Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJPB2TO)

• DOT Name: Desmoglein-2 (DSG2)
• Synonyms: Cadherin family member 5; HDGC
• Gene Name: DSG2
• Related Disease:
  Arrhythmogenic right ventricular cardiomyopathy
  Arrhythmogenic right ventricular dysplasia 10
  B-cell neoplasm
  Inflammatory bowel disease
  Prostate cancer
  Prostate carcinoma
  Alzheimer disease
  Arrhythmia
  Brugada syndrome
  Carcinoma
  Cardiac disease
  Cardiac failure
  Childhood acute lymphoblastic leukemia
  Clear cell renal carcinoma
  Colitis
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Cowden disease
  Crohn disease
  Dilated cardiomyopathy 1A
  Distal myopathy
  Epithelial neoplasm
  Esophageal squamous cell carcinoma
  Familial dilated cardiomyopathy
  Gastric cancer
  Idiopathic cardiomyopathy
  Matthew-Wood syndrome
  Multiple sclerosis
  Neoplasm
  Non-small-cell lung cancer
  Renal cell carcinoma
  Stomach cancer
  Systemic sclerosis
  Ulcerative colitis
  Ventricular tachycardia
  Adenovirus infection
  Advanced cancer
  Basal cell nevus syndrome
  Hereditary diffuse gastric adenocarcinoma
  Pemphigus vulgaris
  Obsolete familial isolated dilated cardiomyopathy
  Cardiomyopathy
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1BB
  Hepatocellular carcinoma
  Hypertrophic cardiomyopathy
  Melanoma
  Squamous cell carcinoma
• UniProt ID: DSG2_HUMAN
• PDB ID: 2YQG; 5ERD; 5J5J; 6QNT; 6QNU; 6SIT; 7A7D; 7AGF; 7AGG; 8QJX; 8QJY; 8QK3
• Pfam ID: PF00028
• Sequence:
  MARSPGRAYALLLLLICFNVGSGLHLQVLSTRNENKLLPKHPHLVRQKRAWITAPVALRE
  GEDLSKKNPIAKIHSDLAEERGLKITYKYTGKGITEPPFGIFVFNKDTGELNVTSILDRE
  ETPFFLLTGYALDARGNNVEKPLELRIKVLDINDNEPVFTQDVFVGSVEELSAAHTLVMK
  INATDADEPNTLNSKISYRIVSLEPAYPPVFYLNKDTGEIYTTSVTLDREEHSSYTLTVE
  ARDGNGEVTDKPVKQAQVQIRILDVNDNIPVVENKVLEGMVEENQVNVEVTRIKVFDADE
  IGSDNWLANFTFASGNEGGYFHIETDAQTNEGIVTLIKEVDYEEMKNLDFSVIVANKAAF
  HKSIRSKYKPTPIPIKVKVKNVKEGIHFKSSVISIYVSESMDRSSKGQIIGNFQAFDEDT
  GLPAHARYVKLEDRDNWISVDSVTSEIKLAKLPDFESRYVQNGTYTVKIVAISEDYPRKT
  ITGTVLINVEDINDNCPTLIEPVQTICHDAEYVNVTAEDLDGHPNSGPFSFSVIDKPPGM
  AEKWKIARQESTSVLLQQSEKKLGRSEIQFLISDNQGFSCPEKQVLTLTVCECLHGSGCR
  EAQHDSYVGLGPAAIALMILAFLLLLLVPLLLLMCHCGKGAKGFTPIPGTIEMLHPWNNE
  GAPPEDKVVPSFLPVDQGGSLVGRNGVGGMAKEATMKGSSSASIVKGQHEMSEMDGRWEE
  HRSLLSGRATQFTGATGAIMTTETTKTARATGASRDMAGAQAAAVALNEEFLRNYFTDKA
  ASYTEEDENHTAKDCLLVYSQEETESLNASIGCCSFIEGELDDRFLDDLGLKFKTLAEVC
  LGQKIDINKEIEQRQKPATETSMNTASHSLCEQTMVNSENTYSSGSSFPVPKSLQEANAE
  KVTQEIVTERSVSSRQAQKVATPLPDPMASRNVIATETSYVTGSTMPPTTVILGPSQPQS
  LIVTERVYAPASTLVDQPYANEGTVVVTERVIQPHGGGSNPLEGTQHLQDVPYVMVRERE
  SFLAPSSGVQPTLAMPNIAVGQNVTVTERVLAPASTLQSSYQIPTENSMTARNTTVSGAG
  VPGPLPDFGLEESGHSNSTITTSSTRVTKHSTVQHSYS
• Function: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
• Tissue Specificity: All of the tissues tested and carcinomas.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
• Reactome Pathway:
  Keratinization (R-HSA-6805567)
  Formation of the cornified envelope (R-HSA-6809371)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOG GTPase cycle (R-HSA-9013408)
  RAC3 GTPase cycle (R-HSA-9013423)
  Apoptotic cleavage of cell adhesion proteins (R-HSA-351906)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Definitive	Autosomal dominant	[1]
Arrhythmogenic right ventricular dysplasia 10	DIS087RB	Definitive	Autosomal dominant	[2]
B-cell neoplasm	DISVY326	Definitive	Biomarker	[3]
Inflammatory bowel disease	DISGN23E	Definitive	Biomarker	[4]
Prostate cancer	DISF190Y	Definitive	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Arrhythmia	DISFF2NI	Strong	Biomarker	[7]
Brugada syndrome	DISSGN0E	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[10]
Cardiac failure	DISDC067	Strong	Genetic Variation	[11]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[12]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[13]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[14]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[14]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[11]
Cowden disease	DISMYKCE	Strong	Biomarker	[15]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[15]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[12]
Distal myopathy	DIS7F5R0	Strong	Genetic Variation	[16]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[17]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[18]
Familial dilated cardiomyopathy	DISBHDU9	Strong	GermlineCausalMutation	[19]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[20]
Idiopathic cardiomyopathy	DISUGBZL	Strong	Altered Expression	[21]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[22]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[23]
Neoplasm	DISZKGEW	Strong	Biomarker	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[13]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[20]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[26]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[27]
Ventricular tachycardia	DISIBXJ3	Strong	Genetic Variation	[28]
Adenovirus infection	DISUYSBZ	moderate	Biomarker	[29]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[30]
Basal cell nevus syndrome	DIST8BC2	moderate	Biomarker	[31]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	moderate	Genetic Variation	[9]
Pemphigus vulgaris	DISENR62	moderate	Biomarker	[32]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[19]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[33]
Dilated cardiomyopathy	DISX608J	Limited	Autosomal dominant	[1]
Dilated cardiomyopathy 1BB	DISO5CEK	Limited	Autosomal recessive	[2]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[34]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Genetic Variation	[35]
Melanoma	DIS1RRCY	Limited	Altered Expression	[36]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[37]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Desmoglein-2 (DSG2) decreases the response to substance of Arsenic trioxide.	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Desmoglein-2 (DSG2).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Desmoglein-2 (DSG2).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Desmoglein-2 (DSG2).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Desmoglein-2 (DSG2).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Desmoglein-2 (DSG2).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Desmoglein-2 (DSG2).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Desmoglein-2 (DSG2).	[44]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Desmoglein-2 (DSG2).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Desmoglein-2 (DSG2).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Desmoglein-2 (DSG2).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Desmoglein-2 (DSG2).	[48]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Desmoglein-2 (DSG2).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Desmoglein-2 (DSG2).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Desmoglein-2 (DSG2).	[51]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Desmoglein-2 (DSG2).	[52]

References

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