Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ1GP03)

• DOT Name: Patatin-like phospholipase domain-containing protein 5 (PNPLA5)
• Synonyms: EC 3.1.1.3; GS2-like protein
• Gene Name: PNPLA5
• Related Disease:
  Familial hypercholesterolemia
  Hypercholesterolemia, familial, 1
• UniProt ID: PLPL5_HUMAN
• EC Number: 3.1.1.3
• Pfam ID: PF01734
• Sequence:
  MGFLEEEGRWNLSFSGAGYLGAHHVGATECLRQRAPRLLQGARRIYGSSSGALNAVSIVC
  GKSVDFCCSHLLGMVGQLERLSLSILHPAYAPIEHVKQQLQDALPPDAHVLASQRLGISL
  TRWPDGRNFLVTDFATCDELIQALVCTLYFPFYCGLIPPEFRGERYIDGALSNNLPFADC
  PSTITVSPFHGTVDICPQSTSPNLHELNVFNFSFQISTENFFLGLICLIPPSLEVVADNC
  RQGYLDALRFLERRGLTKEPVLWTLVSKEPPAPADGNWDAGCDQRWKGGLSLNWKVPHVQ
  VKDVPNFEQLSPELEAALKKACTRDPSRWARFWHSGPGQVLTYLLLPCTLPFEYIYFRSR
  RLVVWLPDVPADLWWMQGLLRNMALEVFSRTKAQLLGPISPPATRVLETSPLQPQIAPHR
  EELGPTHQA
• Function: Has abundant triacylglycerol lipase activity.
• Tissue Specificity: Expressed in brain and pituitary gland.
• Reactome Pathway: Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial hypercholesterolemia	DISC06IX	Strong	Genetic Variation	[1]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Patatin-like phospholipase domain-containing protein 5 (PNPLA5).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Patatin-like phospholipase domain-containing protein 5 (PNPLA5).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Patatin-like phospholipase domain-containing protein 5 (PNPLA5).	[3]

References

• [1] Genes Potentially Associated with Familial Hypercholesterolemia.Biomolecules. 2019 Nov 29;9(12):807. doi: 10.3390/biom9120807.
• [2] 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.
• [3] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [4] 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.