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

Summary

Official Symbol: GJA5provided by HGNC
Official Full Name: gap junction protein alpha 5provided by HGNC
Primary source: HGNC:HGNC:4279
See related: Ensembl:ENSG00000265107 MIM:121013; AllianceGenome:HGNC:4279
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]
Expression: Biased expression in placenta (RPKM 23.7), lung (RPKM 11.2) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q21.2

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (147756199..147773351, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (147034309..147051468)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (147228332..147245455, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DNMT1-mediated NR3C1 DNA methylation enables transcription activation of connexin40 and augments angiogenesis during colorectal cancer progression.
Title: DNMT1-mediated NR3C1 DNA methylation enables transcription activation of connexin40 and augments angiogenesis during colorectal cancer progression.
Association between polymorphisms in connexin 40 gene (Cx40) and risk of atrial fibrillation: a meta-analysis based on 3,452 subjects.
Title: Association between polymorphisms in connexin 40 gene (Cx40) and risk of atrial fibrillation: a meta-analysis based on 3,452 subjects.
A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes.
Title: A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes.
BIRC5, GAJ5, and lncRNA NPHP3-AS1 Are Correlated with the Development of Atrial Fibrillation-Valvular Heart Disease.
Title: BIRC5, GAJ5, and lncRNA NPHP3-AS1 Are Correlated with the Development of Atrial Fibrillation-Valvular Heart Disease.
KCNE2 rs8134775 was associated with a decreased atrial fibrillation (AF) risk in the Chinese Han population in the allele model. Minor allele T of GJA5 rs35594137 was associated with a decreased AF risk, and the minor allele G of KCNJ2 rs8079702 was associated with an increased AF risk in the recessive models. Results suggest that KCNE2, KCNJ2, and GJA5 influence the development of AF in the Chinese Han population.
Title: The research of ion channel-related gene polymorphisms with atrial fibrillation in the Chinese Han population.
Cx40 or Cx45 Gap junctions showed little changes in the extent of voltage-dependent-gating, but in both cases with a faster deactivation kinetics at high temperatures.
Title: Effects of temperature on transjunctional voltage-dependent gating kinetics in Cx45 and Cx40 gap junction channels.
By 143 days gestational age, the developing heart has the classical helical organization observed in mature mammalian tissue. This was accompanied by an increase in connexin 43 and connexin 40 expression levels, suggesting their role in the development of the ventricular conduction system and that electrical propagation across the heart is facilitated in later gestation.
Title: Ventricular myocardium development and the role of connexins in the human fetal heart.
Atrial Fibrillation (AF)-linked Cx40 mutants impair gap junction and/or hemichannel function, which may predispose the mutant carriers to AF.
Title: Functional Characterization of Novel Atrial Fibrillation-Linked GJA5 (Cx40) Mutants.
ur study describes for the first time an association of drug-resistant non-structural heart disease AF with the Cx37 1019C > T gene polymorphism. We also confirmed the association of the Cx40 - 26G > A polymorphism in patients with AF and structural disease.
Title: Differential Association of Cx37 and Cx40 Genetic Variants in Atrial Fibrillation with and without Underlying Structural Heart Disease.
This study shows that Cx37 C1019T and Cx40 A71G polymorphisms are not associated with cardioprotective role in Egyptians.
Title: Polymorphisms in Gap Junction Proteins and their Role in Predisposition of Acute Myocardial Infarction in Egyptians.

Submit: New GeneRIF Correction See all GeneRIFs (62)

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
Atrial fibrillation, familial, 11 MedGen: C3279693 OMIM: 614049 GeneReviews: Not available	not available
Atrial standstill 1 MedGen: C4551959 OMIM: 108770 GeneReviews: Not available	not available
Chromosome 1q21.1 deletion syndrome MedGen: C2675897 OMIM: 612474 GeneReviews: 1q21.1 Recurrent Microdeletion	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2012-02-23) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2012-02-23) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Common genetic variation and performance on standardized cognitive tests. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH71190 (e-PCR)
- UniSTS:46870

