Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT351FKB)

• DOT Name: Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1)
• Synonyms: ER-Golgi intermediate compartment 32 kDa protein; ERGIC-32
• Gene Name: ERGIC1
• Related Disease:
  Myocardial infarction
  Arthrogryposis
  Inflammatory bowel disease
  Prostate cancer
  Arthrogryposis multiplex congenita 2, neurogenic type
  Amyotrophic lateral sclerosis
  Frontotemporal dementia
  Gastric cancer
  Stomach cancer
• UniProt ID: ERGI1_HUMAN
• Pfam ID: PF07970 ; PF13850
• Sequence:
  MPFDFRRFDIYRKVPKDLTQPTYTGAIISICCCLFILFLFLSELTGFITTEVVNELYVDD
  PDKDSGGKIDVSLNISLPNLHCELVGLDIQDEMGRHEVGHIDNSMKIPLNNGAGCRFEGQ
  FSINKVPGNFHVSTHSATAQPQNPDMTHVIHKLSFGDTLQVQNIHGAFNALGGADRLTSN
  PLASHDYILKIVPTVYEDKSGKQRYSYQYTVANKEYVAYSHTGRIIPAIWFRYDLSPITV
  KYTERRQPLYRFITTICAIIGGTFTVAGILDSCIFTASEAWKKIQLGKMH
• Function: Possible role in transport between endoplasmic reticulum and Golgi.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[1]
Arthrogryposis	DISC81CM	moderate	Genetic Variation	[2]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[3]
Prostate cancer	DISF190Y	moderate	Biomarker	[4]
Arthrogryposis multiplex congenita 2, neurogenic type	DISV5DEN	Supportive	Autosomal recessive	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[5]
Frontotemporal dementia	DISKYHXL	Limited	Genetic Variation	[5]
Gastric cancer	DISXGOUK	Limited	Biomarker	[6]
Stomach cancer	DISKIJSX	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1) increases the Neutropenia ADR of Chlorothiazide.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Endoplasmic reticulum-Golgi intermediate compartment protein 1 (ERGIC1).	[14]

References

• [1] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [2] Mutations in ERGIC1 cause Arthrogryposis multiplex congenita, neuropathic type. Clin Genet. 2018 Jan;93(1):160-163. doi: 10.1111/cge.13018. Epub 2017 Jul 26.
• [3] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [4] High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer.PLoS One. 2012;7(6):e39801. doi: 10.1371/journal.pone.0039801. Epub 2012 Jun 28.
• [5] Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum.JAMA Neurol. 2018 Jul 1;75(7):860-875. doi: 10.1001/jamaneurol.2018.0372.
• [6] Differential Expression and Significance of Endoplasmic Reticulum Golgi Intermediate Compartment 1 in Precancerous Gastric Lesions and Gastric Cancer.Am J Med Sci. 2018 Mar;355(3):228-234. doi: 10.1016/j.amjms.2017.11.001. Epub 2017 Nov 9.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] 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.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] 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.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [17] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [18] 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.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.