GJA5

Gap junction protein, alpha 5, 40kDa

Identifiers

GJA5 ; ATFB11; CX40

External IDs

OMIM: 121013 MGI: 95716 HomoloGene: 3856 IUPHAR: 726 GeneCards: GJA5 Gene

Gene ontology
Molecular function	• gap junction hemi-channel activity • connexin binding • gap junction channel activity involved in cardiac conduction electrical coupling • gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling
Cellular component	• integral component of plasma membrane • gap junction • connexon complex • intercalated disc • cell projection
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 • positive regulation of vasodilation • artery morphogenesis • protein 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 • atrial cardiac muscle cell action potential • SA node cell action potential • AV node cell to bundle of His cell communication by electrical coupling • cell communication by electrical coupling involved in cardiac conduction • bundle of His cell to Purkinje myocyte communication • regulation of heart rate by cardiac conduction • regulation of renin secretion into blood stream • regulation of membrane depolarization during cardiac muscle cell action potential • vasomotion
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
147.23 – 147.25 Mb

Chr 3:
97.03 – 97.05 Mb

PubMed search

Gap junction alpha-5 protein (GJA5), also known as connexin 40 (Cx40) — is a protein that in humans is encoded by the GJA5 gene.

Function

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.^[1]

GJA5 has been identified as the gene that is responsible for the phenotypes observed with congenital heart diseases on the 1q21.1 location. In case of a duplication of GJA5 tetralogy of Fallot is more common. In case of a deletion other congenital heart diseases than tetralogy of Fallot are more common.^[2]

References

↑ "Entrez Gene: GJA5 gap junction protein, alpha 5, 40kDa".
↑ Soemedi, R. et al. (2011). "DPhenotype-Specific Effect of Chromosome 1q21.1 Rearrangements and GJA5 Duplications in 2436 Congenital Heart Disease Patients and 6760 Controls". Hum. Mol. Genet. doi:10.1093/hmg/ddr589.

