Details of Drug Off-Target (DOT)

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

• DOT Name: RNA guanine-N7 methyltransferase activating subunit (RAMAC)
• Synonyms: Protein FAM103A1; RNA guanine-7 methyltransferase activating subunit; RNMT-activating mRNA cap methyltransferase subunit; RNMT-activating mini protein; RAM
• Gene Name: RAMAC
• Related Disease:
  Neoplasm
  Acute myelogenous leukaemia
  Adult respiratory distress syndrome
  Congenital alveolar dysplasia
  Advanced cancer
• UniProt ID: RAMAC_HUMAN
• PDB ID: 5E8J
• Pfam ID: PF15320
• Sequence:
  MTDTAEAVPKFEEMFASRFTENDKEYQEYLKRPPESPPIVEEWNSRAGGNQRNRGNRLQD
  NRQFRGRDNRWGWPSDNRSNQWHGRSWGNNYPQHRQEPYYPQQYGHYGYNQRPPYGYY
• Function: Regulatory subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Promotes the recruitment of the methyl donor, S-adenosyl-L-methionine, to RNMT. Regulates RNMT expression by a post-transcriptional stabilizing mechanism. Binds RNA.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[3]
Congenital alveolar dysplasia	DIS1IYUN	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA guanine-N7 methyltransferase activating subunit (RAMAC).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RNA guanine-N7 methyltransferase activating subunit (RAMAC).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA guanine-N7 methyltransferase activating subunit (RAMAC).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of RNA guanine-N7 methyltransferase activating subunit (RAMAC).	[8]

References

• [1] Previous Immune Checkpoint Inhibitor Treatment to Increase the Efficacy of Docetaxel and Ramucirumab Combination Chemotherapy.Anticancer Res. 2019 Sep;39(9):4987-4993. doi: 10.21873/anticanres.13688.
• [2] Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia.Pediatr Transplant. 2018 Dec;22(8):e13291. doi: 10.1111/petr.13291. Epub 2018 Sep 15.
• [3] A randomized trial comparing the short binasal prong to the RAM cannula for noninvasive ventilation support of preterm infants with respiratory distress syndrome.J Matern Fetal Neonatal Med. 2021 Jun;34(12):1868-1874. doi: 10.1080/14767058.2019.1651268. Epub 2019 Aug 8.
• [4] Expression levels of ROS1/ALK/c-MET and therapeutic efficacy of cetuximab plus chemotherapy in advanced biliary tract cancer.Sci Rep. 2016 May 3;6:25369. doi: 10.1038/srep25369.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.