Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH6C9TY)

• DOT Name: Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1)
• Synonyms: NEP1-R1; Transmembrane protein 188
• Gene Name: CNEP1R1
• UniProt ID: NEPR1_HUMAN
• Pfam ID: PF09771
• Sequence:
  MNSLEQAEDLKAFERRLTEYIHCLQPATGRWRMLLIVVSVCTATGAWNWLIDPETQKVSF
  FTSLWNHPFFTISCITLIGLFFAGIHKRVVAPSIIAARCRTVLAEYNMSCDDTGKLILKP
  RPHVQ
• Function: Forms with the serine/threonine protein phosphatase CTDNEP1 an active complex which dephosphorylates and may activate LPIN1 and LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol.
• Tissue Specificity: Muscle specific with lower expression in other metabolic tissues.
• Reactome Pathway: Depolymerization of the Nuclear Lamina (R-HSA-4419969)

Molecular Interaction Atlas (MIA) of This DOT

9 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 Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[10]

1 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 Nuclear envelope phosphatase-regulatory subunit 1 (CNEP1R1).	[6]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.