RH69491 (e-PCR)
- UniSTS:70844

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables connexin binding	IEA Inferred from Electronic Annotation more info
enables disordered domain specific binding	IEA Inferred from Electronic Annotation more info
enables gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling	IDA Inferred from Direct Assay more info	PubMed
enables gap junction channel activity involved in Purkinje myocyte-ventricular cardiac muscle cell electrical coupling	NAS Non-traceable Author Statement more info	PubMed
enables gap junction channel activity involved in SA node cell-atrial cardiac muscle cell electrical coupling	NAS Non-traceable Author Statement more info	PubMed
enables gap junction channel activity involved in atrial cardiac muscle cell-AV node cell electrical coupling	IBA Inferred from Biological aspect of Ancestor more info
enables gap junction channel activity involved in atrial cardiac muscle cell-AV node cell electrical coupling	IMP Inferred from Mutant Phenotype more info	PubMed
enables gap junction channel activity involved in atrial cardiac muscle cell-AV node cell electrical coupling	NAS Non-traceable Author Statement more info	PubMed
enables gap junction channel activity involved in bundle of His cell-Purkinje myocyte electrical coupling	IMP Inferred from Mutant Phenotype more info	PubMed
enables gap junction channel activity involved in bundle of His cell-Purkinje myocyte electrical coupling	ISS Inferred from Sequence or Structural Similarity more info
enables gap junction channel activity involved in cardiac conduction electrical coupling	IDA Inferred from Direct Assay more info	PubMed
enables gap junction channel activity involved in cardiac conduction electrical coupling	IMP Inferred from Mutant Phenotype more info	PubMed
enables gap junction hemi-channel activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in AV node cell to bundle of His cell communication by electrical coupling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Purkinje myocyte to ventricular cardiac muscle cell communication by electrical coupling	NAS Non-traceable Author Statement more info	PubMed
involved_in SA node cell to atrial cardiac muscle cell communication by electrical coupling	NAS Non-traceable Author Statement more info	PubMed
involved_in angiogenesis	IEP Inferred from Expression Pattern more info	PubMed
involved_in artery morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in atrial cardiac muscle cell to AV node cell communication by electrical coupling	IBA Inferred from Biological aspect of Ancestor more info
involved_in atrial cardiac muscle cell to AV node cell communication by electrical coupling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in atrial cardiac muscle cell to AV node cell communication by electrical coupling	NAS Non-traceable Author Statement more info	PubMed
involved_in atrial septum development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in bundle of His cell to Purkinje myocyte communication by electrical coupling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in bundle of His cell to Purkinje myocyte communication by electrical coupling	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within cardiac conduction system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell communication by chemical coupling	IEA Inferred from Electronic Annotation more info
involved_in cell communication by electrical coupling involved in cardiac conduction	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-cell signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in endothelium development	IEA Inferred from Electronic Annotation more info
involved_in gap junction assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in gap junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart development	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitral valve development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of blood pressure	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of glomerular filtration	IEA Inferred from Electronic Annotation more info
involved_in outflow tract morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell communication by chemical coupling	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in pulmonary valve formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of AV node cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of Purkinje myocyte action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of atrial cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of atrial cardiac muscle cell membrane depolarization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of bundle of His cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell communication by electrical coupling	IEA Inferred from Electronic Annotation more info
acts_upstream_of regulation of ventricular cardiac muscle cell membrane depolarization	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of regulation of ventricular cardiac muscle cell membrane repolarization	ISS Inferred from Sequence or Structural Similarity more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in vasodilation	IEA Inferred from Electronic Annotation more info
involved_in vasomotion	IEA Inferred from Electronic Annotation more info
involved_in ventricular septum development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell projection	IEA Inferred from Electronic Annotation more info
part_of connexin complex	IBA Inferred from Biological aspect of Ancestor more info
part_of connexin complex	IDA Inferred from Direct Assay more info	PubMed
part_of connexin complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in gap junction	IDA Inferred from Direct Assay more info	PubMed
located_in intercalated disc	IDA Inferred from Direct Assay more info	PubMed
located_in intercalated disc	TAS Traceable Author Statement more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: gap junction alpha-5 protein

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

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_009369.2 RefSeqGene

Range

17773..22176

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005266.7 → NP_005257.2 gap junction alpha-5 protein

See identical proteins and their annotated locations for NP_005257.2

Status: REVIEWED

Description

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

Source sequence(s)

AF074995, BC013313, BM970701, BQ924948, DR003194

Consensus CDS

CCDS929.1

UniProtKB/Swiss-Prot

P36382, Q5T3B6, Q5U0N6

UniProtKB/TrEMBL

A0A024QZ37, X5D2H9

Related

ENSP00000484552.1, ENST00000621517.1

Conserved Domains (2) summary

pfam00029
Location:3 → 211

Connexin

pfam16791
Location:258 → 358

Connexin40_C; Connexin 40 C-terminal domain
NM_181703.4 → NP_859054.1 gap junction alpha-5 protein

See identical proteins and their annotated locations for NP_859054.1

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)

AF074995, BC013313, BM970701, BX377692

Consensus CDS

CCDS929.1

UniProtKB/Swiss-Prot

P36382, Q5T3B6, Q5U0N6

UniProtKB/TrEMBL

A0A024QZ37, X5D2H9

Related

ENSP00000463851.1, ENST00000579774.3

Conserved Domains (2) summary

pfam00029
Location:3 → 211

Connexin

pfam16791
Location:258 → 358

Connexin40_C; Connexin 40 C-terminal domain