Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQYZ3LQ)

• DOT Name: RNA-binding protein 12 (RBM12)
• Synonyms: RNA-binding motif protein 12; SH3/WW domain anchor protein in the nucleus; SWAN
• Gene Name: RBM12
• Related Disease:
  Schizoaffective disorder
  Schizophrenia
• UniProt ID: RBM12_HUMAN
• PDB ID: 1WEL; 2CPY; 2DNN; 2EK1; 2EK6
• Pfam ID: PF00076
• Sequence:
  MAVVIRLQGLPIVAGTMDIRHFFSGLTIPDGGVHIVGGELGEAFIVFATDEDARLGMMRT
  GGTIKGSKVTLLLSSKTEMQNMIELSRRRFETANLDIPPANASRSGPPPSSGMSSRVNLP
  TTVSNFNNPSPSVVTATTSVHESNKNIQTFSTASVGTAPPNMGASFGSPTFSSTVPSTAS
  PMNTVPPPPIPPIPAMPSLPPMPSIPPIPVPPPVPTLPPVPPVPPIPPVPSVPPMTPLPP
  MSGMPPLNPPPVAPLPAGMNGSGAPMNLNNNLNPMFLGPLNPVNPIQMNSQSSVKPLPIN
  PDDLYVSVHGMPFSAMENDVRDFFHGLRVDAVHLLKDHVGRNNGNGLVKFLSPQDTFEAL
  KRNRMLMIQRYVEVSPATERQWVAAGGHITFKQNMGPSGQTHPPPQTLPRSKSPSGQKRS
  RSRSPHEAGFCVYLKGLPFEAENKHVIDFFKKLDIVEDSIYIAYGPNGKATGEGFVEFRN
  EADYKAALCRHKQYMGNRFIQVHPITKKGMLEKIDMIRKRLQNFSYDQREMILNPEGDVN
  SAKVCAHITNIPFSITKMDVLQFLEGIPVDENAVHVLVDNNGQGLGQALVQFKNEDDARK
  SERLHRKKLNGREAFVHVVTLEDMREIEKNPPAQGKKGLKMPVPGNPAVPGMPNAGLPGV
  GLPSAGLPGAGLPSTGLPGSAITSAGLPGAGMPSAGIPSAGGEEHAFLTVGSKEANNGPP
  FNFPGNFGGSNAFGPPIPPPGLGGGAFGDARPGMPSVGNSGLPGLGLDVPGFGGGPNNLS
  GPSGFGGGPQNFGNGPGSLGGPPGFGSGPPGLGSAPGHLGGPPAFGPGPGPGPGPGPIHI
  GGPPGFASSSGKPGPTVIKVQNMPFTVSIDEILDFFYGYQVIPGSVCLKYNEKGMPTGEA
  MVAFESRDEATAAVIDLNDRPIGSRKVKLVLG

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizoaffective disorder	DISLBW6B	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

14 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 RNA-binding protein 12 (RBM12).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA-binding protein 12 (RBM12).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RNA-binding protein 12 (RBM12).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RNA-binding protein 12 (RBM12).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of RNA-binding protein 12 (RBM12).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of RNA-binding protein 12 (RBM12).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of RNA-binding protein 12 (RBM12).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of RNA-binding protein 12 (RBM12).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of RNA-binding protein 12 (RBM12).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of RNA-binding protein 12 (RBM12).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein 12 (RBM12).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of RNA-binding protein 12 (RBM12).	[7]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of RNA-binding protein 12 (RBM12).	[13]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of RNA-binding protein 12 (RBM12).	[14]

References

• [1] Truncating mutations in RBM12 are associated with psychosis.Nat Genet. 2017 Aug;49(8):1251-1254. doi: 10.1038/ng.3894. Epub 2017 Jun 19.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [13] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [14] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.