Details of Drug Off-Target (DOT)

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

• DOT Name: Ribonucleoprotein PTB-binding 1 (RAVER1)
• Synonyms: Protein raver-1
• Gene Name: RAVER1
• Related Disease:
  Familial hypercholesterolemia
  Rheumatoid arthritis
  Ankylosing spondylitis
  Crohn disease
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: RAVR1_HUMAN
• PDB ID: 3H2U; 3H2V; 3SMZ; 3VF0
• Pfam ID: PF00076
• Sequence:
  MAADVSVTHRPPLSPKSGAEVEAGDAAERRAPEEELPPLDPEEIRKRLEHTERQFRNRRK
  ILIRGLPGDVTNQEVHDLLSDYELKYCFVDKYKGTAFVTLLNGEQAEAAINAFHQSRLRE
  RELSVQLQPTDALLCVANLPPSLTQQQFEELVRPFGSLERCFLVYSERTGQSKGYGFAEY
  MKKDSAARAKSDLLGKPLGPRTLYVHWTDAGQLTPALLHSRCLCVDRLPPGFNDVDALCR
  ALSAVHSPTFCQLACGQDGQLKGFAVLEYETAEMAEEAQQQADGLSLGGSHLRVSFCAPG
  PPGRSMLAALIAAQATALNRGKGLLPEPNILQLLNNLGPSASLQLLLNPLLHGSAGGKQG
  LLGAPPAMPLLNGPALSTALLQLALQTQGQKKPGILGDSPLGALQPGAQPANPLLGELPA
  GGGLPPELPPRRGKPPPLLPSVLGPAGGDREALGLGPPAAQLTPPPAPVGLRGSGLRGPL
  SHFYSGSPTSYFTSGLQAGLKQSHLSKAIGSSPLGSGEGLLGLSPGPNGHSHLLKVRAGG
  GDMQGWEAPAPQRPLTRPALPSVSRPHWAARNAALPTCCPRPSPAQKAAMWASTPRASAA
  TTRTPT
• Function: Cooperates with PTBP1 to modulate regulated alternative splicing events. Promotes exon skipping. Cooperates with PTBP1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial hypercholesterolemia	DISC06IX	Strong	Genetic Variation	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[3]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[3]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[3]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[3]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[3]

1 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 Ribonucleoprotein PTB-binding 1 (RAVER1).	[4]

4 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 Ribonucleoprotein PTB-binding 1 (RAVER1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribonucleoprotein PTB-binding 1 (RAVER1).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Ribonucleoprotein PTB-binding 1 (RAVER1).	[7]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Ribonucleoprotein PTB-binding 1 (RAVER1).	[8]

References

• [1] Low-density lipoprotein receptor mutations generate synthetic genome-wide associations.Eur J Hum Genet. 2013 May;21(5):563-6. doi: 10.1038/ejhg.2012.207. Epub 2012 Sep 12.
• [2] High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.Nat Genet. 2012 Dec;44(12):1336-40. doi: 10.1038/ng.2462. Epub 2012 Nov 11.
• [3] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [8] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.