Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK8LGAB)

• DOT Name: CTD nuclear envelope phosphatase 1 (CTDNEP1)
• Synonyms: EC 3.1.3.16; Serine/threonine-protein phosphatase dullard
• Gene Name: CTDNEP1
• Related Disease: Megalencephaly
• UniProt ID: CNEP1_HUMAN
• EC Number: 3.1.3.16
• Pfam ID: PF03031
• Sequence:
  MMRTQCLLGLRTFVAFAAKLWSFFIYLLRRQIRTVIQYQTVRYDILPLSPVSRNRLAQVK
  RKILVLDLDETLIHSHHDGVLRPTVRPGTPPDFILKVVIDKHPVRFFVHKRPHVDFFLEV
  VSQWYELVVFTASMEIYGSAVADKLDNSRSILKRRYYRQHCTLELGSYIKDLSVVHSDLS
  SIVILDNSPGAYRSHPDNAIPIKSWFSDPSDTALLNLLPMLDALRFTADVRSVLSRNLHQ
  HRLW
• Function: Serine/threonine protein phosphatase forming with CNEP1R1 an active phosphatase complex that 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. May antagonize BMP signaling.
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Megalencephaly	DISYW5SV	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[5]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[7]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CTD nuclear envelope phosphatase 1 (CTDNEP1).	[9]

References

• [1] Neurodevelopmental delays and macrocephaly in 17p13.1 microduplication syndrome.Am J Med Genet A. 2014 Nov;164A(11):2887-91. doi: 10.1002/ajmg.a.36708. Epub 2014 Aug 13.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] 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.
• [4] 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.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [7] 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.
• [8] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [9] 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.