KEGG   PATHWAY: hsa05410Help
Entry
hsa05410                    Pathway                                

Name
Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
Description
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myfibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in the genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myfilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction.
Class
Human Diseases; Cardiovascular diseases
BRITE hierarchy
Pathway map
Hypertrophic cardiomyopathy (HCM)
hsa05410

All organismsOrtholog table
Disease
H00292  
Hypertrophic cardiomyopathy (HCM)
H00728  
Brugada syndrome (BRS)
H01154  
Wolff-Parkinson-White (WPW) syndrome
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]
1674  
DES; desmin [KO:K07610]
1756  
DMD; dystrophin [KO:K10366]
60  
ACTB; actin, beta [KO:K05692]
71  
ACTG1; actin gamma 1 [KO:K05692]
7273  
TTN; titin [KO:K12567] [EC:2.7.11.1]
7139  
TNNT2; troponin T2, cardiac type [KO:K12045]
7134  
TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
7137  
TNNI3; troponin I3, cardiac type [KO:K12044]
70  
ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
7168  
TPM1; tropomyosin 1 (alpha) [KO:K10373]
7169  
TPM2; tropomyosin 2 (beta) [KO:K10374]
7170  
TPM3; tropomyosin 3 [KO:K09290]
7171  
TPM4; tropomyosin 4 [KO:K10375]
4607  
MYBPC3; myosin binding protein C, cardiac [KO:K12568]
4634  
MYL3; myosin light chain 3 [KO:K12749]
4633  
MYL2; myosin light chain 2 [KO:K10351]
2010  
EMD; emerin [KO:K12569]
4000  
LMNA; lamin A/C [KO:K12641]
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]
5562  
PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.11]
5563  
PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.11]
5564  
PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
5565  
PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
5571  
PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
53632  
PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
51422  
PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
1636  
ACE; angiotensin I converting enzyme [KO:K01283] [EC:3.4.15.1]
3479  
IGF1; insulin like growth factor 1 [KO:K05459]
7040  
TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  
TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  
TGFB3; transforming growth factor beta 3 [KO:K13377]
7124  
TNF; tumor necrosis factor [KO:K03156]
3569  
IL6; interleukin 6 [KO:K05405]
3908  
LAMA2; laminin subunit alpha 2 [KO:K05637]
4624  
MYH6; myosin, heavy chain 6, cardiac muscle, alpha [KO:K17751]
4625  
MYH7; myosin, heavy chain 7, cardiac muscle, beta [KO:K17751]
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
C00002  
ATP
C00076  
Calcium cation
C01330  
Sodium cation
C02135  
Angiotensin II
C16010  
Endothelin-1
Reference
  Authors
Fatkin D, Graham RM
  Title
Molecular mechanisms of inherited cardiomyopathies.
  Journal
Physiol Rev 82:945-80 (2002)
Reference
  Authors
Moolman-Smook JC, Mayosi BM, Brink PA, Corfield VA
  Title
Molecular genetics of cardiomyopathy: changing times, shifting paradigms.
  Journal
Cardiovasc J S Afr 14:145-55 (2003)
Reference
  Authors
Taylor MR, Carniel E, Mestroni L
  Title
Familial hypertrophic cardiomyopathy: clinical features, molecular genetics and molecular genetic testing.
  Journal
Expert Rev Mol Diagn 4:99-113 (2004)
Reference
  Authors
Tei C (ed).
  Title
[Up to date of basic and clinical aspects of cardiomyopathies] (In Japanese)
  Journal
Ishiyakushupan (2009)
Reference
  Authors
Marian AJ
  Title
Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy.
  Journal
Lancet 355:58-60 (2000)
Reference
  Authors
Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H
  Title
Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis.
  Journal
Hum Mol Genet 10:1215-20 (2001)
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
Morimoto S
  Title
Sarcomeric proteins and inherited cardiomyopathies.
  Journal
Cardiovasc Res 77:659-66 (2008)
Reference
  Authors
Cambronero F, Marin F, Roldan V, Hernandez-Romero D, Valdes M, Lip GY
  Title
Biomarkers of pathophysiology in hypertrophic cardiomyopathy: implications for clinical management and prognosis.
  Journal
Eur Heart J 30:139-51 (2009)
Reference
  Authors
Towbin JA, Bowles NE
  Title
The failing heart.
  Journal
Nature 415:227-33 (2002)
Reference
  Authors
Sorajja P, Elliott PM, McKenna WJ
  Title
The molecular genetics of hypertrophic cardiomyopathy: prognostic implications.
  Journal
Europace 2:4-14 (2000)
Reference
  Authors
Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, Ommen SR, Potter JD, Ackerman MJ
  Title
Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C.
  Journal
J Mol Cell Cardiol 45:281-8 (2008)
KO pathway
 

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