Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUTO9NZ)

• DOT Name: RNA-binding protein 48 (RBM48)
• Gene Name: RBM48
• Related Disease: Nephronophthisis
• UniProt ID: RBM48_HUMAN
• PDB ID: 7DVQ
• Sequence:
  MASSGGELGSLFDHHVQRAVCDTRAKYREGRRPRAVKVYTINLESQYLLIQGVPAVGVMK
  ELVERFALYGAIEQYNALDEYPAEDFTEVYLIKFMNLQSARTAKRKMDEQSFFGGLLHVC
  YAPEFETVEETRKKLQMRKAYVVKTTENKDHYVTKKKLVTEHKDTEDFRQDFHSEMSGFC
  KAALNTSAGNSNPYLPYSCELPLCYFSSKCMCSSGGPVDRAPDSSKDGRNHHKTMGHYNH
  NDSLRKTQINSLKNSVACPGAQKAITSSEAVDRFMPRTTQLQERKRRREDDRKLGTFLQT
  NPTGNEIMIGPLLPDISKVDMHDDSLNTTANLIRHKLKEVISSVPKPPEDKPEDVHTSHP
  LKQRRRI
• Function: As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephronophthisis	DISXU4HY	Strong	Genetic Variation	[1]

7 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 48 (RBM48).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of RNA-binding protein 48 (RBM48).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of RNA-binding protein 48 (RBM48).	[4]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of RNA-binding protein 48 (RBM48).	[5]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of RNA-binding protein 48 (RBM48).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of RNA-binding protein 48 (RBM48).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of RNA-binding protein 48 (RBM48).	[8]

References

• [1] Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.Kidney Int. 2016 Feb;89(2):468-475. doi: 10.1038/ki.2015.317.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.