Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOBNX6G)

• DOT Name: Endoplasmic reticulum junction formation protein lunapark (LNPK)
• Synonyms: ER junction formation factor lunapark
• Gene Name: LNPK
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Metabolic disorder
  Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum
  Triple negative breast cancer
  Intellectual disability
  Ebola virus infection
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
• UniProt ID: LNP_HUMAN
• Pfam ID: PF10058
• Sequence:
  MGGLFSRWRTKPSTVEVLESIDKEIQALEEFREKNQRLQKLWVGRLILYSSVLYLFTCLI
  VYLWYLPDEFTARLAMTLPFFAFPLIIWSIRTVIIFFFSKRTERNNEALDDLKSQRKKIL
  EEVMEKETYKTAKLILERFDPDSKKAKECEPPSAGAAVTARPGQEIRQRTAAQRNLSPTP
  ASPNQGPPPQVPVSPGPPKDSSAPGGPPERTVTPALSSNVLPRHLGSPATSVPGMGLHPP
  GPPLARPILPRERGALDRIVEYLVGDGPQNRYALICQQCFSHNGMALKEEFEYIAFRCAY
  CFFLNPARKTRPQAPRLPEFSFEKRQVVEGSSSVGPLPSGSVLSSDNQFNEESLEHDVLD
  DNTEQTDDKIPATEQTNQVIEKASDSEEPEEKQETENEEASVIETNSTVPGADSIPDPEL
  SGESLTAE
• Function: Endoplasmic reticulum (ER)-shaping membrane protein that plays a role in determining ER morphology. Involved in the stabilization of nascent three-way ER tubular junctions within the ER network. May also play a role as a curvature-stabilizing protein within the three-way ER tubular junction network. May be involved in limb development. Is involved in central nervous system development.
• Tissue Specificity: Expressed in neural precursor cells, where it is detected at the growth-cone-like structure and branching sites of neurite-like processes.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[2]
Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	DISUVM1Q	Strong	Autosomal recessive	[3]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[4]
Intellectual disability	DISMBNXP	moderate	Biomarker	[3]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[6]
Lung cancer	DISCM4YA	Limited	Altered Expression	[7]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[7]

8 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 Endoplasmic reticulum junction formation protein lunapark (LNPK).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[13]

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 decreases the methylation of Endoplasmic reticulum junction formation protein lunapark (LNPK).	[14]

References

• [1] High mRNA expression of splice variant SYK short correlates with hepatic disease progression in chemonaive lymph node negative colon cancer patients.PLoS One. 2017 Sep 28;12(9):e0185607. doi: 10.1371/journal.pone.0185607. eCollection 2017.
• [2] Effects of imidazoline-like drugs on liver and adipose tissues, and their role in preventing obesity and associated cardio-metabolic disorders.Int J Obes (Lond). 2019 Nov;43(11):2163-2175. doi: 10.1038/s41366-019-0342-z. Epub 2019 Mar 29.
• [3] Mutations in LNPK, Encoding the Endoplasmic Reticulum Junction Stabilizer Lunapark, Cause a Recessive Neurodevelopmental Syndrome. Am J Hum Genet. 2018 Aug 2;103(2):296-304. doi: 10.1016/j.ajhg.2018.06.011. Epub 2018 Jul 19.
• [4] Systemic Administration of siRNA with Anti-HB-EGF Antibody-Modified Lipid Nanoparticles for the Treatment of Triple-Negative Breast Cancer.Mol Pharm. 2018 Apr 2;15(4):1495-1504. doi: 10.1021/acs.molpharmaceut.7b01055. Epub 2018 Mar 12.
• [5] Emerging targets and novel approaches to Ebola virus prophylaxis and treatment.BioDrugs. 2013 Dec;27(6):565-83. doi: 10.1007/s40259-013-0046-1.
• [6] Lipid nanoparticles that deliver IL-12 messenger RNA suppress tumorigenesis in MYC oncogene-driven hepatocellular carcinoma.J Immunother Cancer. 2018 Nov 20;6(1):125. doi: 10.1186/s40425-018-0431-x.
• [7] Antitumor activity of kinetochore-associated protein 2 siRNA against lung cancer patient-derived tumor xenografts.Oncol Lett. 2018 Apr;15(4):4676-4682. doi: 10.3892/ol.2018.7890. Epub 2018 Jan 29.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] 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.
• [11] 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.
• [12] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [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] 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.
• [15] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.