Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ8GP5L)

• DOT Name: Mucin-21 (MUC21)
• Synonyms: MUC-21; Epiglycanin
• Gene Name: MUC21
• Related Disease:
  Carcinoma
  Depression
  Lung adenocarcinoma
  Major depressive disorder
  Myasthenia gravis
  Neoplasm
  Schizophrenia
  Squamous cell carcinoma
  Type-1 diabetes
  Epithelioid mesothelioma
  Idiopathic interstitial pneumonia
  Mesothelioma
  Systemic lupus erythematosus
• UniProt ID: MUC21_HUMAN
• Pfam ID: PF14654 ; PF05647
• Sequence:
  MKMQKGNVLLMFGLLLHLEAATNSNETSTSANTGSSVISSGASTATNSGSSVTSSGVSTA
  TISGSSVTSNGVSIVTNSEFHTTSSGISTATNSEFSTVSSGISIATNSESSTTSSGASTA
  TNSESSTPSSGASTATNSDSSTTSSGASTATNSDSSTTSSEASTATNSESSTTSSGASTA
  TNSESSTVSSRASTATNSESSTTSSGASTATNSESRTTSNGAGTATNSESSTTSSGASTA
  TNSESSTPSSGAGTATNSESSTTSSGAGTATNSESSTVSSGISTVTNSESSTPSSGANTA
  TNSESSTTSSGANTATNSDSSTTSSGASTATNSESSTTSSGASTATNSESSTTSSGASTA
  TNSGSSTTSSGTSTATNSESSTVSSGASTATTSESSTTSSGASTATNSESSTVSSGASTA
  TNSESSTTSSGANTATNSGSSVTSAGSGTAALTGMHTTSHSASTAVSEAKPGGSLVPWEI
  FLITLVSVVAAVGLFAGLFFCVRNSLSLRNTFNTAVYHPHGLNHGLGPGPGGNHGAPHRP
  RWSPNWFWRRPVSSIAMEMSGRNSGP
• Tissue Specificity: Expressed in lung, large intestine, thymus, and testis. Expressed in normal and malignant bronchial epithelial cells.
• Reactome Pathway:
  Defective C1GALT1C1 causes TNPS (R-HSA-5083632)
  Defective GALNT12 causes CRCS1 (R-HSA-5083636)
  Dectin-2 family (R-HSA-5621480)
  O-linked glycosylation of mucins (R-HSA-913709)
  Termination of O-glycan biosynthesis (R-HSA-977068)
  Defective GALNT3 causes HFTC (R-HSA-5083625)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Biomarker	[1]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[3]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[2]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[5]
Epithelioid mesothelioma	DIS17SNY	Limited	Altered Expression	[6]
Idiopathic interstitial pneumonia	DISH7LPY	Limited	Biomarker	[7]
Mesothelioma	DISKWK9M	Limited	Biomarker	[6]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mucin-21 (MUC21).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Mucin-21 (MUC21).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mucin-21 (MUC21).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Mucin-21 (MUC21).	[10]

References

• [1] Mucin 21 in esophageal squamous epithelia and carcinomas: analysis with glycoform-specific monoclonal antibodies.Glycobiology. 2012 Sep;22(9):1218-26. doi: 10.1093/glycob/cws082. Epub 2012 May 19.
• [2] Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.Mol Psychiatry. 2020 Jul;25(7):1420-1429. doi: 10.1038/s41380-018-0336-6. Epub 2019 Jan 9.
• [3] Specific expression of MUC21 in micropapillary elements of lung adenocarcinomas - Implications for the progression of EGFR-mutated lung adenocarcinomas.PLoS One. 2019 Apr 11;14(4):e0215237. doi: 10.1371/journal.pone.0215237. eCollection 2019.
• [4] Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
• [5] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [6] Mucin 21 is a novel, negative immunohistochemical marker for epithelioid mesothelioma for its differentiation from lung adenocarcinoma.Histopathology. 2019 Mar;74(4):545-554. doi: 10.1111/his.13775. Epub 2019 Jan 15.
• [7] Unique expression profiles of mucin proteins in interstitial pneumonia-associated lung adenocarcinomas.Histol Histopathol. 2019 Nov;34(11):1243-1254. doi: 10.14670/HH-18-114. Epub 2019 Apr 9.
• [8] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.