GJA5

gap junction protein alpha 5, the group of Gap junction proteins

Basic information

Region (hg38): 1:147756198-147773362

Links

ENSG00000265107 ∙ NCBI:2702 ∙ OMIM:121013 ∙ HGNC:4279 ∙ Uniprot:P36382 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heart conduction disease (Limited), mode of inheritance: AD
• atrial fibrillation, familial, 11 (Moderate), mode of inheritance: AD
• familial atrial fibrillation (Supportive), mode of inheritance: AD
• atrial fibrillation, familial, 11 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrial fibrillation, familial 11; Atrial standstill 1	AD/Digenic	Cardiovascular	Surveillance (eg, with echocardiography/electrocardiography) and medical/surgical intervention related to arrhythmias and associated sequelae may be beneficial	Cardiovascular	12522116; 16790700; 21076161; 22247482
For Atrial standstill, digenic inheritance (with SCN5A) has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GJA5 gene.

• Atrial standstill 1;Atrial fibrillation, familial, 11 (93 variants)
• Atrial fibrillation, familial, 11;Atrial standstill 1 (72 variants)
• not provided (29 variants)
• Atrial fibrillation, familial, 11 (25 variants)
• Familial atrial fibrillation (6 variants)
• Inborn genetic diseases (6 variants)
• not specified (1 variants)
• Atrial fibrillation, familial, 11;Chromosome 1q21.1 deletion syndrome;Atrial standstill 1 (1 variants)
• Hypertrophic cardiomyopathy (1 variants)
• Atrial standstill 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GJA5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	46	1	48
missense			113	1		114
nonsense			9			9
start loss						0
frameshift			10			10
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			11	4	3	18
Total	0	0	145	51	4

Variants in GJA5

This is a list of pathogenic ClinVar variants found in the GJA5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-147756766-C-T		Familial atrial fibrillation	Likely benign (Jun 14, 2016)
1-147756903-G-A		Familial atrial fibrillation	Uncertain significance (Jun 14, 2016)
1-147756951-T-C		Familial atrial fibrillation	Uncertain significance (Jun 14, 2016)
1-147757495-G-GGGGCATTTGCCAGAGGTACATACCA		Familial atrial fibrillation	Likely benign (Jun 14, 2016)
1-147757546-A-G		Atrial fibrillation, familial, 11	Uncertain significance (Jan 12, 2018)
1-147757554-G-A		Familial atrial fibrillation	Likely benign (Jun 14, 2016)
1-147757642-T-A		Atrial fibrillation, familial, 11	Uncertain significance (Jan 12, 2018)
1-147757654-C-T		Atrial fibrillation, familial, 11	Uncertain significance (Jan 12, 2018)
1-147757664-T-A		Atrial fibrillation, familial, 11	Uncertain significance (Jan 12, 2018)
1-147757798-G-A		Atrial fibrillation, familial, 11	Uncertain significance (Jan 12, 2018)
1-147757829-G-C		Atrial fibrillation, familial, 11	Uncertain significance (Apr 27, 2017)
1-147758102-G-A		Atrial fibrillation, familial, 11	Uncertain significance (Jan 12, 2018)
1-147758109-C-C			Benign (Aug 27, 2018)
1-147758116-A-G		Atrial fibrillation, familial, 11	Uncertain significance (Jan 13, 2018)
1-147758140-C-T		Atrial fibrillation, familial, 11	Uncertain significance (Apr 28, 2017)
1-147758168-T-A		Atrial fibrillation, familial, 11;Atrial standstill 1	Likely benign (Jun 27, 2022)
1-147758171-T-C		Atrial fibrillation, familial, 11 • Atrial standstill 1;Atrial fibrillation, familial, 11	Uncertain significance (Sep 22, 2023)
1-147758173-G-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
1-147758174-G-A		Atrial standstill 1;Atrial fibrillation, familial, 11	Likely benign (Feb 10, 2022)
1-147758174-G-T		Atrial fibrillation, familial, 11;Atrial standstill 1	Uncertain significance (Sep 15, 2023)
1-147758182-A-C		Atrial fibrillation, familial, 11	Uncertain significance (Jan 12, 2018)
1-147758193-C-T		Atrial standstill 1;Atrial fibrillation, familial, 11	Uncertain significance (Jun 15, 2023)
1-147758200-C-G		Atrial standstill 1;Atrial fibrillation, familial, 11	Uncertain significance (Jun 28, 2022)
1-147758200-CCTTA-C		Atrial standstill 1;Atrial fibrillation, familial, 11	Uncertain significance (Sep 14, 2023)
1-147758205-C-T		Atrial standstill 1;Atrial fibrillation, familial, 11	Uncertain significance (Aug 24, 2023)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
• Disease: DISEASE: Atrial standstill 1 (ATRST1) [MIM:108770]: A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm. {ECO:0000269|PubMed:16790700}. Note=The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry. A rare GJA5 genotype has been detected in combination with a mutation in SCN5A in a large family with atrial standstill.; DISEASE: Atrial fibrillation, familial, 11 (ATFB11) [MIM:614049]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:20650941}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Antiarrhythmic Pathway, Pharmacodynamics;NOTCH1 regulation of human endothelial cell calcification;Calcium Regulation in the Cardiac Cell (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.177
• rvis_EVS: -0.63
• rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

