Details of Drug Off-Target (DOT)

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

• DOT Name: LHFPL tetraspan subfamily member 2 protein (LHFPL2)
• Synonyms: Lipoma HMGIC fusion partner-like 2 protein
• Gene Name: LHFPL2
• Related Disease:
  Cardiovascular disease
  IgA nephropathy
  Brain neoplasm
  Parkinson disease
• UniProt ID: LHPL2_HUMAN
• Pfam ID: PF10242
• Sequence:
  MCHVIVTCRSMLWTLLSIVVAFAELIAFMSADWLIGKARSRGGVEPAGPGGGSPEPYHPT
  LGIYARCIRNPGVQHFQRDTLCGPYAESFGEIASGFWQATAIFLAVGIFILCMVALVSVF
  TMCVQSIMKKSIFNVCGLLQGIAGLFLILGLILYPAGWGCQKAIDYCGHYASAYKPGDCS
  LGWAFYTAIGGTVLTFICAVFSAQAEIATSSDKVQEEIEEGKNLICLL
• Function: Plays a role in female and male fertility. Involved in distal reproductive tract development.
• Tissue Specificity: Expressed in all tissues and cell lines examined except brain and peripheral blood leukocytes.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[2]
Brain neoplasm	DISY3EKS	Limited	Altered Expression	[3]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[10]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of LHFPL tetraspan subfamily member 2 protein (LHFPL2).	[14]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.PLoS One. 2014 Aug 18;9(8):e103413. doi: 10.1371/journal.pone.0103413. eCollection 2014.
• [3] Identification of genetic modifiers of age-at-onset for familial Parkinson's disease.Hum Mol Genet. 2016 Sep 1;25(17):3849-3862. doi: 10.1093/hmg/ddw206. Epub 2016 Jul 11.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.