Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI4XUDY)

• DOT Name: Mucin-3A (MUC3A)
• Synonyms: MUC-3A; Intestinal mucin-3A
• Gene Name: MUC3A
• Related Disease:
  Advanced cancer
  Colon carcinoma
  Adenocarcinoma
  Adenoma
  Barrett esophagus
  Breast cancer
  Breast carcinoma
  Carcinoma
  Clear cell adenocarcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Crohn disease
  Ductal carcinoma
  Gastric adenocarcinoma
  Inflammatory bowel disease
  Laryngitis
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Mucinous adenocarcinoma
  Ovarian cancer
  Pancreatic adenocarcinoma
  Pancreatic ductal carcinoma
  Renal cell carcinoma
  Signet ring cell carcinoma
  Ulcerative colitis
  Colon cancer
  Ductal breast carcinoma in situ
  Gastric cancer
  Stomach cancer
  Arthritis
  Minimally invasive lung adenocarcinoma
  Rheumatoid arthritis
• UniProt ID: MUC3A_HUMAN
• Sequence:
  MQLLGLLGLLWMLKASPWATGTLSTATSISQVPFPRAEAASAVLSNSPHSRDLAGWPLGV
  PQLASPAPGHRENAPMTLTTSPHDTLISETLLNSPVSSNTSTTPTSKFAFKVETTPPTVL
  VYSATTECVYPTSFIITISHPTSICVTTTQVAFTSSYTSTPVTQKPVTTVTSTYSMTTTE
  KGTSAMTSSPSTTTARETPIVTVTPSSVSATDTTFHTTISSTTRTTERTPLPTGSIHTTT
  SPTPVFTTLKTAVTSTSPITSSITSTNTVTSMTTTASQPTATNTLSSPTRTILSSTPVLS
  TETITSGITNTTPLSTLVTTLPTTISRSTPTSETTYTTSPTSTVTDSTTKIAYSTSMTGT
  LSTETSLPPTSSSLPTTETATTPMTNLVTTTTEISSHSTPSFSSSTIYSTVSTSTTAISS
  LPPTSGTMVTSTTMTPSSLSTDIPFTTPTTITHHSVGSTGFLTTATDLTSTFTVSSSSAM
  STSVIPSSPSIQNTETSSLVSMTSATTPNVRPTFVSTLSTPTSSLLTTFPATYSFSSSMS
  ASSAGTTHTESISSPPASTSTLHTTAESTLAPTTTTSFTTSTTMEPPSTTAATTGTGQTT
  FTSSTATFPETTTPTPTTDMSTESLTTAMTSPPITSSVTSTNTVTSMTTTTSPPTTTNSF
  TSLTSMPLSSTPVPSTEVVTSGTINTIPPSILVTTLPTPNASSMTTSETTYPNSPTGPGT
  NSTTEITYPTTMTETSSTATSLPPTSPLVSTAKTAKTPTTNLVTTTTKTTSHSTTSFTSS
  TVYSTASTYTTAITSVPTTLGTMVTSTSMISSTVSTGIPTSQPTTITPSSVGISGSLPMM
  TDLTSVYTVSNMSARPTTVIPSSPTVQNTEISISVSMTSATTPSGGPTFTSTENTPTRSL
  LTSFPMTHSFSSSMSESSAGTTHTESISSPRGTTSTLHTTVESTPSPTTTTSFTTSTMME
  PPSSTVSTTGRGQTTFPSSTATFPETTTLTPTTDISTVSLTTAMTSPPPVSSSITPTNTM
  TSMRTTTYWPTATNTLSPLTSSILSSTPVPSTEMITSHTTNTTPLSTLVTTLLTTITRST
  PTSETTYPTSPTSIVSDSTTEITYSTSITGTLSTATTLPPTSSSLPTTETATMTPTTTLI
  TTTPNTTSLSTPSFTSSTIYSTVSTSTTAISSASPTSGTMVTSTTMTPSSLSTDTPSTTP
  TTITYPSVGSTGFLTTATDLTSTFTVSSSSAMSTSVIPSSPSIQNTETSSLVSMTSATTP
  SLRPTITSTDSTLTSSLLTTFPSTYSFSSSMSASSAGTTHTETISSLPASTNTIHTTAES
  ALAPTTTTSFTTSPTMEPPSTTVATTGTGQTTFPSSTATFLETTTLTPTTDFSTESLTTA
