Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHP1DRS)

• DOT Name: RUN domain-containing protein 3A (RUNDC3A)
• Synonyms: Rap2-interacting protein 8; RPIP-8
• Gene Name: RUNDC3A
• Related Disease:
  Rectal adenocarcinoma
  Rectal carcinoma
• UniProt ID: RUN3A_HUMAN
• Pfam ID: PF02759
• Sequence:
  MEASFVQTTMALGLSSKKASSRNVAVERKNLITVCRFSVKTLLEKYTAEPIDDSSEEFVN
  FAAILEQILSHRFKACAPAGPVSWFSSDGQRGFWDYIRLACSKVPNNCVSSIENMENIST
  ARAKGRAWIRVALMEKRMSEYITTALRDTRTTRRFYDSGAIMLRDEATILTGMLIGLSAI
  DFSFCLKGEVLDGKTPVVIDYTPYLKFTQSYDYLTDEEERHSAESSTSEDNSPEHPYLPL
  VTDEDSWYSKWHKMEQKFRIVYAQKGYLEELVRLRESQLKDLEAENRRLQLQLEEAAAQN
  QREKRELEGVILELQEQLTGLIPSDHAPLAQGSKELTTPLVNQWPSLGTLNGAEGASNSK
  LYRRHSFMSTEPLSAEASLSSDSQRLGEGTRDEEPWGPIGKDPTPSMLGLCGSLASIPSC
  KSLASFKSNECLVSDSPEGSPALSPS
• Function: May act as an effector of RAP2A in neuronal cells.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rectal adenocarcinoma	DIS8R9VO	Limited	Biomarker	[1]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[1]

7 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 RUN domain-containing protein 3A (RUNDC3A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RUN domain-containing protein 3A (RUNDC3A).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of RUN domain-containing protein 3A (RUNDC3A).	[4]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of RUN domain-containing protein 3A (RUNDC3A).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of RUN domain-containing protein 3A (RUNDC3A).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RUN domain-containing protein 3A (RUNDC3A).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of RUN domain-containing protein 3A (RUNDC3A).	[10]

2 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 RUN domain-containing protein 3A (RUNDC3A).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RUN domain-containing protein 3A (RUNDC3A).	[8]

References

• [1] Identification of two novel biomarkers of rectal carcinoma progression and prognosis via co-expression network analysis.Oncotarget. 2017 Jun 27;8(41):69594-69609. doi: 10.18632/oncotarget.18646. eCollection 2017 Sep 19.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [6] 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.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.