein, gap junction protein, alpha 1, 43kDa,
• Gene location: 6q22.31 (121435576: 121449743)     Exons: 2     NC_000006.12
• Gene summary(Entrez): 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
• OMIM: 121014

Protein Summary

• Protein general information: P17302  
  • Name: Gap junction alpha 1 protein (Connexin 43) (Cx43) (Gap junction 43 kDa heart protein)
  • Length: 382  
  • Mass: 43,008
• Sequence:

  MGDWSALGKLLDKVQAYSTAGGKVWLSVLFIFRILLLGTAVESAWGDEQSAFRCNTQQPGCENVCYDKSFPISHV
  RFWVLQIIFVSVPTLLYLAHVFYVMRKEEKLNKKEEELKVAQTDGVNVDMHLKQIEIKKFKYGIEEHGKVKMRGG
  LLRTYIISILFKSIFEVAFLLIQWYIYGFSLSAVYTCKRDPCPHQVDCFLSRPTEKTIFIIFMLVVSLVSLALNI
  IELFYVFFKGVKDRVKGKSDPYHATSGALSPAKDCGSQKYAYFNGCSSPTAPLSPMSPPGYKLVTGDRNNSSCRN
  YNKQASEQNWANYSAEQNRMGQAGSTISNSHAQPFDFPDDNQNSKKLAAGHELQPLAIVDQRPSSRASSRASSRP
  RPDDLEI

• Structural information:
  • Interpro: IPR035091  IPR000500  IPR002261  IPR013124  IPR034634   IPR019570  IPR017990  IPR013092  IPR038359  
  • Prosite: PS00407 PS00408
  • PDB: 2LL2
  • PDBsum: 2LL2
  • STRING: ENSP00000282561
• Other Databases: GeneCards:  GJA1  Malacards:  GJA1

