Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV7L8I6)

• DOT Name: Glycoprotein endo-alpha-1,2-mannosidase (MANEA)
• Synonyms: Endo-alpha mannosidase; Endomannosidase; hEndo; EC 3.2.1.130; Mandaselin
• Gene Name: MANEA
• Related Disease:
  Anxiety disorder
  Bacterial endocarditis
  Breast cancer
  Endometriosis
  Infective endocarditis
  Mental disorder
  Panic disorder
  Polycystic ovarian syndrome
  Social phobia
  Autoimmune disease
  Advanced cancer
  Breast carcinoma
  Cocaine addiction
• UniProt ID: MANEA_HUMAN
• PDB ID: 6ZDC; 6ZDF; 6ZDK; 6ZDL; 6ZFA; 6ZFN; 6ZFQ; 6ZJ1; 6ZJ5
• EC Number: 3.2.1.130
• Pfam ID: PF16317
• Sequence:
  MAKFRRRTCIILALFILFIFSLMMGLKMLRPNTATFGAPFGLDLLPELHQRTIHLGKNFD
  FQKSDRINSETNTKNLKSVEITMKPSKASELNLDELPPLNNYLHVFYYSWYGNPQFDGKY
  IHWNHPVLEHWDPRIAKNYPQGRHNPPDDIGSSFYPELGSYSSRDPSVIETHMRQMRSAS
  IGVLALSWYPPDVNDENGEPTDNLVPTILDKAHKYNLKVTFHIEPYSNRDDQNMYKNVKY
  IIDKYGNHPAFYRYKTKTGNALPMFYVYDSYITKPEKWANLLTTSGSRSIRNSPYDGLFI
  ALLVEEKHKYDILQSGFDGIYTYFATNGFTYGSSHQNWASLKLFCDKYNLIFIPSVGPGY
  IDTSIRPWNTQNTRNRINGKYYEIGLSAALQTRPSLISITSFNEWHEGTQIEKAVPKRTS
  NTVYLDYRPHKPGLYLELTRKWSEKYSKERATYALDRQLPVS
• Tissue Specificity: Highly expressed in the liver and kidney. Expressed at lower levels in muscle, pancreas, heart, placenta, lung and brain.
• Reactome Pathway: N-glycan trimming and elongation in the cis-Golgi (R-HSA-964739)
• BioCyc Pathway: MetaCyc:HS16090-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[1]
Bacterial endocarditis	DIS920N0	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Endometriosis	DISX1AG8	Strong	Biomarker	[4]
Infective endocarditis	DIS88NSA	Strong	Biomarker	[2]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[1]
Panic disorder	DISD3VNY	Strong	Biomarker	[1]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[5]
Social phobia	DISQGN78	Strong	Biomarker	[1]
Autoimmune disease	DISORMTM	moderate	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[3]
Cocaine addiction	DISHTRXG	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Glycoprotein endo-alpha-1,2-mannosidase (MANEA) affects the response to substance of Cocaine.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[14]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase (MANEA).	[18]

References

• [1] The -endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder.Transl Psychiatry. 2014 Jan 28;4(1):e353. doi: 10.1038/tp.2013.122.
• [2] Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study.Eur Heart J. 2019 Oct 14;40(39):3222-3232. doi: 10.1093/eurheartj/ehz620.
• [3] Recombinant attenuated Salmonella typhimurium carrying a plasmid co-expressing ENDO-VEGI151 and survivin siRNA inhibits the growth of breast cancer in vivo.Mol Med Rep. 2013 Apr;7(4):1215-22. doi: 10.3892/mmr.2013.1308. Epub 2013 Feb 5.
• [4] Long-term evaluation of quality of life and gastrointestinal well-being after segmental colo-rectal resection for deep infiltrating endometriosis (ENDO-RESECT QoL).Arch Gynecol Obstet. 2020 Jan;301(1):217-228. doi: 10.1007/s00404-019-05382-8. Epub 2019 Nov 22.
• [5] Diagnostic Evaluation, Comorbidity Screening, and Treatment of Polycystic Ovary Syndrome in Adolescents in 3 Specialty Clinics.J Pediatr Adolesc Gynecol. 2018 Aug;31(4):367-371. doi: 10.1016/j.jpag.2018.01.007. Epub 2018 Feb 1.
• [6] Low-dose endosulfan inhibits proliferation and induces senescence and pro-inflammatory cytokine production in human lymphocytes, preferentially impacting cytotoxic cells.J Immunotoxicol. 2019 Dec;16(1):173-181. doi: 10.1080/1547691X.2019.1668513.
• [7] Association of variants in MANEA with cocaine-related behaviors.Arch Gen Psychiatry. 2009 Mar;66(3):267-74. doi: 10.1001/archgenpsychiatry.2008.538.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [16] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.