  MTSTPPITSSITPTDTMTSMRTTTSWPTATNTLSPLTSSILSSTPVPSTEVTTSHTTNTN
  PVSTLVTTLPITITRSTLTSETAYPSSPTSTVTESTTEITYPTTMTETSSTATSLPPTSS
  LVSTAETAKTPTTNLVTTTTKTTSHSTTSFTSSTIYSTASTPTTAITSVPTTLGTMVTST
  SMIPSTVSTGIPTSQPTTITPSSVGISGSLPMMTDLTSVYTVSSMSARPTSVIPSSPTVQ
  NTETSIFVSMMSATTPSGGPTFTSTENTPTRSLLTSFPVTHSFSSSMSASSVGTTHTQSI
  SSPPAITSTLHTTAESTPSPTTTMSFTTFTKMETPSSTVATTGTGQTTFTSSTATSPKTT
  TLTPTSDISTGSFKTAVSSTPPITSSITSTYTVTSMTTTTPLGPTATNTLPSFTSSVSSS
  TPVPSTEAITSGTTNTTPLSTLVTTFSNSDTSSTPTSETTYPTSLTSALTDSTTRTTYST
  NMTGTLSTVTSLRPTSSSLLTTVTATVPTTNLVTTTTKITSHSTPSFTSSIATTETPSHS
  TPRFTSSITTTETPSHSTPRFTSSITNTKTTSHSSPSFTSSITTTETTSHNTPSLTSSIT
  TTKTTSHSTPSYTSLITTTTTTSHSTPSFTSSITTTETTSHNTPSLTSSITTTETTSHST
  PSFTSSITTETTSHSTPSFTSLITITEITSHSTLSYTTSITTTETPSHSTLSFTSSITTT
  ETTSHSTPSFTSSITTSEMPSHSTPSFTSSITTTENATHSTPNFTSSITTTETTSHSTPS
  FTSLITTTETTSHRWGTTETTSYSTPSFTSSNTITETTSHSTPSYITSITTTETPSSSTP
  SFSSSITTTETTSHSTPGFTSSITTTETTSHSTPSFTSSITTTETTSHDTPSFTSSITTS
  ETPSHSTPSSTSLITTTKTTSHSTPSFTSSITTTETTSHSAHSFTSSITTTETTSHNTRS
  FTSSITTTETNSHSTTSFTSSITTTETTSHSTPSFSSSITTTETPLHSTPGLTSWVTTTK
  TTSHITPGLTSSITTTETTSHSTPGFTSSITTTETTSESTPSLSSSTIYSTVSTSTTAIT
  SHFTTSETAVTPTPVTPSSLSTDIPTTSLRTLTPSSVGTSTSLTTTTDFPSIPTDISTLP
  TRTHIISSSPSIQSTETSSLVGTTSPTMSTVRMTLRITENTPISSFSTSIVVIPETPTQT
  PPVLTSATGTQTSPAPTTVTFGSTDSSTSTLHTLTPSTALSTIVSTSQVPIPSTHSSTLQ
  TTPSTPSLQTSLTSTSEFTTESFTRGSTSTNAILTSFSTIIWSSTPTIIMSSSPSSASIT
  PVFSTTIHSVPSSPYIFSTENVGSASITGFPSLSSSATTSTSSTSSSLTTALTEITPFSY
  ISLPSTTPCPGTITITIVPASPTDPCVEMDPSTEATSPPTTPLTVFPFTTEMVTCPTSIS
  IQTTLTTYMDTSSMMPESESSISPNASSSTGTGTVPTNTVFTSTRLPTSETWLSNSSVIP
  LPLPGVSTIPLTMKPSSSLPTILRTSSKSTHPSPPTTRTSETPVATTQTPTTLTSRRTTR
  ITSQMTTQSTLTTTAGTCDNGGTWEQGQCACLPGFSGDRCQLQTRCQNGGQWDGLKCQCP
  STFYGSSCEFAVEQVDLDVVETEVGMEVSVDQQFSPDLNDNTSQAYRDFNKTFWNQMQKI
  FADMQGFTFKGVEILSLRNGSIVVDYLVLLEMPFSPQLESEYEQVKTTLKEGLQNASQDV
  NSCQDSQTLCFKPDSIKVNNNSKTELTPAAICRRAAPTGYEEFYFPLVEATRLRCVTKCT
  SGVDNAIDCHQGQCVLETSGPTCRCYSTDTHWFSGPRCEVAVHWRALVGGLTAGAALLVL
  LLLALGVRAVRSGWWGGQRRGRSWDQDRKWFETWDEEVVGTFSNWGFEDDGTDKDTNFYV
  ALENVDTTMKVHIKRPEMTSSSV
• Function: Major glycoprotein component of a variety of mucus gels. Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. May be involved in ligand binding and intracellular signaling.
• Tissue Specificity: Broad specificity; small intestine, colon, colonic tumors, heart, liver, thymus, prostate, pancreas and gall bladder.
