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FLASH GENE

Symbol

GJA5

contributors: mct - updated : 03-07-2015

HGNC name	gap junction protein, alpha 5, 40kDa
HGNC id	4279

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ATFB11 atrial fibrillation, familial, 11
Location	1q21.2      Physical location : 147.228.331 - 147.245.484
Synonym name	connexin 40
	gap junction protein, alpha 5, 40kDa (connexin 40)
Synonym symbol(s)	CX40, MGC11185, ATFB1A, ATFB11

DNA

TYPE	functioning gene
STRUCTURE	17.15 kb     2 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	exon 1A (100 bp), exon 1B (132 bp) and coding exon 2, with the exons 1A and 1B at 14 and 1.3 kb of the exon 2, respectively
	regulated by the interaction of ubiquitous and tissue-specific factors such as Sp1 and GATA4

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D1S514 - D1S442 - FMO5 - D1S2018E - GJA5- D1S2552 - D1S2612 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005266 2 - 3177 NP_005257 - 358 endothelial cells 2007 17189315 NM_181703 2 - 3156 NP_859054 - 358 placental cytoytophoblast 2007 17189315

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart atrium     highly Homo sapiens   vessel         Homo sapiens Urinary kidney juxtaglomerulus apparatus       Homo sapiens   kidney nephron renal capsule Bowman s capsule   Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth vessel     Muscular striatum cardiac   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte Homo sapiens

cell lineage
cell lines	mesenchymal stem cells
fluid/secretion

at STAGE

physiological period

pregnancy

Text	placental cytotrophoblast (variant B)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four putative membrane spanning alpha helices, separating the N terminal intracellular domain
	two extracellular loops
	a C terminal intracellular domain, interacting with C-terminus of GJA1 (interaction important for the regulation of heteromeric channels)

HOMOLOGY

Homologene

FAMILY	connexin family
	alpha-type (group II) subfamily

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	oligomerize to form intercellular channels, called gap junctions, through which ions and small molecules move between adjacent cells
	through both fast and slow gating mechanisms, exhibit a negative gating polarity
	plays a predominant role in the formation of gap junctions in the vasculature, participates in the autoregulation of renal blood flow (RBF)
	major gap-junction protein in the atrial myocardium
	its expression plays a functional role in flow-driven arteriogenesis
	central role potentially for the development and function of renin-producing cells and for tubuloglomerular signal transmission
	plays an important role in signal propagation along blood vessel walls, modulating vessel diameter and thereby blood flow

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

monomer constituent of the connexon (six subunits), docking with its counterpart in the neighboring cell to form the gap junction channel

INTERACTION

DNA

RNA

small molecule

protein	GJA4, GJA5, contribute to the propagation and amplification of the Ca(2+) signaling triggered by Acetylcholine (ACh) in endothelial cells expressing CHRM3
	intermittent hypoxia causes reductions and remodeling of atrial GJA5, GJA1, generated in response to reactive oxygen species by CYBB, and likely contributing to the substrate for atrial fibrillation that develops in response to obstructive sleep apnea

cell & other

REGULATION

inhibited by

by inhibiting PI3K or AKT1, with PI3K activity being required for basal GJA5 expression and AKT1 activity taking part in its shear stress-dependent induction

Other

regulated by IRX3, that likely regulates GJA5 indirectly, activating GJA5 expression by suppressing the transcription of a GJA5 repressor

ASSOCIATED DISORDERS

corresponding disease(s)

ATFB11

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in ischemic cardiomyopathy constitutional   deletion     1q21.1 contiguous gene deletion (with ACP6 and GJA8)associated with a range of cardiac defects, with particularly anomalies of the aortic arch constitutional somatic mutation       in idiopathic atrial fibrillation by impairing gap-junction assembly or electrical coupling constitutional   amplification     recurring copy-number variants in congenital heart disease

Susceptibility

to atrial cardiomyopathy with heart block (see ATFB1A) to essential hypertension in men to Tetralogy of Fallot

Variant & Polymorphism other	somatic mutations in atrial cardiomyopathy with heart block
	polymorphisms increasing the risk of essential hypertension in men
	A96S mutation, the aberrant extravascular localization of renin-secreting cells in the kidney likely impairs the pressure-mediated inhibition of renin secretion, and is associated to essential hypertension

Candidate gene	for the CHD phenotypes observed with dup 1q21
Marker
Therapy target

ANIMAL & CELL MODELS

	deletion of the gap-junction-forming protein GJA5 leads to renin-dependent hypertension in mice
	sinus node impulse initiation was found to be ectopic in Cx40(-/-) mice at 15.5 days postcoitus