Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3TXO8F)

• DOT Name: Lipase member N (LIPN)
• Synonyms: EC 3.1.1.-; Lipase-like abhydrolase domain-containing protein 4
• Gene Name: LIPN
• Related Disease:
  Autosomal recessive congenital ichthyosis 8
  Lamellar ichthyosis
  Congenital ichthyosiform erythroderma
• UniProt ID: LIPN_HUMAN
• EC Number: 3.1.1.-
• Pfam ID: PF00561
• Sequence:
  MMWLLLTTTCLICGTLNAGGFLDLENEVNPEVWMNTSEIIIYNGYPSEEYEVTTEDGYIL
  LVNRIPYGRTHARSTGPRPVVYMQHALFADNAYWLENYANGSLGFLLADAGYDVWMGNSR
  GNTWSRRHKTLSETDEKFWAFSFDEMAKYDLPGVIDFIVNKTGQEKLYFIGHSLGTTIGF
  VAFSTMPELAQRIKMNFALGPTISFKYPTGIFTRFFLLPNSIIKAVFGTKGFFLEDKKTK
  IASTKICNNKILWLICSEFMSLWAGSNKKNMNQSRMDVYMSHAPTGSSVHNILHIKQLYH
  SDEFRAYDWGNDADNMKHYNQSHPPIYDLTAMKVPTAIWAGGHDVLVTPQDVARILPQIK
  SLHYFKLLPDWNHFDFVWGLDAPQRMYSEIIALMKAYS
• Function: Plays a highly specific role in the last step of keratinocyte differentiation. May have an essential function in lipid metabolism of the most differentiated epidermal layers.
• Tissue Specificity: Highly expressed in the epidermis in the granular keratinocytes. Also detected in other tissues, although at much lower levels, including lung and spleen.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive congenital ichthyosis 8	DISJF6BI	Strong	Autosomal recessive	[1]
Lamellar ichthyosis	DIS714UN	Supportive	Autosomal recessive	[1]
Congenital ichthyosiform erythroderma	DISV8HQX	Limited	GermlineCausalMutation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lipase member N (LIPN).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Lipase member N (LIPN).	[3]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lipase member N (LIPN).	[5]

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 increases the methylation of Lipase member N (LIPN).	[4]

References

• [1] A mutation in LIPN, encoding epidermal lipase N, causes a late-onset form of autosomal-recessive congenital ichthyosis. Am J Hum Genet. 2011 Apr 8;88(4):482-7. doi: 10.1016/j.ajhg.2011.02.011.
• [2] 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.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.