Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4A560N)

• DOT Name: Phospholipid phosphatase-related protein type 1 (PLPPR1)
• Synonyms: Inactive 2-lysophosphatidate phosphatase PLPPR1; Lipid phosphate phosphatase-related protein type 1; Plasticity-related gene 3 protein; PRG-3
• Gene Name: PLPPR1
• Related Disease: Parkinson disease
• UniProt ID: PLPR1_HUMAN
• Pfam ID: PF01569
• Sequence:
  MAVGNNTQRSYSIIPCFIFVELVIMAGTVLLAYYFECTDTFQVHIQGFFCQDGDLMKPYP
  GTEEESFITPLVLYCVLAATPTAIIFIGEISMYFIKSTRESLIAQEKTILTGECCYLNPL
  LRRIIRFTGVFAFGLFATDIFVNAGQVVTGHLTPYFLTVCKPNYTSADCQAHHQFINNGN
  ICTGDLEVIEKARRSFPSKHAALSIYSALYATMYITSTIKTKSSRLAKPVLCLGTLCTAF
  LTGLNRVSEYRNHCSDVIAGFILGTAVALFLGMCVVHNFKGTQGSPSKPKPEDPRGVPLM
  AFPRIESPLETLSAQNHSASMTEVT
• Function: May play a role in neurite outgrowth and neurogenesis.
• Reactome Pathway: Lysosphingolipid and LPA receptors (R-HSA-419408)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[1]

8 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 Phospholipid phosphatase-related protein type 1 (PLPPR1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phospholipid phosphatase-related protein type 1 (PLPPR1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phospholipid phosphatase-related protein type 1 (PLPPR1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phospholipid phosphatase-related protein type 1 (PLPPR1).	[5]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Phospholipid phosphatase-related protein type 1 (PLPPR1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phospholipid phosphatase-related protein type 1 (PLPPR1).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Phospholipid phosphatase-related protein type 1 (PLPPR1).	[6]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Phospholipid phosphatase-related protein type 1 (PLPPR1).	[5]

References

• [1] Plasticity-related gene 3 (LPPR1) and age at diagnosis of Parkinson disease.Neurol Genet. 2018 Oct 5;4(5):e271. doi: 10.1212/NXG.0000000000000271. eCollection 2018 Oct.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.