Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9AYVGV)

• DOT Name: RING finger protein 207 (RNF207)
• Gene Name: RNF207
• Related Disease:
  Acute myocardial infarction
  Long QT syndrome
• UniProt ID: RN207_HUMAN
• Pfam ID: PF00643 ; PF00097
• Sequence:
  MSGAIFGPLEGPSSLDAPSIHPLVCPLCHVQYERPCLLDCFHDFCAGCLRGRATDGRLTC
  PLCQHQTVLKGPSGLPPVDRLLQFLVDSSGDGVEAVRCANCDLECSEQDVETTYFCNTCG
  QPLCARCRDETHRARMFARHDIVALGQRSRDVPQKCTLHAEPYLLFSTDKKLLLCIRCFR
  DMQKESRAHCVDLESAYVQGCERLEQAVLAVKALQTATREAIALLQAMVEEVRHSAAEEE
  DAIHALFGSMQDRLAERKALLLQAVQSQYEEKDKAFKEQLSHLATLLPTLQVHLVICSSF
  LSLANKAEFLDLGYELMERLQGIVTRPHHLRPIQSSKIASDHRAEFARCLEPLLLLGPRR
  VAAAASGANTLAGGLGPKALTGPHCPSPVGKMSGSPVQKPTLHRSISTKVLLAEGENTPF
  AEHCRHYEDSYRHLQAEMQSLKDQVQELHRDLTKHHSLIKAEIMGDVLHKSLQLDVQIAS
  EHASLEGMRVVFQEIWEEAYQRVANEQEIYEAQLHDLLQLRQENAYLTTITKQITPYVRS
  IAKVKERLEPRFQAPVDEQSESLQNTHDDSRNNAASARNNPGSVPEKREKTSEPKGNSWA
  PNGLSEEPLLKNMDHHRSKQKNGGDVPTWREHPT
• Function: Plays a role in cardiac repolarization possibly by stabilizing membrane expression of the potassium channel KCNH2/HERG, or by assisting its synthesis, folding or export from the endoplasmic reticulum, in a heat shock protein-dependent manner.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Long QT syndrome	DISMKWS3	Limited	Autosomal dominant	[2]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of RING finger protein 207 (RNF207).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of RING finger protein 207 (RNF207).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RING finger protein 207 (RNF207).	[10]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RING finger protein 207 (RNF207).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RING finger protein 207 (RNF207).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RING finger protein 207 (RNF207).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of RING finger protein 207 (RNF207).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of RING finger protein 207 (RNF207).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of RING finger protein 207 (RNF207).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RING finger protein 207 (RNF207).	[12]

References

• [1] Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute myocardial infarction.Clin Sci (Lond). 2015 Jun;128(11):751-60. doi: 10.1042/CS20140663.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] 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.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] 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.
• [12] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.