Affected pathways in Duchenne muscular dystrophy (WP5356)

Homo sapiens

Disturbed pathways in DMD


Pauladewenter , Ash Iyer , Egon Willighagen , Alex Pico , Kristina Hanspers , Lars Willighagen , Eric Weitz , and Tooba Abbassi-Daloii


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Homo sapiens


Diseases Rare Diseases


Disease Ontology

muscular disease Duchenne muscular dystrophy

Pathway Ontology

altered calcium/calcium-mediated signaling pathway disease pathway muscular disease pathway


Label Type Compact URI Comment
Lactate Metabolite chebi:24996
[Ca2+]mito Metabolite hmdb:HMDB0000464
Ca2+ Metabolite hmdb:HMDB0000464
Ca2+ Metabolite hmdb:HMDB0000464
ROS Metabolite wikidata:Q424361
ROS Metabolite wikidata:Q424361
Ca2+ Metabolite hmdb:HMDB0000464
ATP Metabolite chebi:30616
Fibronectin Metabolite chebi:5058
Collagen Metabolite chebi:3815
Ang 2 Metabolite pubchem.compound:172198 'angiotensin 2 (Ang 2)' Peptide hormone; 'Asp-Arg-Val-Tyr-Ile-His-Pro-Phe Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE), primarily through ACE within the lung (but also present in endothelial cells, kidney epithelial cells, and the brain). Angiotensin II acts on the central nervous system to increase vasopressin production, and also acts on venous and arterial smooth muscle to cause vasoconstriction. Angiotensin II also increases aldosterone secretion; it therefore acts as an endocrine, autocrine/paracrine, and intracrine hormone.' Source: ''
Ca2+ Metabolite hmdb:HMDB0000464
Platelet-activating factor Metabolite hmdb:HMDB0062195
Ca2+ Metabolite hmdb:HMDB0000464
Ca2+ Metabolite hmdb:HMDB0000464
Ca2+ Metabolite hmdb:HMDB0000464
Na+ Metabolite hmdb:HMDB0000588
Ca2+ Metabolite hmdb:HMDB0000464
Na+ Metabolite hmdb:HMDB0000588
Ca2+ Metabolite hmdb:HMDB0000464
Ca2+ Metabolite hmdb:HMDB0000464
ROS Metabolite wikidata:Q424361
Cl- Metabolite hmdb:HMDB0000492
NO Metabolite hmdb:HMDB0003378
H2O2 Metabolite hmdb:HMDB0003125
HOCl Metabolite hmdb:HMDB0001050 Hypochlorous acid (HOCl) is a type of reactive oxygen species which is produced within neutrophils, and can enter the muscle tissue where it promotes oxidative stress
L-Arginie Metabolite hmdb:HMDB0000517
HOCl Metabolite hmdb:HMDB0001050
RYR1 GeneProduct hgnc.symbol:RYR1
NOX2 GeneProduct uniprot:P04839
SOCE GeneProduct hgnc.symbol:SARAF
Dystrophin deficiency GeneProduct hgnc.symbol:DMD
DMD GeneProduct hgnc.symbol:DMD
DMD(+mutation) GeneProduct hgnc.symbol:DMD
TGF-B1 GeneProduct ensembl:ENSG00000105329
ADT2 GeneProduct hgnc.symbol:SLC25A5
OPN GeneProduct hgnc.symbol:SPP1
TGFBR2 GeneProduct hgnc.symbol:TGFBR2
TGFBR1 GeneProduct hgnc.symbol:TGFBR1
SERPINE1 GeneProduct hgnc.symbol:SERPINE1 Also known as plasminogen activator inhibitor-1 PAI-1
PLAU GeneProduct hgnc.symbol:PLAU Also known as Urokinase-type plasminogen inhibitor (uPA)
IL-6 GeneProduct ensembl:ENSG00000136244 In DMD, IL-6 is upregulated due to recurrent activation of the M1 macrophages by DAMPs. When upregulated for prolonged periods of time, the IL-6 will cause chronic inflammation and also reduce the population of the satellite cells that are needed for muscle regeneration.
IL-1B GeneProduct ensembl:ENSG00000115008
SMAD2 GeneProduct hgnc.symbol:SMAD2
SMAD3 GeneProduct hgnc.symbol:SMAD3
NOX4 GeneProduct hgnc.symbol:NOX4
CTGF GeneProduct hgnc.symbol:CCN2
TNF-a GeneProduct ensembl:ENSG00000232810
AGTR1 GeneProduct hgnc.symbol:AGTR1
Dystrobrevin alpha GeneProduct hgnc.symbol:DTNA
Syntrophin beta-1 GeneProduct hgnc.symbol:SNTB1
alpha sarcoglycan GeneProduct hgnc.symbol:SGCA
Sarcospan GeneProduct hgnc.symbol:SSPN
Dystrophin GeneProduct hgnc.symbol:DMD
Dystroglycan 1 GeneProduct hgnc.symbol:DAG1
STIM1 GeneProduct ensembl:ENSG00000167323
Orai1 GeneProduct ensembl:ENSG00000276045
RYR1 GeneProduct hgnc.symbol:RYR1
CAC1F GeneProduct ensembl:ENSG00000102001 Voltage-dependent L-type calcium channel subunit alpha-1F
