Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMHZ1WP)

• DOT Name: Vesicle-associated membrane protein 1
• Synonyms: VAMP-1; Synaptobrevin-1
• Gene Name: VAMP1
• Related Disease:
  Myasthenic syndrome, congenital, 25, presynaptic
  Spastic ataxia 1
  Obsolete presynaptic congenital myasthenic syndrome
• UniProt ID: VAMP1_HUMAN
• Pfam ID: PF00957
• Sequence:
  MSAPAQPPAEGTEGTAPGGGPPGPPPNMTSNRRLQQTQAQVEEVVDIIRVNVDKVLERDQ
  KLSELDDRADALQAGASQFESSAAKLKRKYWWKNCKMMIMLGAICAIIVVVIVIYFFT
• Function: Involved in the targeting and/or fusion of transport vesicles to their target membrane.
• Tissue Specificity: Nervous system, skeletal muscle and adipose tissue.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway:
  Toxicity of botulinum toxin type F (botF) (R-HSA-5250981)
  Toxicity of botulinum toxin type G (botG) (R-HSA-5250989)
  Toxicity of botulinum toxin type D (botD) (R-HSA-5250955)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myasthenic syndrome, congenital, 25, presynaptic	DIS3TY1U	Strong	Autosomal recessive	[1]
Spastic ataxia 1	DISUKK0J	Strong	Autosomal dominant	[2]
Obsolete presynaptic congenital myasthenic syndrome	DISCATK3	Supportive	Autosomal dominant	[3]

9 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 Vesicle-associated membrane protein 1.	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Vesicle-associated membrane protein 1.	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Vesicle-associated membrane protein 1.	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Vesicle-associated membrane protein 1.	[7]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Vesicle-associated membrane protein 1.	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Vesicle-associated membrane protein 1.	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Vesicle-associated membrane protein 1.	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Vesicle-associated membrane protein 1.	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Vesicle-associated membrane protein 1.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Vesicle-associated membrane protein 1.	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Vesicle-associated membrane protein 1.	[14]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families. Am J Hum Genet. 2012 Sep 7;91(3):548-52. doi: 10.1016/j.ajhg.2012.07.018.
• [3] Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome. Ann Neurol. 2017 Apr;81(4):597-603. doi: 10.1002/ana.24905. Epub 2017 Mar 29.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] 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.
• [7] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [8] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.