KEGG PATHWAY: hsa05412

PATHWAY: hsa05412

Entry

hsa05412 Pathway

Name

Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)

Description

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVC. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.

Class

Human Diseases; Cardiovascular diseases

Pathway map

hsa05412

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

Disease

H00293	Arrhythmogenic right ventricular cardiomyopathy (ARVC)
H00669	Naxos disease and Carvajal syndrome
H00728	Brugada syndrome (BRS)

Organism

Homo sapiens (human) [GN:hsa]

Gene

3672	ITGA1; integrin, alpha 1 [KO:K06480]
3673	ITGA2; integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) [KO:K06481]
3674	ITGA2B; integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41) [KO:K06476]
3675	ITGA3; integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor) [KO:K06482]
3676	ITGA4; integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) [KO:K06483]
3678	ITGA5; integrin, alpha 5 (fibronectin receptor, alpha polypeptide) [KO:K06484]
3655	ITGA6; integrin, alpha 6 [KO:K06485]
3679	ITGA7; integrin, alpha 7 [KO:K06583]
8516	ITGA8; integrin, alpha 8 [KO:K06584]
3680	ITGA9; integrin, alpha 9 [KO:K06585]
8515	ITGA10; integrin, alpha 10 [KO:K06586]
101060422	integrin alpha-10-like; K06586 integrin alpha 10 [KO:K06586]
22801	ITGA11; integrin, alpha 11 [KO:K06587]
3685	ITGAV; integrin, alpha V [KO:K06487]
3688	ITGB1; integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) [KO:K05719]
3690	ITGB3; integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) [KO:K06493]
3691	ITGB4; integrin, beta 4 [KO:K06525]
3693	ITGB5; integrin, beta 5 [KO:K06588]
3694	ITGB6; integrin, beta 6 [KO:K06589]
3695	ITGB7; integrin, beta 7 [KO:K06590]
3696	ITGB8; integrin, beta 8 [KO:K06591]
6444	SGCD; sarcoglycan, delta (35kDa dystrophin-associated glycoprotein) [KO:K12563]
6445	SGCG; sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) [KO:K12564]
6442	SGCA; sarcoglycan, alpha (50kDa dystrophin-associated glycoprotein) [KO:K12565]
6443	SGCB; sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) [KO:K12566]
1605	DAG1; dystroglycan 1 (dystrophin-associated glycoprotein 1) [KO:K06265]
1756	DMD; dystrophin [KO:K10366]
1674	DES; desmin [KO:K07610]
60	ACTB; actin, beta [KO:K05692]
71	ACTG1; actin, gamma 1 [KO:K05692]
2010	EMD; emerin [KO:K12569]
4000	LMNA; lamin A/C [KO:K12641]
1499	CTNNB1; catenin (cadherin-associated protein), beta 1, 88kDa [KO:K02105]
6932	TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439	TCF7L1; transcription factor 7-like 1 (T-cell specific, HMG-box) [KO:K04490]
6934	TCF7L2; transcription factor 7-like 2 (T-cell specific, HMG-box) [KO:K04491]
51176	LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
775	CACNA1C; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
776	CACNA1D; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
778	CACNA1F; calcium channel, voltage-dependent, L type, alpha 1F subunit [KO:K04853]
779	CACNA1S; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
782	CACNB1; calcium channel, voltage-dependent, beta 1 subunit [KO:K04862]
783	CACNB2; calcium channel, voltage-dependent, beta 2 subunit [KO:K04863]
784	CACNB3; calcium channel, voltage-dependent, beta 3 subunit [KO:K04864]
785	CACNB4; calcium channel, voltage-dependent, beta 4 subunit [KO:K04865]
781	CACNA2D1; calcium channel, voltage-dependent, alpha 2/delta subunit 1 [KO:K04858]
9254	CACNA2D2; calcium channel, voltage-dependent, alpha 2/delta subunit 2 [KO:K04859]
55799	CACNA2D3; calcium channel, voltage-dependent, alpha 2/delta subunit 3 [KO:K04860]
93589	CACNA2D4; calcium channel, voltage-dependent, alpha 2/delta subunit 4 [KO:K04861]
786	CACNG1; calcium channel, voltage-dependent, gamma subunit 1 [KO:K04866]
10369	CACNG2; calcium channel, voltage-dependent, gamma subunit 2 [KO:K04867]
10368	CACNG3; calcium channel, voltage-dependent, gamma subunit 3 [KO:K04868]
27092	CACNG4; calcium channel, voltage-dependent, gamma subunit 4 [KO:K04869]
27091	CACNG5; calcium channel, voltage-dependent, gamma subunit 5 [KO:K04870]
59285	CACNG6; calcium channel, voltage-dependent, gamma subunit 6 [KO:K04871]
59284	CACNG7; calcium channel, voltage-dependent, gamma subunit 7 [KO:K04872]
59283	CACNG8; calcium channel, voltage-dependent, gamma subunit 8 [KO:K04873]
6262	RYR2; ryanodine receptor 2 (cardiac) [KO:K04962]
1000	CDH2; cadherin 2, type 1, N-cadherin (neuronal) [KO:K06736]
3728	JUP; junction plakoglobin [KO:K10056]
29119	CTNNA3; catenin (cadherin-associated protein), alpha 3 [KO:K05691]
1495	CTNNA1; catenin (cadherin-associated protein), alpha 1, 102kDa [KO:K05691]
1496	CTNNA2; catenin (cadherin-associated protein), alpha 2 [KO:K05691]
87	ACTN1; actinin, alpha 1 [KO:K05699]
88	ACTN2; actinin, alpha 2 [KO:K05699]
89	ACTN3; actinin, alpha 3 [KO:K05699]
81	ACTN4; actinin, alpha 4 [KO:K05699]
1824	DSC2; desmocollin 2 [KO:K07601]
5318	PKP2; plakophilin 2 [KO:K12642]
1832	DSP; desmoplakin [KO:K10381]
1829	DSG2; desmoglein 2 [KO:K07597]
2697	GJA1; gap junction protein, alpha 1, 43kDa [KO:K07372]
3908	LAMA2; laminin, alpha 2 [KO:K05637]
488	ATP2A2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853] [EC:3.6.3.8]
6546	SLC8A1; solute carrier family 8 (sodium/calcium exchanger), member 1 [KO:K05849]

