Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQH008A)

• DOT Name: Clavesin-1 (CLVS1)
• Synonyms: Cellular retinaldehyde-binding protein-like; Retinaldehyde-binding protein 1-like 1; clathrin vesicle-associated Sec14 protein 1
• Gene Name: CLVS1
• Related Disease:
  Hepatocellular carcinoma
  Migraine disorder
  Schizophrenia
  Central diabetes insipidus
  Amyotrophic lateral sclerosis type 1
• UniProt ID: CLVS1_HUMAN
• Pfam ID: PF00650 ; PF03765
• Sequence:
  MGPVSLLPKYQKLNTWNGDLAKMTHLQAGLSPETIEKARLELNENPDVLHQDIQQVRDMI
  ITRPDIGFLRTDDAFILRFLRARKFHQADAFRLLAQYFQYRQLNLDMFKNFKADDPGIKR
  ALIDGFPGVLENRDHYGRKILLLFAANWDQSRNSFTDILRAILLSLEVLIEDPELQINGF
  ILIIDWSNFSFKQASKLTPSILKLAIEGLQDSFPARFGGVHFVNQPWYIHALYTLIKPFL
  KDKTRKRIFLHGNNLNSLHQLIHPEFLPSEFGGTLPPYDMGTWARTLLGPDYSDENDYTH
  TSYNAMHVKHTSSNLERECSPKLMKRSQSVVEAGTLKHEEKGENENTQPLLALD
• Function: Required for normal morphology of late endosomes and/or lysosomes in neurons. Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
• Tissue Specificity: Expressed mainly in the brain.
• Reactome Pathway: Lysosome Vesicle Biogenesis (R-HSA-432720)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Central diabetes insipidus	DISJ4P9O	moderate	Genetic Variation	[4]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Limited	Genetic Variation	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Clavesin-1 (CLVS1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Clavesin-1 (CLVS1).	[7]

References

• [1] Cellular retinaldehyde-binding protein-like (CRALBPL), a novel human Sec14p-like gene that is upregulated in human hepatocellular carcinomas, may be used as a marker for human hepatocellular carcinomas.DNA Cell Biol. 2008 Mar;27(3):159-63. doi: 10.1089/dna.2007.0634.
• [2] Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
• [3] Genetic basis of psychopathological dimensions shared between schizophrenia and bipolar disorder.Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:23-29. doi: 10.1016/j.pnpbp.2018.08.023. Epub 2018 Aug 24.
• [4] Host genetic susceptibility to Clostridium difficile infections in patients undergoing autologous stem cell transplantation: a genome-wide association study.Support Care Cancer. 2018 Sep;26(9):3127-3134. doi: 10.1007/s00520-018-4173-6. Epub 2018 Mar 28.
• [5] Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.Neurobiol Aging. 2014 Jul;35(7):1778.e9-1778.e23. doi: 10.1016/j.neurobiolaging.2014.01.014. Epub 2014 Jan 17.
• [6] 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.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.