Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT99MBGB)

• DOT Name: Mannosyl-oligosaccharide glucosidase (MOGS)
• Synonyms: EC 3.2.1.106; Processing A-glucosidase I
• Gene Name: MOGS
• Related Disease:
  Malaria
  MOGS-congenital disorder of glycosylation
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Chromosomal disorder
  Cystic fibrosis
  Dengue
  Hamartoma
  Lung cancer
  Lung carcinoma
  Melanoma
  RFT1-congenital disorder of glycosylation
  SRD5A3-congenital disorder of glycosylation
  Turner syndrome
  Zika virus infection
  Congenital disorder of glycosylation
  Obesity
  Holoprosencephaly
  Chronic myelomonocytic leukaemia
  Chronic myelomonocytic leukemia
  Neoplasm
• UniProt ID: MOGS_HUMAN
• EC Number: 3.2.1.106
• Pfam ID: PF03200 ; PF16923
• Sequence:
  MARGERRRRAVPAEGVRTAERAARGGPGRRDGRGGGPRSTAGGVALAVVVLSLALGMSGR
  WVLAWYRARRAVTLHSAPPVLPADSSSPAVAPDLFWGTYRPHVYFGMKTRSPKPLLTGLM
  WAQQGTTPGTPKLRHTCEQGDGVGPYGWEFHDGLSFGRQHIQDGALRLTTEFVKRPGGQH
  GGDWSWRVTVEPQDSGTSALPLVSLFFYVVTDGKEVLLPEVGAKGQLKFISGHTSELGDF
  RFTLLPPTSPGDTAPKYGSYNVFWTSNPGLPLLTEMVKSRLNSWFQHRPPGAPPERYLGL
  PGSLKWEDRGPSGQGQGQFLIQQVTLKIPISIEFVFESGSAQAGGNQALPRLAGSLLTQA
  LESHAEGFRERFEKTFQLKEKGLSSGEQVLGQAALSGLLGGIGYFYGQGLVLPDIGVEGS
  EQKVDPALFPPVPLFTAVPSRSFFPRGFLWDEGFHQLVVQRWDPSLTREALGHWLGLLNA
  DGWIGREQILGDEARARVPPEFLVQRAVHANPPTLLLPVAHMLEVGDPDDLAFLRKALPR
  LHAWFSWLHQSQAGPLPLSYRWRGRDPALPTLLNPKTLPSGLDDYPRASHPSVTERHLDL
  RCWVALGARVLTRLAEHLGEAEVAAELGPLAASLEAAESLDELHWAPELGVFADFGNHTK
  AVQLKPRPPQGLVRVVGRPQPQLQYVDALGYVSLFPLLLRLLDPTSSRLGPLLDILADSR
  HLWSPFGLRSLAASSSFYGQRNSEHDPPYWRGAVWLNVNYLALGALHHYGHLEGPHQARA
  AKLHGELRANVVGNVWRQYQATGFLWEQYSDRDGRGMGCRPFHGWTSLVLLAMAEDY
• Function: In the context of N-glycan degradation, cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Metabolic pathways (hsa01100)
  Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  N-glycan trimming in the ER and Calnexin/Calreticulin cycle (R-HSA-532668)
  Maturation of spike protein (R-HSA-9683686)
  Maturation of spike protein (R-HSA-9694548)
  Defective MOGS causes CDG-2b (R-HSA-4793954)
• BioCyc Pathway: MetaCyc:HS03863-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
MOGS-congenital disorder of glycosylation	DISKRRTD	Definitive	Autosomal recessive	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[4]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[5]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[6]
Dengue	DISKH221	Strong	Biomarker	[7]
Hamartoma	DIS0I87H	Strong	Genetic Variation	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Melanoma	DIS1RRCY	Strong	Biomarker	[10]
RFT1-congenital disorder of glycosylation	DISA78DX	Strong	Genetic Variation	[11]
SRD5A3-congenital disorder of glycosylation	DISGHPPC	Strong	Autosomal recessive	[12]
Turner syndrome	DIS2035C	Strong	Biomarker	[13]
Zika virus infection	DISQUCTY	Strong	Biomarker	[14]
Congenital disorder of glycosylation	DIS400QP	moderate	Genetic Variation	[15]
Obesity	DIS47Y1K	moderate	Biomarker	[16]
Holoprosencephaly	DISR35EC	Disputed	Genetic Variation	[17]
Chronic myelomonocytic leukaemia	DISDN5P7	Limited	Genetic Variation	[4]
Chronic myelomonocytic leukemia	DISIL8UR	Limited	Biomarker	[18]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[23]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[24]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mannosyl-oligosaccharide glucosidase (MOGS).	[29]

