Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI09KBW)

• DOT Name: Desmin (DES)
• Gene Name: DES
• Related Disease:
  Congenital myopathy
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1I
  Myofibrillar myopathy 1
  X-linked myotubular myopathy
  Advanced cancer
  Amyotrophic lateral sclerosis
  Atrioventricular block
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiomyopathy
  Cardiomyopathy, familial restrictive, 1
  Centronuclear myopathy
  Colorectal carcinoma
  Desmoplastic small round cell tumor
  Familial dilated cardiomyopathy
  Gastric cancer
  Gastric neoplasm
  Gastrointestinal stromal tumour
  Glioblastoma multiforme
  Glomerulonephritis
  Hereditary diffuse gastric adenocarcinoma
  Hypertrophic cardiomyopathy
  Limb-girdle muscular dystrophy
  Malignant soft tissue neoplasm
  Muscular dystrophy
  Neuroblastoma
  Neuromuscular disease
  Renal cell carcinoma
  Restrictive cardiomyopathy
  Sarcoma
  Skeletal muscle disorder
  Arrhythmogenic right ventricular cardiomyopathy
  Atrial fibrillation
  Familial atrial fibrillation
  Myofibrillar myopathy
  Rhabdomyosarcoma
  Neurogenic scapuloperoneal syndrome, Kaeser type
  Obsolete familial isolated dilated cardiomyopathy
  Wilms tumor
  Alexander disease
  Carcinoma
  Cardiac disease
  Congenital diaphragmatic hernia
  Fetal growth restriction
  Undifferentiated carcinoma
• UniProt ID: DESM_HUMAN
• Pfam ID: PF00038 ; PF04732
• Sequence:
  MSQAYSSSQRVSSYRRTFGGAPGFPLGSPLSSPVFPRAGFGSKGSSSSVTSRVYQVSRTS
  GGAGGLGSLRASRLGTTRTPSSYGAGELLDFSLADAVNQEFLTTRTNEKVELQELNDRFA
  NYIEKVRFLEQQNAALAAEVNRLKGREPTRVAELYEEELRELRRQVEVLTNQRARVDVER
  DNLLDDLQRLKAKLQEEIQLKEEAENNLAAFRADVDAATLARIDLERRIESLNEEIAFLK
  KVHEEEIRELQAQLQEQQVQVEMDMSKPDLTAALRDIRAQYETIAAKNISEAEEWYKSKV
  SDLTQAANKNNDALRQAKQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMRELEDRFASEA
  SGYQDNIARLEEEIRHLKDEMARHLREYQDLLNVKMALDVEIATYRKLLEGEESRINLPI
  QTYSALNFRETSPEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL
• Function: Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity. In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures. May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Required for nuclear membrane integrity, via anchoring at the cell tip and nuclear envelope, resulting in maintenance of microtubule-derived intracellular mechanical forces. Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway: Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myopathy	DISLSK9G	Definitive	Biomarker	[1]
Dilated cardiomyopathy	DISX608J	Definitive	Autosomal dominant	[2]
Dilated cardiomyopathy 1I	DISHPYPE	Definitive	Autosomal dominant	[3]
Myofibrillar myopathy 1	DIS99A51	Definitive	Autosomal dominant	[4]
X-linked myotubular myopathy	DISJ95GS	Definitive	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Altered Expression	[7]
Atrioventricular block	DIS8YLE6	Strong	Autosomal dominant	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[10]
Cardiomyopathy, familial restrictive, 1	DIS4AJ17	Strong	Genetic Variation	[11]
Centronuclear myopathy	DISXBEJO	Strong	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Desmoplastic small round cell tumor	DISLI2ME	Strong	Biomarker	[14]
Familial dilated cardiomyopathy	DISBHDU9	Strong	Biomarker	[15]
Gastric cancer	DISXGOUK	Strong	Biomarker	[16]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[16]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Genetic Variation	[17]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[18]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[19]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[16]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Genetic Variation	[20]
Limb-girdle muscular dystrophy	DISI9Y1Z	Strong	Genetic Variation	[21]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[22]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[23]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[24]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[26]
Restrictive cardiomyopathy	DISFAF31	Strong	Genetic Variation	[27]
Sarcoma	DISZDG3U	Strong	Biomarker	[22]
Skeletal muscle disorder	DISR9DGU	Strong	Genetic Variation	[28]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Moderate	Autosomal dominant	[2]
Atrial fibrillation	DIS15W6U	moderate	Biomarker	[29]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[29]
Myofibrillar myopathy	DISF24LW	moderate	Genetic Variation	[30]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[31]
Neurogenic scapuloperoneal syndrome, Kaeser type	DIS2BTIZ	Supportive	Autosomal dominant	[32]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[33]
Wilms tumor	DISB6T16	Disputed	Altered Expression	[34]
Alexander disease	DISDL1IO	Limited	Genetic Variation	[35]
Carcinoma	DISH9F1N	Limited	Altered Expression	[36]
Cardiac disease	DISVO1I5	Limited	Genetic Variation	[37]
Congenital diaphragmatic hernia	DIS0IPVU	Limited	Biomarker	[38]
Fetal growth restriction	DIS5WEJ5	Limited	Biomarker	[39]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[40]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Zalcitabine	DMH7MUV	Approved	Desmin (DES) increases the Cardiotoxicity ADR of Zalcitabine.	[55]
Sulforaphane	DMQY3L0	Investigative	Desmin (DES) affects the binding of Sulforaphane.	[56]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Desmin (DES).	[41]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Desmin (DES).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Desmin (DES).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Desmin (DES).	[44]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Desmin (DES).	[45]
Selenium	DM25CGV	Approved	Selenium increases the expression of Desmin (DES).	[46]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Desmin (DES).	[47]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Desmin (DES).	[48]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Desmin (DES).	[49]
Artesunate	DMR27C8	Approved	Artesunate decreases the expression of Desmin (DES).	[50]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Desmin (DES).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Desmin (DES).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Desmin (DES).	[52]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the expression of Desmin (DES).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Desmin (DES).	[54]

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