CAC1S GeneProduct ensembl:ENSG00000081248 Voltage-dependent L-type calcium channel subunit alpha-1S
CACB2 GeneProduct ensembl:ENSG00000165995 Voltage-dependent L-type calcium channel subunit beta-2
CACB1 GeneProduct ensembl:ENSG00000067191 Voltage-dependent L-type calcium channel subunit beta-1. Only isoform 2 is present in skeletal muscles
CA2D1 GeneProduct ensembl:ENSG00000153956 Voltage-dependent calcium channel subunit alpha-2/delta-1. Only isoform 1 is found in the skeletal muscles
CCG1 GeneProduct ensembl:ENSG00000108878 Voltage-dependent calcium channel subunit gamma-1
DMD (+mutations) GeneProduct ensembl:ENSG00000198947
Calstabin-1 GeneProduct ensembl:ENSG00000088832 Often, there is Ca2+ leakage from the RyRs in the SR, but this process is limited by calstabin-1. Calstabin-1 is a protein which has a high affinity for RyR, stimulated by the dystrophin. However, due to DMD mutations and thus reduction of dystrophin, the Calstabin-1 no longer binds with such a high affinity to the RyR, thus not blocking the calcium leakage
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IL-1α GeneProduct ensembl:ENSG00000115008
IL-6 GeneProduct ensembl:ENSG00000136244 In DMD, IL-6 is upregulated due to recurrent activation of the M1 macrophages by DAMPs. When upregulated for prolonged periods of time, the IL-6 will cause chronic inflammation and also reduce the population of the satellite cells that are needed for muscle regeneration.
IL-10 GeneProduct ensembl:ENSG00000136634
NFkB GeneProduct ensembl:ENSG00000109320
IκBα GeneProduct ensembl:ENSG00000100906
Calpain-3 GeneProduct ensembl:ENSG00000092529
TGF-β GeneProduct ensembl:ENSG00000105329
TNF-α GeneProduct ensembl:ENSG00000232810
Phospholipase A2 GeneProduct ensembl:ENSG00000116711
NFkB GeneProduct ensembl:ENSG00000109320
TRPC3 GeneProduct ensembl:ENSG00000138741 Short transient receptor potential channel 3
TRPC1 GeneProduct ensembl:ENSG00000144935 Short transient receptor potential channel 1
TRPC6 GeneProduct ensembl:ENSG00000137672 Short transient receptor potential channel 6
CASQ 1 GeneProduct hgnc.symbol:CASQ1
Triadin GeneProduct hgnc.symbol:TRDN
AMPK1 GeneProduct ensembl:ENSG00000132356
NE GeneProduct ensembl:ENSG00000197561 Neutrophil elastase (NE) is a type of serine protease which promotes the formation of neutrophil extracellular traps (NETs), which themselves function to trap invading microbes but also cuase tissue damage as collateral. Although possibly playing a role in the pathophysiology of DMD, it is not yet confirmed if NETs contribute to the muscle damage
MPO GeneProduct ensembl:ENSG00000005381 Myeloperoxidase (MPO) is a potent enzyme which catalyses the production of hypochlorous acid (HOCl) when hydrogen peroxide (H2O2) and chloride ions (Cl-) are present within the neutrophil.
FGG GeneProduct hgnc.symbol:FGG
FGB GeneProduct hgnc.symbol:FGB
FGA GeneProduct hgnc.symbol:FGA
Caspase 9 Protein hgnc.symbol:CASP9
VDAC1 Protein hgnc.symbol:VDAC1
CyP-D Protein hgnc.symbol:PPIF
IP3R2 Protein hgnc.symbol:ITPR2
IP3R3 Protein hgnc.symbol:ITPR3
Phospholipase A2 Protein hgnc.symbol:PLA2G2A
MMP2 Protein hgnc.symbol:MMP2
TOM Protein hgnc.symbol:TOMM20
GL1 Protein hgnc.symbol:GLI1
MCU Protein hgnc.symbol:MCU
IP3R1 Protein uniprot:Q14643
Proteoglycans Protein hgnc.symbol:PRG3
SERCA1 Protein hgnc.symbol:ATP2A1
Glycoproteins Protein hgnc.symbol:GP2
VDAC1 Protein hgnc.symbol:VDAC1
Troponin Protein hgnc.symbol:TNNI1
Calpain-3 Protein hgnc.symbol:CAPN3
MCUb Protein hgnc.symbol:MCUB
MMP9 Protein hgnc.symbol:MMP9
Sig-1R Protein hgnc.symbol:SIGMAR1
GRP75 Protein uniprot:P38646
SMAD4 Protein hgnc.symbol:SMAD4
SMAD2 Protein hgnc.symbol:SMAD2
SMAD3 Protein hgnc.symbol:SMAD3
SCX Protein hgnc.symbol:SCX
Sarcolipin Protein ensembl:ENSG00000170290
CaMK2 Protein ensembl:ENSG00000145349
AMPK2 Protein ensembl:ENSG00000162409
iNOS Protein ensembl:ENSG00000007171


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