Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW4LHU8)

• DOT Name: RILP-like protein 1 (RILPL1)
• Synonyms: Rab-interacting lysosomal-like protein 1
• Gene Name: RILPL1
• Related Disease: Oculopharyngodistal myopathy 4
• UniProt ID: RIPL1_HUMAN
• Pfam ID: PF09744 ; PF11461
• Sequence:
  MEEERGSALAAESALEKNVAELTVMDVYDIASLVGHEFERVIDQHGCEAIARLMPKVVRV
  LEILEVLVSRHHVAPELDELRLELDRLRLERMDRIEKERKHQKELELVEDVWRGEAQDLL
  SQIAQLQEENKQLMTNLSHKDVNFSEEEFQKHEGMSERERQVMKKLKEVVDKQRDEIRAK
  DRELGLKNEDVEALQQQQTRLMKINHDLRHRVTVVEAQGKALIEQKVELEADLQTKEQEM
  GSLRAELGKLRERLQGEHSQNGEEEPETEPVGEESISDAEKVAMDLKDPNRPRFTLQELR
  DVLHERNELKSKVFLLQEELAYYKSEEMEEENRIPQPPPIAHPRTSPQPESGIKRLFSFF
  SRDKKRLANTQRNVHIQESFGQWANTHRDDGYTEQGQEALQHL
• Function: Plays a role in the regulation of cell shape and polarity. Plays a role in cellular protein transport, including protein transport away from primary cilia. Neuroprotective protein, which acts by sequestring GAPDH in the cytosol and prevent the apoptotic function of GAPDH in the nucleus. Competes with SIAH1 for binding GAPDH. Does not regulate lysosomal morphology and distribution. Binds to RAB10 following LRRK2-mediated RAB10 phosphorylation which leads to inhibition of ciliogenesis.
• Tissue Specificity: Widely expressed. Expressed at lower level in liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oculopharyngodistal myopathy 4	DISCLZYV	Limited	Autosomal dominant	[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 RILP-like protein 1 (RILPL1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of RILP-like protein 1 (RILPL1).	[7]

7 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 RILP-like protein 1 (RILPL1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RILP-like protein 1 (RILPL1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of RILP-like protein 1 (RILPL1).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of RILP-like protein 1 (RILPL1).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of RILP-like protein 1 (RILPL1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RILP-like protein 1 (RILPL1).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of RILP-like protein 1 (RILPL1).	[9]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] 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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [8] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [9] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.