GJA5 gap junction protein, alpha 5, 40kDa [Homo sapiens (human)] - Gene

Summary

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Official Symbol: GJA5provided by HGNC
Official Full Name: gap junction protein, alpha 5, 40kDaprovided by HGNC
Primary source: HGNC:4279
See related: Ensembl:ENSG00000143140; HPRD:08699; MIM:121013
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: CX40; ATFB11
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. Mutations in this gene may be associated with atrial fibrillation. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 1q21.1

Sequence :: Chromosome: 1; NC_000001.10 (147228332..147245484, complement)

See GJA5 in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Genotyping of rs10465885 showed that the patients with early-onset lone AF were more likely to carry the A allele compared with controls (odds ratio = 1.30; P = 0.011).
Title: Rare variants in GJA5 are associated with early-onset lone atrial fibrillation.
Cx40 coding SNPs are uncommon in atrial fibrillation populations, although rare mutations in this gene may lead to atrial fibrillation pathogenesis.
Title: Low prevalence of connexin-40 gene variants in atrial tissues and blood from atrial fibrillation subjects.
Results implicate GJA5 as the gene responsible for the congenital heart disease phenotypes observed with copy number imbalances at this locus.
Title: Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls.
our study could not detect an association of Cx40 promoter polymorphisms and CAD in human
Title: Lack of association between connexin40 polymorphisms and coronary artery disease.
This is the first evidence of intrinsic differences in the Ca2+ regulatory properties of Cx43 and Cx40.
Title: Gating of connexin 43 gap junctions by a cytoplasmic loop calmodulin binding domain.
Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in approximately 50% of cells; well-defined gap junctions were observed in other cells.
Title: A connexin40 mutation associated with a malignant variant of progressive familial heart block type I.
Regulation of endothelial connexin40 expression by shear stress via PI3K/Akt pathway.
Title: Regulation of endothelial connexin40 expression by shear stress.
Association between hereditary sick sinus node syndrome and connexin 40 gene polymorphism was demonstrated.
Title: [Polymorphism of connexin 40 gene-- a novel genetic marker of the sick sinus node syndrome].
Study shows that fusion of a V5/6-His tag (hexa moiety M r = 0.93 kDa) to the CT segment of Cx40, Cx43 and Cx45 does not prevent the cells from forming channels.
Title: Influence of v5/6-His tag on the properties of gap junction channels composed of connexin43, connexin40 or connexin45.
There is an alternate promoter polymorphism that directly affects levels of Cx40 mRNA in vivo and is associated with early-onset lone atrial fibrillation.
Title: A common connexin-40 gene promoter variant affects connexin-40 expression in human atria and is associated with atrial fibrillation.

Submit: New GeneRIF Correction See all (33)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Atrial fibrillation, familial, 11

MIM: 614049

Genetic Testing Registry

NHGRI GWAS Catalog

Common genetic variation and performance on standardized cognitive tests.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P36382	Q9Y312	AAR2	HPRD	PubMed
P36382	P17302	GJA1	HPRD	PubMed
P36382	P17612	PRKACA	HPRD	PubMed
BioGRID:108969	BioGRID:117464	AAR2	BioGRID	PubMed	Two-hybrid
BioGRID:108969	BioGRID:108964	GJA1	BioGRID	PubMed	Co-purification
BioGRID:108969	BioGRID:110309	MARK1	BioGRID	PubMed	Two-hybrid
BioGRID:108969	BioGRID:115127	RIMS3	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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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...
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 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...

General gene information

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Markers

RH71190 (e-PCR)
- UniSTS:46870

RH69491 (e-PCR)
- UniSTS:70844

Genotypes

See GJA5 SNP Geneview Report
See GJA5 SNP Genotype Report
See GJA5 SNP Variation Viewer Report

Homology

Homologs of the GJA5 gene: The GJA5 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling	IDA Inferred from Direct Assay more info
gap junction channel activity involved in cardiac conduction electrical coupling	IDA Inferred from Direct Assay more info
gap junction channel activity involved in cardiac conduction electrical coupling	IMP Inferred from Mutant Phenotype more info	PubMed
gap junction hemi-channel activity	IDA Inferred from Direct Assay more info

