Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0A5YKR)

• DOT Name: Ras-like protein family member 10B (RASL10B)
• Synonyms: EC 3.6.5.2; Ras-like protein VTS58635; Ras-related protein 17; RRP17
• Gene Name: RASL10B
• Related Disease: Polycystic ovarian syndrome
• UniProt ID: RSLAB_HUMAN
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MVSTYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTARRLYLPAVVMNGHVHDLQILDF
  PPISAFPVNTLQEWADTCCRGLRSVHAYILVYDICCFDSFEYVKTIRQQILETRVIGTSE
  TPIIIVGNKRDLQRGRVIPRWNVSHLVRKTWKCGYVECSAKYNWHILLLFSELLKSVGCA
  RCKHVHAALRFQGALRRNRCAIM
• Function: May facilitate the release of atrial natriuretic peptide by cardiomyocytes and hence play a role in the regulation of arterial pressure.
• Tissue Specificity: Expressed at high levels in skeletal muscle and, at much lower levels, in heart, brain and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[1]

9 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 Ras-like protein family member 10B (RASL10B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-like protein family member 10B (RASL10B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-like protein family member 10B (RASL10B).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ras-like protein family member 10B (RASL10B).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras-like protein family member 10B (RASL10B).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-like protein family member 10B (RASL10B).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-like protein family member 10B (RASL10B).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-like protein family member 10B (RASL10B).	[10]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Ras-like protein family member 10B (RASL10B).	[11]

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 decreases the methylation of Ras-like protein family member 10B (RASL10B).	[7]

References

• [1] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [9] 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.
• [10] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [11] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.