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0000139	Golgi membrane	TAS	cellular component
GO:0001649	osteoblast differentiation	IEA	biological process
GO:0001701	in utero embryonic development	IEA	biological process
GO:0001764	neuron migration	IEA	biological process
GO:0001937	negative regulation of endothelial cell proliferation	IEA	biological process
GO:0001947	heart looping	IEA	biological process
GO:0002027	regulation of heart rate	IEA	biological process
GO:0002070	epithelial cell maturation	IEA	biological process
GO:0002088	lens development in camera-type eye	IEA	biological process
GO:0002544	chronic inflammatory response	IEA	biological process
GO:0003104	positive regulation of glomerular filtration	IEA	biological process
GO:0003158	endothelium development	IEA	biological process
GO:0003294	atrial ventricular junction remodeling	IEA	biological process
GO:0004871	signal transducer activity	IMP	molecular function
GO:0004871	signal transducer activity	IDA	molecular function
GO:0005102	receptor binding	IEA	molecular function
GO:0005243	gap junction channel activity	IDA	molecular function
GO:0005243	gap junction channel activity	IDA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005739	mitochondrion	IDA	cellular component
GO:0005741	mitochondrial outer membrane	IEA	cellular component
GO:0005764	lysosome	IEA	cellular component
GO:0005769	early endosome	IEA	cellular component
GO:0005771	multivesicular body	IEA	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005794	Golgi apparatus	ISS	cellular component
GO:0005829	cytosol	IEA	cellular component
GO:0005882	intermediate filament	IEA	cellular component
GO:0005886	plasma membrane	ISS	cellular component
GO:0005886	plasma membrane	ISS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005887	integral component of plasma membrane	TAS	cellular component
GO:0005916	fascia adherens	IEA	cellular component
GO:0005921	gap junction	ISS	cellular component
GO:0005921	gap junction	IDA	cellular component
GO:0005921	gap junction	IDA	cellular component
GO:0005922	connexin complex	IEA	cellular component
GO:0005925	focal adhesion	IDA	cellular component
GO:0006810	transport	TAS	biological process
GO:0006915	apoptotic process	IEA	biological process
GO:0006936	muscle contraction	TAS	biological process
GO:0007165	signal transduction	IDA	biological process
GO:0007204	positive regulation of cytosolic calcium ion concentration	IEA	biological process
GO:0007267	cell-cell signaling	IDA	biological process
GO:0007507	heart development	TAS	biological process
GO:0007512	adult heart development	IEA	biological process
GO:0009268	response to pH	IEA	biological process
GO:0009749	response to glucose	IEA	biological process
GO:0010232	vascular transport	IEA	biological process
GO:0010628	positive regulation of gene expression	IEA	biological process
GO:0010629	negative regulation of gene expression	IEA	biological process
GO:0010643	cell communication by chemical coupling	IEA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010652	positive regulation of cell communication by chemical coupling	IEA	biological process
GO:0014704	intercalated disc	ISS	cellular component
GO:0014704	intercalated disc	IDA	cellular component
GO:0014704	intercalated disc	IDA	cellular component
GO:0015075	ion transmembrane transporter activity	IDA	molecular function
GO:0015867	ATP transport	IEA	biological process
GO:0016264	gap junction assembly	TAS	biological process
GO:0016264	gap junction assembly	TAS	biological process
GO:0016324	apical plasma membrane	IEA	cellular component
GO:0016328	lateral plasma membrane	IEA	cellular component
GO:0017124	SH3 domain binding	IEA	molecular function
GO:0030165	PDZ domain binding	IEA	molecular function
GO:0030308	negative regulation of cell growth	ISS	biological process
GO:0030500	regulation of bone mineralization	IEA	biological process
GO:0030660	Golgi-associated vesicle membrane	TAS	cellular component
GO:0030660	Golgi-associated vesicle membrane	TAS	cellular component
GO:0032024	positive regulation of insulin secretion	IEA	biological process
GO:0034220	ion transmembrane transport	IDA	biological process
GO:0034405	response to fluid shear stress	IEA	biological process
GO:0042733	embryonic digit morphogenesis	IEA	biological process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	biological process
GO:0043292	contractile fiber	IEA	cellular component
GO:0043403	skeletal muscle tissue regeneration	IEA	biological process
GO:0043434	response to peptide hormone	IEA	biological process
GO:0045121	membrane raft	ISS	cellular component
GO:0045669	positive regulation of osteoblast differentiation	IEA	biological process
GO:0045732	positive regulation of protein catabolic process	IEA	biological process
GO:0045844	positive regulation of striated muscle tissue development	IEA	biological process
GO:0045907	positive regulation of vasoconstriction	IEA	biological process
GO:0045909	positive regulation of vasodilation	IEA	biological process
GO:0046850	regulation of bone remodeling	IEA	biological process
GO:0048487	beta-tubulin binding	IEA	molecular function
GO:0048514	blood vessel morphogenesis	IEA	biological process
GO:0048812	neuron projection morphogenesis	IEA	biological process
GO:0051259	protein oligomerization	IEA	biological process
GO:0051924	regulation of calcium ion transport	IEA	biological process
GO:0060044	negative regulation of cardiac muscle cell proliferation	IEA	biological process
GO:0060156	milk ejection reflex	IEA	biological process
GO:0060307	regulation of ventricular cardiac muscle cell membrane repolarization	IEA	biological process
GO:0060371	regulation of atrial cardiac muscle cell membrane depolarization	IEA	biological process
GO:0060373	regulation of ventricular cardiac muscle cell membrane depolarization	IEA	biological process
GO:0061045	negative regulation of wound healing	IEA	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0071253	connexin binding	IEA	molecular function
GO:0071260	cellular response to mechanical stimulus	IEA	biological process