• 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

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Posttranslational Modification	[1]
Colon carcinoma	DISJYKUO	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Clear cell adenocarcinoma	DISYUGHZ	Strong	Altered Expression	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[9]
Ductal carcinoma	DIS15EA5	Strong	Altered Expression	[10]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[11]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[12]
Laryngitis	DISX7UUD	Strong	Altered Expression	[13]
Lung cancer	DISCM4YA	Strong	Altered Expression	[14]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[14]
Lung neoplasm	DISVARNB	Strong	Biomarker	[14]
Mucinous adenocarcinoma	DISKNFE8	Strong	Genetic Variation	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[16]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Altered Expression	[10]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Biomarker	[10]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[6]
Signet ring cell carcinoma	DISVCUCR	Strong	Genetic Variation	[17]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[18]
Colon cancer	DISVC52G	moderate	Altered Expression	[1]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Biomarker	[19]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[20]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[20]
Arthritis	DIST1YEL	Limited	Altered Expression	[21]
Minimally invasive lung adenocarcinoma	DIS4W83X	Limited	Altered Expression	[22]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Mucin-3A (MUC3A) decreases the response to substance of Arsenic trioxide.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Mucin-3A (MUC3A).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Mucin-3A (MUC3A).	[24]

References

• [1] Promoter hypomethylation contributes to the expression of MUC3A in cancer cells.Biochem Biophys Res Commun. 2010 Jun 25;397(2):333-9. doi: 10.1016/j.bbrc.2010.05.124. Epub 2010 May 27.
• [2] Dynamics of SOX2 and CDX2 Expression in Barrett's Mucosa.Dis Markers. 2016;2016:1532791. doi: 10.1155/2016/1532791. Epub 2016 Sep 27.
• [3] Mucin gene transcripts in benign and borderline mucinous tumours of the ovary: an in situ hybridization study.J Pathol. 2001 Mar;193(3):339-44. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH798>3.0.CO;2-9.
• [4] Math1/Atoh1 contributes to intestinalization of esophageal keratinocytes by inducing the expression of Muc2 and Keratin-20.Dig Dis Sci. 2012 Apr;57(4):845-57. doi: 10.1007/s10620-011-1998-y. Epub 2011 Dec 7.
• [5] Mucin synthesis and secretion in various human epithelial cancer cell lines that express the MUC-1 mucin gene.Cancer Res. 1993 Mar 15;53(6):1437-43.
• [6] Expression of human mucin genes in normal kidney and renal cell carcinoma.Histopathology. 2002 May;40(5):450-7. doi: 10.1046/j.1365-2559.2002.01408.x.
• [7] Quantitative RT-PCR assay for MUC3 and VEGF mRNA in renal clear cell carcinoma: relationship with nuclear grade and prognosis.Urology. 2003 Oct;62(4):771-5. doi: 10.1016/s0090-4295(03)00560-0.
• [8] The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer.World J Surg Oncol. 2007 Mar 9;5:31. doi: 10.1186/1477-7819-5-31.
• [9] Mucin gene expression in intestinal epithelial cells in Crohn's disease.Gut. 2001 Oct;49(4):544-51. doi: 10.1136/gut.49.4.544.
• [10] Aberrant expression of MUC3 and MUC4 membrane-associated mucins and sialyl Le(x) antigen in pancreatic intraepithelial neoplasia.Pancreas. 2003 Apr;26(3):e48-54. doi: 10.1097/00006676-200304000-00022.
• [11] MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma.J Cell Biochem. 2019 Apr;120(4):5010-5017. doi: 10.1002/jcb.27776. Epub 2018 Sep 27.
• [12] Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues.J Histochem Cytochem. 1996 Oct;44(10):1161-6. doi: 10.1177/44.10.8813081.
• [13] Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux.Ann Otol Rhinol Laryngol. 2008 Sep;117(9):688-95. doi: 10.1177/000348940811700911.
• [14] Membrane-bound (MUC1) and secretory (MUC2, MUC3, and MUC4) mucin gene expression in human lung cancer.Tumour Biol. 1996;17(3):176-92. doi: 10.1159/000217980.
• [15] Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary.J Pathol. 1997 Aug;182(4):385-91. doi: 10.1002/(SICI)1096-9896(199708)182:4<385::AID-PATH861>3.0.CO;2-Q.
• [16] Mucin gene expression in ovarian cancers.Cancer Res. 1998 Dec 1;58(23):5546-50.
• [17] Mucin phenotypic expression in early signet ring cell carcinoma of the stomach: its relationship with the clinicopathologic factors.Dig Dis Sci. 2004 Mar;49(3):417-24. doi: 10.1023/b:ddas.0000020496.98711.14.
• [18] Associations of distinct variants of the intestinal mucin gene MUC3A with ulcerative colitis and Crohn's disease.J Hum Genet. 2001;46(1):5-20. doi: 10.1007/s100380170118.
• [19] Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast.Breast J. 2001 Jan-Feb;7(1):40-5. doi: 10.1046/j.1524-4741.2001.007001040.x.
• [20] Overexpression of KIF11 in Gastric Cancer with Intestinal Mucin Phenotype.Pathobiology. 2017;84(1):16-24. doi: 10.1159/000447303. Epub 2016 Jul 27.
• [21] Expression of mucin 3 and mucin 5AC in arthritic synovial tissue.Arthritis Rheum. 2008 Jan;58(1):46-52. doi: 10.1002/art.23174.
• [22] Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas.Hum Pathol. 2001 Mar;32(3):274-81. doi: 10.1053/hupa.2001.22752.
• [23] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [24] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [25] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.