Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEXTN6I)

• DOT Name: Ras-like protein family member 10A (RASL10A)
• Synonyms: EC 3.6.5.2; Ras-like protein RRP22; Ras-related protein on chromosome 22
• Gene Name: RASL10A
• Related Disease:
  Adult glioblastoma
  Astrocytoma
  Glioblastoma multiforme
  Malignant glioma
  Neoplasm
• UniProt ID: RSLAA_HUMAN
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MGGSLRVAVLGAPGVGKTAIIRQFLFGDYPERHRPTDGPRLYRPAVLLDGAVYDLSIRDG
  DVAGPGSSPGGPEEWPDAKDWSLQDTDAFVLVYDICSPDSFDYVKALRQRIAETRPAGAP
  EAPILVVGNKRDRQRLRFGPRRALAALVRRGWRCGYLECSAKYNWHVLRLFRELLRCALV
  RARPAHPALRLQGALHPARCSLM
• Function: Potent inhibitor of cellular proliferation.
• Tissue Specificity: Expression appears to be strictly limited to the central nervous system.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Astrocytoma	DISL3V18	Strong	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	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 increases the expression of Ras-like protein family member 10A (RASL10A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-like protein family member 10A (RASL10A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ras-like protein family member 10A (RASL10A).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Ras-like protein family member 10A (RASL10A).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ras-like protein family member 10A (RASL10A).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ras-like protein family member 10A (RASL10A).	[6]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Ras-like protein family member 10A (RASL10A).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-like protein family member 10A (RASL10A).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-like protein family member 10A (RASL10A).	[12]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Ras-like protein family member 10A (RASL10A).	[9]

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 Ras-like protein family member 10A (RASL10A).	[10]

References

• [1] DNA hypermethylation and histone modifications downregulate the candidate tumor suppressor gene RRP22 on 22q12 in human gliomas.Brain Pathol. 2012 Jan;22(1):17-25. doi: 10.1111/j.1750-3639.2011.00507.x. Epub 2011 Aug 16.
• [2] RRP22: a novel neural tumor suppressor for astrocytoma.Med Oncol. 2012 Mar;29(1):332-9. doi: 10.1007/s12032-010-9795-6. Epub 2011 Jan 25.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [8] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [9] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [10] 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.
• [11] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [12] 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.