• pHI: 0.101
• hipred: N
• hipred_score: 0.441
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.517

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gja5
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; digestive/alimentary phenotype; immune system phenotype; respiratory system phenotype

Zebrafish Information Network

• Gene name: gja5b
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: dispersed

Gene ontology

• Biological process: skeletal system development;angiogenesis;negative regulation of glomerular filtration;outflow tract morphogenesis;endothelium development;cardiac conduction system development;mitral valve development;pulmonary valve formation;ventricular septum development;atrial septum development;septum primum development;atrial ventricular junction remodeling;potassium ion transport;cell communication by chemical coupling;positive regulation of cell communication by chemical coupling;gap junction assembly;embryonic limb morphogenesis;embryonic heart tube development;foramen ovale closure;negative regulation of blood pressure;positive regulation of vasoconstriction;artery morphogenesis;protein complex oligomerization;transmembrane transport;regulation of cardiac muscle contraction;regulation of ventricular cardiac muscle cell membrane repolarization;regulation of atrial cardiac muscle cell membrane depolarization;regulation of ventricular cardiac muscle cell membrane depolarization;ventricular septum morphogenesis;atrial septum morphogenesis;ventricular cardiac muscle cell action potential;SA node cell action potential;SA node cell to atrial cardiac muscle cell communication by electrical coupling;atrial cardiac muscle cell to AV node cell communication by electrical coupling;AV node cell to bundle of His cell communication by electrical coupling;bundle of His cell to Purkinje myocyte communication by electrical coupling;Purkinje myocyte to ventricular cardiac muscle cell communication by electrical coupling;cell communication by electrical coupling involved in cardiac conduction;regulation of heart rate by cardiac conduction;positive regulation of blood vessel diameter;regulation of AV node cell action potential;regulation of bundle of His cell action potential;regulation of Purkinje myocyte action potential;regulation of atrial cardiac muscle cell action potential;regulation of renin secretion into blood stream;regulation of membrane depolarization during cardiac muscle cell action potential;vasomotion
• Cellular component: integral component of plasma membrane;gap junction;connexin complex;intercalated disc;cell projection
• Molecular function: gap junction hemi-channel activity;connexin binding;gap junction channel activity involved in SA node cell-atrial cardiac muscle cell electrical coupling;gap junction channel activity involved in cardiac conduction electrical coupling;gap junction channel activity involved in atrial cardiac muscle cell-AV node cell electrical coupling;gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling;gap junction channel activity involved in bundle of His cell-Purkinje myocyte electrical coupling;gap junction channel activity involved in Purkinje myocyte-ventricular cardiac muscle cell electrical coupling;disordered domain specific binding