Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGAD3I0)

• DOT Name: Mucin-like protein 3 (MUCL3)
• Synonyms: Diffuse panbronchiolitis critical region protein 1
• Gene Name: MUCL3
• Related Disease:
  Attention deficit hyperactivity disorder
  Bipolar disorder
  Lung adenocarcinoma
  Major depressive disorder
  Membranous glomerulonephritis
  Myasthenia gravis
  Rheumatoid arthritis
  Schizophrenia
  Type-1 diabetes
  Vitiligo
  Advanced cancer
  Asthma
  Colorectal adenoma
  Lung cancer
  Matthew-Wood syndrome
  Neoplasm
  Pancreatic ductal carcinoma
  Retinopathy
  Systemic lupus erythematosus
• UniProt ID: MUCL3_HUMAN
• Sequence:
  MAQPVHSLCSAFGLQCCLLFLLASWGAGATTFQEYQKTGELSTSDHIFPLTPGLVYSIPF
  DHIVLHSGQRPPELPKSTEIHEQKRHCNTTRHSKPTDKPTGNSKTIDHKSSTDNHEAPPT
  SEENSSNQGKDPMIRNQRSVDPADSTTTHKESAGKKHITPAPKSKINCRKSTTGKSTVTR
  KSDKTGRPLEKSMSTLDKTSTSSHKTTTSFHNSGNSQTKQKSTSFPEKITAASKTTYKTT
  GTPEESEKTEDSRTTVASDKLLTKTTKNIQETISANELTQSLAEPTEHGGRTANENNTPS
  PAEPTENRERTANENKKTICTKGKNTPVPEKPTENLGNTTLTTETIKAPVKSTENPEKTA
  AVTKTIKPSVKVTGDKSLTTTSSHLNKTEVTHQVPTGSFTLITSRTKLSSITSEATGNES
  HPYLNKDGSQKGIHAGQMGENDSFPAWAIVIVVLVAVILLLVFLGLIFLVSYMMRTRRTL
  TQNTQYNDAEDEGGPNSYPVYLMEQQNLGMGQIPSPR
• Function: May modulate NF-kappaB signaling and play a role in cell growth.
• Tissue Specificity: Detected in lung, esophagus, stomach, rectum, skin, cervix, testis, kidney, uterus and small intestine . Expressed in pancreas (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[1]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[2]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Membranous glomerulonephritis	DISFSUKQ	Strong	Genetic Variation	[3]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[6]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[7]
Vitiligo	DISR05SL	Strong	Genetic Variation	[8]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[9]
Asthma	DISW9QNS	Limited	Genetic Variation	[10]
Colorectal adenoma	DISTSVHM	Limited	Altered Expression	[11]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[12]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[9]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[9]
Retinopathy	DISB4B0F	Limited	Biomarker	[13]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mucin-like protein 3 (MUCL3).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Mucin-like protein 3 (MUCL3).	[17]
Fenfluramine	DM0762O	Phase 3	Fenfluramine increases the expression of Mucin-like protein 3 (MUCL3).	[18]

2 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-like protein 3 (MUCL3).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mucin-like protein 3 (MUCL3).	[19]

References

• [1] Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.Lancet. 2013 Apr 20;381(9875):1371-1379. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28.
• [2] A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.Am J Hum Genet. 2009 Nov;85(5):679-91. doi: 10.1016/j.ajhg.2009.09.012. Epub 2009 Oct 15.
• [3] Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.N Engl J Med. 2011 Feb 17;364(7):616-26. doi: 10.1056/NEJMoa1009742.
• [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] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [6] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [7] 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.
• [8] Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.Nat Genet. 2010 Jul;42(7):614-8. doi: 10.1038/ng.603. Epub 2010 Jun 6.
• [9] High expression of diffuse panbronchiolitis critical region 1 gene promotes cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma.Biochem Biophys Res Commun. 2018 Jan 8;495(2):1908-1914. doi: 10.1016/j.bbrc.2017.12.031. Epub 2017 Dec 11.
• [10] Effect of diffuse panbronchiolitis critical region 1 polymorphisms on the risk of aspirin-exacerbated respiratory disease in Korean asthmatics.Respir Care. 2012 May;57(5):758-63. doi: 10.4187/respcare.01480. Epub 2011 Dec 6.
• [11] Identification of a novel VNTR polymorphism in C6orf37 and its association with colorectal cancer risk in Chinese population.Clin Chim Acta. 2006 Jun;368(1-2):155-9. doi: 10.1016/j.cca.2005.12.043. Epub 2006 Mar 20.
• [12] Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
• [13] Identification and characterization of C6orf37, a novel candidate human retinal disease gene on chromosome 6q14.Biochem Biophys Res Commun. 2002 Apr 26;293(1):356-65. doi: 10.1016/S0006-291X(02)00228-0.
• [14] 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.
• [15] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [16] 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.
• [17] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [18] Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
• [19] 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.