Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0EBW2J)

• DOT Name: Probable RNA-binding protein 46 (RBM46)
• Synonyms: Cancer/testis antigen 68; CT68; RNA-binding motif protein 46
• Gene Name: RBM46
• Related Disease: Neoplasm
• UniProt ID: RBM46_HUMAN
• Pfam ID: PF14709 ; PF00076
• Sequence:
  MNEENIDGTNGCSKVRTGIQNEAALLALMEKTGYNMVQENGQRKFGGPPPGWEGPPPPRG
  CEVFVGKIPRDMYEDELVPVFERAGKIYEFRLMMEFSGENRGYAFVMYTTKEEAQLAIRI
  LNNYEIRPGKFIGVCVSLDNCRLFIGAIPKEKKKEEILDEMKKVTEGVVDVIVYPSATDK
  TKNRGFAFVEYESHRAAAMARRKLIPGTFQLWGHTIQVDWADPEKEVDEETMQRVKVLYV
  RNLMISTTEETIKAEFNKFKPGAVERVKKLRDYAFVHFFNREDAVAAMSVMNGKCIDGAS
  IEVTLAKPVNKENTWRQHLNGQISPNSENLIVFANKEESHPKTLGKLPTLPARLNGQHSP
  SPPEVERCTYPFYPGTKLTPISMYSLKSNHFNSAVMHLDYYCNKNNWAPPEYYLYSTTSQ
  DGKVLLVYKIVIPAIANGSQSYFMPDKLCTTLEDAKELAAQFTLLHLDYNFHRSSINSLS
  PVSATLSSGTPSVLPYTSRPYSYPGYPLSPTISLANGSHVGQRLCISNQASFF
• Function: Essential for male and female fertility, playing a crucial role in regulating germ cell development by ensuring the proper progression of meiosis prophase I. Regulates mitotic-to-meiotic transition in spermatogenesis by forming a complex with MEIOC and YTHDC2 which recognizes and down-regulates mitotic transcripts for a successful meiotic entry. Required for normal synaptonemal complex formation during meiosis, binding meiotic cohesin subunit mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions and positively regulating their translation. Required for spermatogonial differentiation in both developing and adult testis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

2 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 Probable RNA-binding protein 46 (RBM46).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable RNA-binding protein 46 (RBM46).	[3]

References

• [1] Expression analysis of a panel of cancer-testis antigens in bladder cancer.Per Med. 2018 Nov;15(6):511-520. doi: 10.2217/pme-2018-0049. Epub 2018 Oct 26.
• [2] 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.
• [3] 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.