Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNAK9X4)

• DOT Name: Ras-like protein family member 12 (RASL12)
• Synonyms: EC 3.6.5.2; Ras-like protein Ris
• Gene Name: RASL12
• Related Disease:
  Rheumatoid arthritis
  Chronic kidney disease
  Gastroesophageal reflux disease
  Multiple sclerosis
  Neuromyelitis optica
  Optic neuritis
  Schizophrenia
• UniProt ID: RASLC_HUMAN
• PDB ID: 3C5C
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MSSVFGKPRAGSGPQSAPLEVNLAILGRRGAGKSALTVKFLTKRFISEYDPNLEDTYSSE
  ETVDHQPVHLRVMDTADLDTPRNCERYLNWAHAFLVVYSVDSRQSFDSSSSYLELLALHA
  KETQRSIPALLLGNKLDMAQYRQVTKAEGVALAGRFGCLFFEVSACLDFEHVQHVFHEAV
  REARRELEKSPLTRPLFISEERALPHQAPLTARHGLASCTFNTLSTINLKEMPTVAQAKL
  VTVKSSRAQSKRKAPTLTLLKGFKIF

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[2]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Neuromyelitis optica	DISBFGKL	Strong	Genetic Variation	[5]
Optic neuritis	DISDYCHC	Strong	Genetic Variation	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[6]

13 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 12 (RASL12).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Ras-like protein family member 12 (RASL12).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Ras-like protein family member 12 (RASL12).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ras-like protein family member 12 (RASL12).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ras-like protein family member 12 (RASL12).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ras-like protein family member 12 (RASL12).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ras-like protein family member 12 (RASL12).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ras-like protein family member 12 (RASL12).	[13]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Ras-like protein family member 12 (RASL12).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras-like protein family member 12 (RASL12).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras-like protein family member 12 (RASL12).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-like protein family member 12 (RASL12).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-like protein family member 12 (RASL12).	[18]

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 12 (RASL12).	[16]

References

• [1] Effects of once-monthly minodronate versus risedronate in osteoporosis patients with rheumatoid arthritis: a 12-month randomized head-to-head comparison.Osteoporos Int. 2018 Jul;29(7):1637-1642. doi: 10.1007/s00198-018-4494-9. Epub 2018 Mar 24.
• [2] Efficacy and safety of once-monthly risedronate in osteoporosis subjects with mild-to-moderate chronic kidney disease: a post hoc subgroup analysis of a phase III trial in Japan.J Bone Miner Metab. 2019 Jul;37(4):730-740. doi: 10.1007/s00774-018-0977-1. Epub 2018 Dec 6.
• [3] Correlation between the reflux finding score and the GERD impact scale in patients with gastroesophageal reflux disease.J Biol Regul Homeost Agents. 2018 Jul-Aug;32(4):989-993.
• [4] Does the radiologically isolated syndrome exist? A dual-task cost pilot study.Neurol Sci. 2017 Nov;38(11):2007-2013. doi: 10.1007/s10072-017-3094-3. Epub 2017 Aug 22.
• [5] The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review.J Autoimmun. 2014 Feb-Mar;48-49:134-42. doi: 10.1016/j.jaut.2014.01.022. Epub 2014 Feb 10.
• [6] Effects of Continuing Oral Risperidone vs. Switching from Risperidone to Risperidone Long-Acting Injection on Cognitive Function in Stable Schizophrenia Patients: A Pilot Study.Front Psychiatry. 2018 Mar 8;9:74. doi: 10.3389/fpsyt.2018.00074. eCollection 2018.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] 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.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.
• [17] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.