Process	Evidence Code	Pubs
AV node cell to bundle of His cell communication by electrical coupling	IMP Inferred from Mutant Phenotype more info
angiogenesis	IEP Inferred from Expression Pattern more info	PubMed
artery morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
atrial septum development	IMP Inferred from Mutant Phenotype more info
atrial septum morphogenesis	IEA Inferred from Electronic Annotation more info
atrial ventricular junction remodeling	IEA Inferred from Electronic Annotation more info
bundle of His cell to Purkinje myocyte communication	IMP Inferred from Mutant Phenotype more info
cardiac conduction system development	IEA Inferred from Electronic Annotation more info
cell communication by electrical coupling involved in cardiac conduction	IDA Inferred from Direct Assay more info	PubMed
embryonic heart tube development	IEA Inferred from Electronic Annotation more info
embryonic limb morphogenesis	IEA Inferred from Electronic Annotation more info
foramen ovale closure	IEA Inferred from Electronic Annotation more info
gap junction assembly	IDA Inferred from Direct Assay more info
gap junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
mitral valve development	IMP Inferred from Mutant Phenotype more info
outflow tract morphogenesis	IMP Inferred from Mutant Phenotype more info
pulmonary valve formation	IMP Inferred from Mutant Phenotype more info
regulation of SA node cell action potential	IEA Inferred from Electronic Annotation more info
regulation of atrial cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info
regulation of atrial cardiac muscle cell membrane depolarization	IMP Inferred from Mutant Phenotype more info
regulation of cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of heart rate by cardiac conduction	IEA Inferred from Electronic Annotation more info
regulation of membrane depolarization involved in regulation of cardiac muscle cell action potential	IEA Inferred from Electronic Annotation more info
regulation of renin secretion into blood stream	IEA Inferred from Electronic Annotation more info
regulation of vasodilation	IEA Inferred from Electronic Annotation more info
regulation of ventricular cardiac muscle cell action potential	IEA Inferred from Electronic Annotation more info
regulation of ventricular cardiac muscle cell membrane depolarization	IEA Inferred from Electronic Annotation more info
regulation of ventricular cardiac muscle cell membrane repolarization	IEA Inferred from Electronic Annotation more info
renal system process involved in regulation of systemic arterial blood pressure	IEA Inferred from Electronic Annotation more info
septum primum development	IEA Inferred from Electronic Annotation more info
skeletal system development	IEA Inferred from Electronic Annotation more info
ventricular septum development	IMP Inferred from Mutant Phenotype more info
ventricular septum morphogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
connexon complex	IDA Inferred from Direct Assay more info
gap junction	IDA Inferred from Direct Assay more info
integral to plasma membrane	IDA Inferred from Direct Assay more info
intercalated disc	IDA Inferred from Direct Assay more info	PubMed
intercalated disc	TAS Traceable Author Statement more info

General protein information

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Preferred Names: gap junction alpha-5 protein

Names: gap junction alpha-5 protein; connexin 40; connexin-40

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.

Genomic

NG_009369.1 RefSeqGene

Range

5001..22153

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005266.5 → NP_005257.2 gap junction alpha-5 protein

Status: REVIEWED

Description

Transcript Variant: This variant (A) represents the longer transcript. Variants A and B encode the same protein.

Source sequence(s)

AL365260

Consensus CDS

CCDS929.1

UniProtKB/Swiss-Prot

P36382

Related

ENSP00000271348, ENST00000271348

Conserved Domains (2) summary

pfam00029
Location:3 – 109
Blast Score: 573

Connexin; Connexin

pfam10582
Location:163 – 211
Blast Score: 237

Connexin_CCC; Gap junction channel protein cysteine-rich domain
NM_181703.2 → NP_859054.1 gap junction alpha-5 protein

Status: REVIEWED

Description

Transcript Variant: This variant (B) differs in the 5' UTR compared to variant A. Variants A and B encode the same protein.

Source sequence(s)

AL365260, BC013313

Consensus CDS

CCDS929.1

UniProtKB/Swiss-Prot

P36382

Conserved Domains (2) summary

pfam00029
Location:3 – 109
Blast Score: 573

Connexin; Connexin

pfam10582
Location:163 – 211
Blast Score: 237

Connexin_CCC; Gap junction channel protein cysteine-rich domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 PATCHES

Genomic

NW_003871055.2 Reference GRCh37.p10 PATCHES

Range

4496704..4513885, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

147228332..147245484, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

120641850..120659015, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

154229656..154246837, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01004402.1 (88591..105756)	None
genomic	AC241644.1 (42948..60129)	None
genomic	AF151979.1	AAD37801.1
genomic	AL365260.11	CAI14124.1
		CAI14125.1
genomic	AMYH01001373.1 (2365610..2382791)	None
genomic	CH471223.1	EAW50929.1
		EAW50930.1
genomic	L34954.1	AAA91833.1
genomic	U03486.2	AAA60457.2
mRNA	AF074995.1	None
mRNA	BC013313.2	AAH13313.1
mRNA	BQ231177.1	None
mRNA	BT019415.1	AAV38222.1
mRNA	BT019416.1	AAV38223.1
other-genetic	DQ891889.2	ABM82815.1
other-genetic	DQ895075.2	ABM86001.1