GO:0086014	atrial cardiac muscle cell action potential	TAS	biological process
GO:0086064	cell communication by electrical coupling involved in cardiac conduction	NAS	biological process
GO:0086075	gap junction channel activity involved in cardiac conduction electrical coupling	NAS	molecular function
GO:0097110	scaffold protein binding	IEA	molecular function
GO:1903763	gap junction channel activity involved in cell communication by electrical coupling	IDA	molecular function
GO:2000279	negative regulation of DNA biosynthetic process	IEA	biological process
GO:2000810	regulation of bicellular tight junction assembly	IEA	biological process
GO:2000987	positive regulation of behavioral fear response	IEA	biological process
GO:0000139	Golgi membrane	TAS	cellular component
GO:0001649	osteoblast differentiation	IEA	biological process
GO:0001701	in utero embryonic development	IEA	biological process
GO:0001764	neuron migration	IEA	biological process
GO:0001937	negative regulation of endothelial cell proliferation	IEA	biological process
GO:0001947	heart looping	IEA	biological process
GO:0002027	regulation of heart rate	IEA	biological process
GO:0002070	epithelial cell maturation	IEA	biological process
GO:0002088	lens development in camera-type eye	IEA	biological process
GO:0002544	chronic inflammatory response	IEA	biological process
GO:0003104	positive regulation of glomerular filtration	IEA	biological process
GO:0003158	endothelium development	IEA	biological process
GO:0003294	atrial ventricular junction remodeling	IEA	biological process
GO:0004871	signal transducer activity	IMP	molecular function
GO:0004871	signal transducer activity	IDA	molecular function
GO:0005102	receptor binding	IEA	molecular function
GO:0005243	gap junction channel activity	IEA	molecular function
GO:0005243	gap junction channel activity	IDA	molecular function
GO:0005243	gap junction channel activity	IDA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005737	cytoplasm	IEA	cellular component
GO:0005739	mitochondrion	IDA	cellular component
GO:0005741	mitochondrial outer membrane	IEA	cellular component
GO:0005764	lysosome	IEA	cellular component
GO:0005768	endosome	IEA	cellular component
GO:0005769	early endosome	IEA	cellular component
GO:0005770	late endosome	IEA	cellular component
GO:0005771	multivesicular body	IEA	cellular component
GO:0005783	endoplasmic reticulum	IEA	cellular component
GO:0005783	endoplasmic reticulum	IEA	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005794	Golgi apparatus	IEA	cellular component
GO:0005794	Golgi apparatus	ISS	cellular component
GO:0005829	cytosol	IEA	cellular component
GO:0005882	intermediate filament	IEA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	ISS	cellular component
GO:0005886	plasma membrane	ISS	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005887	integral component of plasma membrane	TAS	cellular component
GO:0005911	cell-cell junction	IEA	cellular component
GO:0005916	fascia adherens	IEA	cellular component
GO:0005921	gap junction	IEA	cellular component
GO:0005921	gap junction	ISS	cellular component
GO:0005921	gap junction	IEA	cellular component
GO:0005921	gap junction	IEA	cellular component
GO:0005921	gap junction	IDA	cellular component
GO:0005921	gap junction	IDA	cellular component
GO:0005922	connexin complex	IEA	cellular component
GO:0005922	connexin complex	IEA	cellular component
GO:0005922	connexin complex	TAS	cellular component
GO:0005925	focal adhesion	IDA	cellular component
GO:0006810	transport	TAS	biological process
GO:0006915	apoptotic process	IEA	biological process
GO:0006936	muscle contraction	TAS	biological process
GO:0007154	cell communication	IEA	biological process
GO:0007154	cell communication	IEA	biological process
GO:0007165	signal transduction	IDA	biological process
GO:0007204	positive regulation of cytosolic calcium ion concentration	IEA	biological process
GO:0007267	cell-cell signaling	IEA	biological process
GO:0007267	cell-cell signaling	IEA	biological process
GO:0007267	cell-cell signaling	IDA	biological process
GO:0007267	cell-cell signaling	TAS	biological process
GO:0007507	heart development	IEA	biological process
GO:0007507	heart development	IEA	biological process
GO:0007507	heart development	TAS	biological process
GO:0007512	adult heart development	IEA	biological process
GO:0008016	regulation of heart contraction	IEA	biological process
GO:0008285	negative regulation of cell proliferation	IEA	biological process
GO:0009268	response to pH	IEA	biological process
GO:0009749	response to glucose	IEA	biological process
GO:0010232	vascular transport	IEA	biological process
GO:0010628	positive regulation of gene expression	IEA	biological process
GO:0010629	negative regulation of gene expression	IEA	biological process
GO:0010643	cell communication by chemical coupling	IEA	biological process
GO:0010644	cell communication by electrical coupling	IEA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010652	positive regulation of cell communication by chemical coupling	IEA	biological process
GO:0014704	intercalated disc	IEA	cellular component
GO:0014704	intercalated disc	ISS	cellular component
GO:0014704	intercalated disc	IDA	cellular component
GO:0014704	intercalated disc	IDA	cellular component
GO:0015075	ion transmembrane transporter activity	IDA	molecular function
GO:0015867	ATP transport	IEA	biological process
GO:0016020	membrane	IEA	cellular component
GO:0016020	membrane	IEA	cellular component
GO:0016021	integral component of membrane	IEA	cellular component
GO:0016264	gap junction assembly	TAS	biological process
GO:0016264	gap junction assembly	TAS	biological process
GO:0016324	apical plasma membrane	IEA	cellular component
GO:0016328	lateral plasma membrane	IEA	cellular component
GO:0017124	SH3 domain binding	IEA	molecular function
GO:0019904	protein domain specific binding	IEA	molecular function
GO:0022857	transmembrane transporter activity	IEA	molecular function
GO:0030054	cell junction	IEA	cellular component
GO:0030054	cell junction	IEA	cellular component