Andrew L Harris and Darren Locke (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN 978-1-934115-46-6.
Teunissen BE, Bierhuizen MF (2004). "Transcriptional control of myocardial connexins.". Cardiovasc. Res. 62 (2): 246–55. doi:10.1016/j.cardiores.2003.12.011. PMID 15094345.
Kanter HL, Saffitz JE, Beyer EC (1992). "Cardiac myocytes express multiple gap junction proteins.". Circ. Res. 70 (2): 438–44. doi:10.1161/01.res.70.2.438. PMID 1310450.
Willecke K; Jungbluth S; Dahl E et al. (1991). "Six genes of the human connexin gene family coding for gap junctional proteins are assigned to four different human chromosomes". Eur. J. Cell Biol. 53 (2): 275–80. PMID 1964417.
Chen SC; Davis LM; Westphale EM et al. (1995). "Expression of multiple gap junction proteins in human fetal and infant hearts". Pediatr. Res. 36 (5): 561–6. doi:10.1203/00006450-199411000-00002. PMID 7877871.
Kanter HL, Saffitz JE, Beyer EC (1994). "Molecular cloning of two human cardiac gap junction proteins, connexin40 and connexin45". J. Mol. Cell. Cardiol. 26 (7): 861–8. doi:10.1006/jmcc.1994.1103. PMID 7966354.
Mehta PP; Lokeshwar BL; Schiller PC et al. (1996). "Gap-junctional communication in normal and neoplastic prostate epithelial cells and its regulation by cAMP". Mol. Carcinog. 15 (1): 18–32. doi:10.1002/(SICI)1098-2744(199601)15:1<18::AID-MC4>3.0.CO;2-O. PMID 8561862.
Gelb BD; Zhang J; Cotter PD et al. (1997). "Physical mapping of the human connexin 40 (GJA5), flavin-containing monooxygenase 5, and natriuretic peptide receptor a genes on 1q21". Genomics 39 (3): 409–11. doi:10.1006/geno.1996.4516. PMID 9119381.
Kilarski WM; Dupont E; Coppen S et al. (1998). "Identification of two further gap-junctional proteins, connexin40 and connexin45, in human myometrial smooth muscle cells at term". Eur. J. Cell Biol. 75 (1): 1–8. doi:10.1016/S0171-9335(98)80040-X. PMID 9523149.
van Rijen HV, van Kempen MJ, Postma S, Jongsma HJ (1998). "Tumour necrosis factor alpha alters the expression of connexin43, connexin40, and connexin37 in human umbilical vein endothelial cells". Cytokine 10 (4): 258–64. doi:10.1006/cyto.1997.0287. PMID 9617570.
Vozzi C; Dupont E; Coppen SR et al. (1999). "Chamber-related differences in connexin expression in the human heart". J. Mol. Cell. Cardiol. 31 (5): 991–1003. doi:10.1006/jmcc.1999.0937. PMID 10336839.
Haefliger JA, Goy JJ, Waeber G (2000). "Sporadic cases of dilated cardiomyopathies associated with atrioventricular conduction defects are not linked to mutation within the connexins 40 and 43 genes". Eur. Heart J. 20 (24): 1843. doi:10.1053/euhj.1999.1718. PMID 10581143.
van Rijen HV, van Veen TA, Hermans MM, Jongsma HJ (2000). "Human connexin40 gap junction channels are modulated by cAMP". Cardiovasc. Res. 45 (4): 941–51. doi:10.1016/S0008-6363(99)00373-9. PMID 10728420.
Oviedo-Orta E, Hoy T, Evans WH (2000). "Intercellular communication in the immune system: differential expression of connexin40 and 43, and perturbation of gap junction channel functions in peripheral blood and tonsil human lymphocyte subpopulations". Immunology 99 (4): 578–90. doi:10.1046/j.1365-2567.2000.00991.x. PMC 2327182. PMID 10792506.
Vis JC; Nicholson LF; Faull RL et al. (2002). "Connexin expression in Huntington's diseased human brain". Cell Biol. Int. 22 (11–12): 837–47. doi:10.1006/cbir.1998.0388. PMID 10873295.
Valiunas V, Gemel J, Brink PR, Beyer EC (2001). "Gap junction channels formed by coexpressed connexin40 and connexin43". Am. J. Physiol. Heart Circ. Physiol. 281 (4): H1675–89. PMID 11557558.
Kaba RA; Coppen SR; Dupont E et al. (2003). "Comparison of connexin 43, 40 and 45 expression patterns in the developing human and mouse hearts". Cell Commun. Adhes. 8 (4–6): 339–43. doi:10.3109/15419060109080750. PMID 12064615.
Cronier L; Defamie N; Dupays L et al. (2003). "Connexin expression and gap junctional intercellular communication in human first trimester trophoblast". Mol. Hum. Reprod. 8 (11): 1005–13. doi:10.1093/molehr/8.11.1005. PMID 12397213.
Simon AM, McWhorter AR (2002). "Vascular abnormalities in mice lacking the endothelial gap junction proteins connexin37 and connexin40". Dev. Biol. 251 (2): 206–20. doi:10.1006/dbio.2002.0826. PMID 12435353.
Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Dupays L; Mazurais D; Rücker-Martin C et al. (2003). "Genomic organization and alternative transcripts of the human Connexin40 gene". Gene 305 (1): 79–90. doi:10.1016/S0378-1119(02)01229-5. PMID 12594044.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

Index of cells

Description	Structure nucleus chromosome genetics Organelles peroxisome cytoskeleton centrosome epithelia cilia mitochondria Membranes proteins cell adhesions Membrane transport ion channels vesicular transport solute carrier ABC transporters ATPase oxidoreduction-driven

Disease	Structural peroxisome cytoskeleton cilia mitochondria nucleus scleroprotein Membrane channelopathy solute carrier ATPase ABC transporters other extracellular ligands cell surface receptors intracellular signalling Vesicular transport Pore-forming toxins

GJA5

Function

Related gene problems

See also

References

Further reading