Compound

C00076	Calcium cation
C01330	Sodium cation

Reference

PMID:19205777

Authors

Herren T, Gerber PA, Duru F

Title

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare "disease of the desmosome" with multiple clinical presentations.

Journal

Clin Res Cardiol 98:141-58 (2009)

Reference

PMID:17413274

Authors

van Tintelen JP, Hofstra RM, Wiesfeld AC, van den Berg MP, Hauer RN, Jongbloed JD

Title

Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon?

Journal

Curr Opin Cardiol 22:185-92 (2007)

Reference

PMID:12270949

Authors

Fatkin D, Graham RM

Title

Molecular mechanisms of inherited cardiomyopathies.

Journal

Physiol Rev 82:945-80 (2002)

Reference

PMID:11716909

Authors

Franz WM, Muller OJ, Katus HA

Title

Cardiomyopathies: from genetics to the prospect of treatment.

Journal

Lancet 358:1627-37 (2001)

Reference

PMID:16823481

Authors

MacRae CA, Birchmeier W, Thierfelder L

Title

Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism.

Journal

J Clin Invest 116:1825-8 (2006)

Reference

PMID:18382419

Authors

Awad MM, Calkins H, Judge DP

Title

Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Journal

Nat Clin Pract Cardiovasc Med 5:258-67 (2008)

Reference

PMID:16101641

Authors

Sen-Chowdhry S, Syrris P, McKenna WJ

Title

Genetics of right ventricular cardiomyopathy.

Journal

J Cardiovasc Electrophysiol 16:927-35 (2005)

Reference

PMID:16124859

Authors

Ahmad F, Seidman JG, Seidman CE

Title

The genetic basis for cardiac remodeling.

Journal

Annu Rev Genomics Hum Genet 6:185-216 (2005)

KO pathway

ko05412

All links

Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
   BioSystems (1)   
Disease (3)   
   KEGG DISEASE (3)   
Genome (1)   
   KEGG GENOME (1)   
Gene (75)   
   KEGG GENES (75)   
All databases (83)   

Download RDF

DBGET integrated database retrieval system