GO:0030165	PDZ domain binding	IEA	molecular function
GO:0030308	negative regulation of cell growth	IEA	biological process
GO:0030308	negative regulation of cell growth	ISS	biological process
GO:0030500	regulation of bone mineralization	IEA	biological process
GO:0030660	Golgi-associated vesicle membrane	TAS	cellular component
GO:0030660	Golgi-associated vesicle membrane	TAS	cellular component
GO:0032024	positive regulation of insulin secretion	IEA	biological process
GO:0034220	ion transmembrane transport	IDA	biological process
GO:0034405	response to fluid shear stress	IEA	biological process
GO:0035050	embryonic heart tube development	IEA	biological process
GO:0042733	embryonic digit morphogenesis	IEA	biological process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	biological process
GO:0043292	contractile fiber	IEA	cellular component
GO:0043403	skeletal muscle tissue regeneration	IEA	biological process
GO:0043434	response to peptide hormone	IEA	biological process
GO:0045121	membrane raft	IEA	cellular component
GO:0045121	membrane raft	ISS	cellular component
GO:0045216	cell-cell junction organization	IEA	biological process
GO:0045669	positive regulation of osteoblast differentiation	IEA	biological process
GO:0045732	positive regulation of protein catabolic process	IEA	biological process
GO:0045844	positive regulation of striated muscle tissue development	IEA	biological process
GO:0045907	positive regulation of vasoconstriction	IEA	biological process
GO:0045909	positive regulation of vasodilation	IEA	biological process
GO:0046850	regulation of bone remodeling	IEA	biological process
GO:0048487	beta-tubulin binding	IEA	molecular function
GO:0048514	blood vessel morphogenesis	IEA	biological process
GO:0048812	neuron projection morphogenesis	IEA	biological process
GO:0051259	protein oligomerization	IEA	biological process
GO:0051924	regulation of calcium ion transport	IEA	biological process
GO:0055085	transmembrane transport	IEA	biological process
GO:0060044	negative regulation of cardiac muscle cell proliferation	IEA	biological process
GO:0060156	milk ejection reflex	IEA	biological process
GO:0060307	regulation of ventricular cardiac muscle cell membrane repolarization	IEA	biological process
GO:0060371	regulation of atrial cardiac muscle cell membrane depolarization	IEA	biological process
GO:0060373	regulation of ventricular cardiac muscle cell membrane depolarization	IEA	biological process
GO:0061045	negative regulation of wound healing	IEA	biological process
GO:0061337	cardiac conduction	IEA	biological process
GO:0070062	extracellular exosome	IDA	cellular component
GO:0071253	connexin binding	IEA	molecular function
GO:0071260	cellular response to mechanical stimulus	IEA	biological process
GO:0086014	atrial cardiac muscle cell action potential	TAS	biological process
GO:0086064	cell communication by electrical coupling involved in cardiac conduction	NAS	biological process
GO:0086075	gap junction channel activity involved in cardiac conduction electrical coupling	NAS	molecular function
GO:0097110	scaffold protein binding	IEA	molecular function
GO:1903763	gap junction channel activity involved in cell communication by electrical coupling	IDA	molecular function
GO:2000279	negative regulation of DNA biosynthetic process	IEA	biological process
GO:2000810	regulation of bicellular tight junction assembly	IEA	biological process
GO:2000987	positive regulation of behavioral fear response	IEA	biological process
GO:0000139	Golgi membrane	TAS	cellular component
GO:0004871	signal transducer activity	IMP	molecular function
GO:0004871	signal transducer activity	IDA	molecular function
GO:0005243	gap junction channel activity	IDA	molecular function
GO:0005243	gap junction channel activity	IDA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005739	mitochondrion	IDA	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005794	Golgi apparatus	ISS	cellular component
GO:0005886	plasma membrane	ISS	cellular component
GO:0005886	plasma membrane	ISS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0005887	integral component of plasma membrane	TAS	cellular component
GO:0005921	gap junction	ISS	cellular component
GO:0005921	gap junction	IDA	cellular component
GO:0005921	gap junction	IDA	cellular component
GO:0005922	connexin complex	TAS	cellular component
GO:0005925	focal adhesion	IDA	cellular component
GO:0006810	transport	TAS	biological process
GO:0006936	muscle contraction	TAS	biological process
GO:0007165	signal transduction	IDA	biological process
GO:0007267	cell-cell signaling	IDA	biological process
GO:0007267	cell-cell signaling	TAS	biological process
GO:0007507	heart development	TAS	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0010644	cell communication by electrical coupling	IDA	biological process
GO:0014704	intercalated disc	ISS	cellular component
GO:0014704	intercalated disc	IDA	cellular component
GO:0014704	intercalated disc	IDA	cellular component
GO:0015075	ion transmembrane transporter activity	IDA	molecular function
GO:0016264	gap junction assembly	TAS	biological process
GO:0016264	gap junction assembly	TAS	biological process
GO:0030308	negative regulation of cell growth	ISS	biological process
GO:0030660	Golgi-associated vesicle membrane	TAS	cellular component
GO:0030660	Golgi-associated vesicle membrane	TAS	cellular component
GO:0034220	ion transmembrane transport	IDA	biological process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	biological process
GO:0045121	membrane raft	ISS	cellular component
GO:0070062	extracellular exosome	IDA	cellular component
GO:0086014	atrial cardiac muscle cell action potential	TAS	biological process
GO:0086064	cell communication by electrical coupling involved in cardiac conduction	NAS	biological process
GO:0086075	gap junction channel activity involved in cardiac conduction electrical coupling	NAS	molecular function
GO:1903763	gap junction channel activity involved in cell communication by electrical coupling	IDA	molecular function