References

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• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Isodicentric Philadelphia chromosome in acute lymphoblastic leukemia with der(7;12)(q10;q10).Leuk Res. 2007 May;31(5):713-8. doi: 10.1016/j.leukres.2006.05.023. Epub 2006 Sep 18.
• [4] Donor cell-derived acute myeloblastic leukemia after allogeneic peripheral blood hematopoietic stem cell transplantation for juvenile myelomonocytic leukemia.J Pediatr Hematol Oncol. 2006 Nov;28(11):763-7. doi: 10.1097/01.mph.0000243660.48808.72.
• [5] Recessive cancer genes in meningiomas? An analysis of 31 cases.Cancer Genet Cytogenet. 1987 Jul;27(1):145-59. doi: 10.1016/0165-4608(87)90269-x.
• [6] Two rearranged MET alleles in MNNG-HOS cells reveal the orientation of MET on chromosome 7 to other markers tightly linked to the cystic fibrosis locus.Proc Natl Acad Sci U S A. 1988 Apr;85(8):2667-71. doi: 10.1073/pnas.85.8.2667.
• [7] Enhancing the antiviral potency of ER -glucosidase inhibitor IHVR-19029 against hemorrhagic fever viruses in vitro and in vivo.Antiviral Res. 2018 Feb;150:112-122. doi: 10.1016/j.antiviral.2017.12.008. Epub 2017 Dec 15.
• [8] A hamartoma of the breast with an aberration of 12q mapped to the MAR region by fluorescence in situ hybridization.Cancer Genet Cytogenet. 1995 Oct 1;84(1):82-4. doi: 10.1016/0165-4608(95)00060-7.
• [9] Carboplatin AUC and gamma-glutamylcysteine synthetase gene expression in peripheral mononuclear cells of lung cancer patients.Anticancer Res. 2001 Nov-Dec;21(6A):3933-6.
• [10] Cytologic characterization of two distinct alpha satellite DNA domains on human chromosome 7, using double-labeling hybridizations in fluorescence and electron microscopy on a melanoma cell line.Cancer Genet Cytogenet. 1997 Jul 1;96(1):17-22. doi: 10.1016/s0165-4608(96)00282-8.
• [11] Mitotic Intragenic Recombination: A Mechanism of Survival for Several Congenital Disorders of Glycosylation.Am J Hum Genet. 2016 Feb 4;98(2):339-46. doi: 10.1016/j.ajhg.2015.12.007. Epub 2016 Jan 21.
• [12] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [13] Paternally derived der(7)t(Y;7)(p11.1 approximately 11.2;p22.3)dn in a mosaic case with Turner syndrome.Eur J Med Genet. 2009 Jul-Aug;52(4):207-10. doi: 10.1016/j.ejmg.2009.03.016. Epub 2009 Apr 16.
• [14] Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens.J Cell Biol. 2017 Mar 6;216(3):571-581. doi: 10.1083/jcb.201610093. Epub 2017 Jan 30.
• [15] Compound heterozygous variants in MOGS inducing congenital disorders of glycosylation (CDG) IIb.J Hum Genet. 2019 Mar;64(3):265-268. doi: 10.1038/s10038-018-0552-6. Epub 2018 Dec 26.
• [16] p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.FASEB J. 2018 Jul;32(7):3892-3902. doi: 10.1096/fj.201701004RR. Epub 2018 Feb 20.
• [17] Prenatal diagnosis of holoprosencephaly in two fetuses with der (7)t(1;7)(q32;q32)pat inherited from the father with double translocations.Prenat Diagn. 2003 Feb;23(2):134-7. doi: 10.1002/pd.552.
• [18] An unusual cytogenetic abnormality involving chromosomes 1 and 7 in a case of chronic myelomonocytic leukemia.Cancer Genet Cytogenet. 1995 Nov;85(1):75-7. doi: 10.1016/0165-4608(95)00139-5.
• [19] A comprehensive karyotypic analysis on a newly developed hepatocellular carcinoma cell line, HKCI-1, by spectral karyotyping and comparative genomic hybridization.Cancer Genet Cytogenet. 2000 Aug;121(1):9-16. doi: 10.1016/s0165-4608(99)00247-2.
• [20] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [21] 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.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [24] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [25] 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.
• [26] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [27] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [28] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [29] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.