Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKZ3C31)

• DOT Name: Rab-like protein 3 (RABL3)
• Gene Name: RABL3
• Related Disease:
  Familial pancreatic carcinoma
  Pancreatic cancer, susceptibility to, 5
• UniProt ID: RABL3_HUMAN
• Pfam ID: PF08477
• Sequence:
  MASLDRVKVLVLGDSGVGKSSLVHLLCQNQVLGNPSWTVGCSVDVRVHDYKEGTPEEKTY
  YIELWDVGGSVGSASSVKSTRAVFYNSVNGIIFVHDLTNKKSSQNLRRWSLEALNRDLVP
  TGVLVTNGDYDQEQFADNQIPLLVIGTKLDQIHETKRHEVLTRTAFLAEDFNPEEINLDC
  TNPRYLAAGSSNAVKLSRFFDKVIEKRYFLREGNQIPGFPDRKRFGAGTLKSLHYD
• Function: Required for KRAS signaling regulation and modulation of cell proliferation. Regulator of KRAS prenylation, and probably prenylation of other small GTPases. Required for lymphocyte development and function. Not required for myeloid cell development.

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 pancreatic carcinoma	DIS1XROR	Supportive	Autosomal dominant	[1]
Pancreatic cancer, susceptibility to, 5	DISXLHFB	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Rab-like protein 3 (RABL3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rab-like protein 3 (RABL3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rab-like protein 3 (RABL3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Rab-like protein 3 (RABL3).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Rab-like protein 3 (RABL3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rab-like protein 3 (RABL3).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Rab-like protein 3 (RABL3).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Rab-like protein 3 (RABL3).	[9]

References

• [1] Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer. Nat Genet. 2019 Sep;51(9):1308-1314. doi: 10.1038/s41588-019-0475-y. Epub 2019 Aug 12.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.