KEGG pathways

Pathway id	Pathway name
hsa04540	Gap junction
hsa05412	Arrhythmogenic right ventricular cardiomyopathy

Diseases

Associated diseases	References
Cardiovascular disease	GAD: 15978203
Hypoplastic left heart syndrome	OMIM: 121014
Atrioventricular septal defect	KEGG: H00547
Erythrokeratodermia variabilis et progressiva	OMIM: 121014
Cleft defects	GAD: 20634891
Craniometaphyseal dysplasia	OMIM: 121014
Syndactyly	KEGG: H01095
Febrile seizures	GAD: 19854014
Hearing Loss	GAD: 19027966
Non-syndromic deafness	GAD: 11741837
Schizophrenia	GAD: 20347265
Presbycusis	GAD: 18988928
Adenomyosis	INFBASE: 21176558
Endometriosis	INFBASE: 24270393
Azoospermia	MIK: 12649345
Male factor infertility	MIK: 22611165
Primary seminiferous tubule failure	MIK: 23706332
Male factor infertility	MIK: 12649345
Palmoplantar keratoderma	OMIM: 121014
Oculodentodigital dysplasia	OMIM: 121014
Associated with impaired spermatogenesis	MIK: 10555545
Associated with male infertility	MIK: 20655897
Associated with spermatogenesis and epigenetic regulation	MIK: 21674046
Azoospermia	MIK: 12649345
Hypospermatogenesis	MIK: 28361989
Primary seminiferous tubule failure	MIK: 23706332
Required for maintanence of spermatogenesis	MIK: 27281705
Male infertility	MIK: 27281705
Required for normal testicular development and spermatogenesis	MIK: 17591950

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
23706332	Primary seminiferous tubule failure			16 (6 with meiotic arrest, 7 with the Sertoli cell-only phenotype, 3 with normal spermatogenesis)	Male infertiltiy
12649345	Azoospermia				Male infertiltiy
22611165	Azoospermia			16 (6 histologically normal epididymal tubule from men with localized testis cancer with active spermatogenesis, 6 histologically normal epididymal tubule from patients with NOA, secondary to Sertoli-cell only syndrome, 4 Epididymal tubule from men with n	Male infertility	GJA1 (Cx43) GJB1 (Cx32) and GJB2 (Cx26)
20655897	Associated with male infertility				Male infertility
17591950	Required for normal testicular development and spermatogenesis				Male infertility
10555545	Assocaited with impaired spermatogenesis				Male infertility
27281705	Required for maintanence of spermatogenesis, Male infertility				Male infertility
21674046	Associated with spermatogenesis and epigenetic regulation			18	Male infertility	GSE26881
28361989	Hypospermatogenesis			6 (3 controls, 3 Klienfelter syndrome	Male infertility	Microarray