KEGG   PATHWAY: hsa05412Help
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
BRITE hierarchy
Pathway map
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
hsa05412

All organismsOrtholog table
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 subunit alpha 1 [KO:K06480]
3673  
ITGA2; integrin subunit alpha 2 [KO:K06481]
3674  
ITGA2B; integrin subunit alpha 2b [KO:K06476]
3675  
ITGA3; integrin subunit alpha 3 [KO:K06482]
3676  
ITGA4; integrin subunit alpha 4 [KO:K06483]
3678  
ITGA5; integrin subunit alpha 5 [KO:K06484]
3655  
ITGA6; integrin subunit alpha 6 [KO:K06485]
3679  
ITGA7; integrin subunit alpha 7 [KO:K06583]
8516  
ITGA8; integrin subunit alpha 8 [KO:K06584]
3680  
ITGA9; integrin subunit alpha 9 [KO:K06585]
8515  
ITGA10; integrin subunit alpha 10 [KO:K06586]
22801  
ITGA11; integrin subunit alpha 11 [KO:K06587]
3685  
ITGAV; integrin subunit alpha V [KO:K06487]
3688  
ITGB1; integrin subunit beta 1 [KO:K05719]
3690  
ITGB3; integrin subunit beta 3 [KO:K06493]
3691  
ITGB4; integrin subunit beta 4 [KO:K06525]
3693  
ITGB5; integrin subunit beta 5 [KO:K06588]
3694  
ITGB6; integrin subunit beta 6 [KO:K06589]
3695  
ITGB7; integrin subunit beta 7 [KO:K06590]
3696  
ITGB8; integrin subunit beta 8 [KO:K06591]
6444  
SGCD; sarcoglycan delta [KO:K12563]
6445  
SGCG; sarcoglycan gamma [KO:K12564]
6442  
SGCA; sarcoglycan alpha [KO:K12565]
6443  
SGCB; sarcoglycan beta [KO:K12566]
1605  
DAG1; dystroglycan 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 beta 1 [KO:K02105]
6932  
TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439  
TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  
TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  
LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
775  
CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
776  
CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
778  
CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
779  
CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
782  
CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
783  
CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
784  
CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
785  
CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
781  
CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
9254  
CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
55799  
CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
93589  
CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
786  
CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
10369  
CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
10368  
CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
27092  
CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
27091  
CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
59285  
CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
59284  
CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
59283  
CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873]
6262  
RYR2; ryanodine receptor 2 [KO:K04962]
1000  
CDH2; cadherin 2 [KO:K06736]
3728  
JUP; junction plakoglobin [KO:K10056]
29119  
CTNNA3; catenin alpha 3 [KO:K05691]
1495  
CTNNA1; catenin alpha 1 [KO:K05691]
1496  
CTNNA2; catenin alpha 2 [KO:K05691]
87  
ACTN1; actinin alpha 1 [KO:K05699]
88  
ACTN2; actinin alpha 2 [KO:K05699]
89  
ACTN3; actinin alpha 3 (gene/pseudogene) [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 [KO:K07372]
3908  
LAMA2; laminin subunit alpha 2 [KO:K05637]
488  
ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:3.6.3.8]
6546  
SLC8A1; solute carrier family 8 member A1 [KO:K05849]
Compound
C00076  
Calcium cation
C01330  
Sodium cation
Reference
  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
  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
  Authors
Fatkin D, Graham RM
  Title
Molecular mechanisms of inherited cardiomyopathies.
  Journal
Physiol Rev 82:945-80 (2002)
Reference
  Authors
Franz WM, Muller OJ, Katus HA
  Title
Cardiomyopathies: from genetics to the prospect of treatment.
  Journal
Lancet 358:1627-37 (2001)
Reference
  Authors
MacRae CA, Birchmeier W, Thierfelder L
  Title
Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism.
  Journal
J Clin Invest 116:1825-8 (2006)
Reference
  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
  Authors
Sen-Chowdhry S, Syrris P, McKenna WJ
  Title
Genetics of right ventricular cardiomyopathy.
  Journal
J Cardiovasc Electrophysiol 16:927-35 (2005)
Reference
  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
 

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