Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKQC813)

• DOT Name: Ran guanine nucleotide release factor (RANGRF)
• Synonyms: RanGNRF; Ran-binding protein MOG1
• Gene Name: RANGRF
• Related Disease:
  Arrhythmia
  Lung adenocarcinoma
  Paroxysmal familial ventricular fibrillation
  Brugada syndrome
• UniProt ID: MOG1_HUMAN
• PDB ID: 5YFG
• Pfam ID: PF04603
• Sequence:
  MEPTRDCPLFGGAFSAILPMGAIDVSDLRPVPDNQEVFCHPVTDQSLIVELLELQAHVRG
  EAAARYHFEDVGGVQGARAVHVESVQPLSLENLALRGRCQEAWVLSGKQQIAKENQQVAK
  DVTLHQALLRLPQYQTDLLLTFNQPPPDNRSSLGPENLSPAPWSLGDFEQLVTSLTLHDP
  NIFGPQ
• Function: May regulate the intracellular trafficking of RAN. Promotes guanine nucleotide release from RAN and inhibits binding of new GTP by preventing the binding of the RAN guanine nucleotide exchange factor RCC1. Regulates the levels of GTP-bound RAN in the nucleus, and thereby plays a role in the regulation of RAN-dependent mitotic spindle dynamics. Enhances the expression of SCN5A at the cell membrane in cardiomyocytes.
• Tissue Specificity: Isoform 1 and isoform 2 are ubiquitously expressed . Detected in heart and brain .
• Reactome Pathway: Phase 0 - rapid depolarisation (R-HSA-5576892)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arrhythmia	DISFF2NI	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]
Paroxysmal familial ventricular fibrillation	DISRM7IX	Strong	Biomarker	[3]
Brugada syndrome	DISSGN0E	Disputed	Autosomal dominant	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ran guanine nucleotide release factor (RANGRF).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ran guanine nucleotide release factor (RANGRF).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ran guanine nucleotide release factor (RANGRF).	[7]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Ran guanine nucleotide release factor (RANGRF).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ran guanine nucleotide release factor (RANGRF).	[10]

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 Ran guanine nucleotide release factor (RANGRF).	[8]

References

• [1] Functional prediction of miR-3144-5p in human cardiac myocytes based on transcriptome sequencing and bioinformatics.Medicine (Baltimore). 2017 Aug;96(32):e7539. doi: 10.1097/MD.0000000000007539.
• [2] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [3] MOG1: a new susceptibility gene for Brugada syndrome.Circ Cardiovasc Genet. 2011 Jun;4(3):261-8. doi: 10.1161/CIRCGENETICS.110.959130. Epub 2011 Mar 29.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.