Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHN3H0A)

• DOT Name: Regulating synaptic membrane exocytosis protein 3 (RIMS3)
• Synonyms: Nim3; RIM3 gamma; Rab-3-interacting molecule 3; RIM 3
• Gene Name: RIMS3
• Related Disease: Autism
• UniProt ID: RIMS3_HUMAN
• Pfam ID: PF00168
• Sequence:
  MFNGEPGPASSGASRNVVRSSSISGEICGSQQAGGGAGTTTAKKRRSSLGAKMVAIVGLT
  QWSKSTLQLPQPEGATKKLRSNIRRSTETGIAVEMRSRVTRQGSRESTDGSTNSNSSDGT
  FIFPTTRLGAESQFSDFLDGLGPAQIVGRQTLATPPMGDVHIAIMDRSGQLEVEVIEARG
  LTPKPGSKSLPATYIKVYLLENGACLAKKKTKMTKKTCDPLYQQALLFDEGPQGKVLQVI
  VWGDYGRMDHKCFMGMAQIMLDELDLSAAVTGWYKLFPTSSVADSTLGSLTRRLSQSSLE
  SATSPSCS
• Function: Regulates synaptic membrane exocytosis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Genetic Variation	[1]

19 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 Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[18]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Regulating synaptic membrane exocytosis protein 3 (RIMS3).	[19]

References

• [1] Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca?channels.Cell Calcium. 2015 Sep;58(3):296-306. doi: 10.1016/j.ceca.2015.06.007. Epub 2015 Jun 23.
• [2] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] 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.
• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] 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.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [18] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [19] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.