Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO7QW6Y)

• DOT Name: Cerebellin-4 (CBLN4)
• Synonyms: Cerebellin-like glycoprotein 1
• Gene Name: CBLN4
• Related Disease:
  Alzheimer disease
  Cerebellar ataxia
  Varicose veins
  Anxiety
  Anxiety disorder
• UniProt ID: CBLN4_HUMAN
• Pfam ID: PF00386
• Sequence:
  MGSGRRALSAVPAVLLVLTLPGLPVWAQNDTEPIVLEGKCLVVCDSNPATDSKGSSSSPL
  GISVRAANSKVAFSAVRSTNHEPSEMSNKTRIIYFDQILVNVGNFFTLESVFVAPRKGIY
  SFSFHVIKVYQSQTIQVNLMLNGKPVISAFAGDKDVTREAATNGVLLYLDKEDKVYLKLE
  KGNLVGGWQYSTFSGFLVFPL
• Function: Acts as a synaptic organizer in specific subsets of neurons in the brain. Essential for the formation and maintenance of inhibitory GABAergic synapses. Promotes the development of dendrite-targeting inhibitory GABAergic synapses made by somatostatin-positive interneurons. May contribute to the function of ventral medial habenula region of the brain implicated in the regulation of anxiety-related behaviors. May play a role in CBLN3 export from the endoplasmic reticulum and secretion.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[2]
Varicose veins	DISIMBN2	Strong	Biomarker	[1]
Anxiety	DISIJDBA	Limited	Genetic Variation	[3]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[3]

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 Cerebellin-4 (CBLN4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cerebellin-4 (CBLN4).	[5]

References

• [1] Cerebellin 4, a synaptic protein, enhances inhibitory activity and resistance of neurons to amyloid- toxicity.Neurobiol Aging. 2015 Feb;36(2):1057-71. doi: 10.1016/j.neurobiolaging.2014.11.006. Epub 2014 Nov 15.
• [2] Glycosylation of Cblns attenuates their receptor binding.Brain Res. 2018 Sep 1;1694:129-139. doi: 10.1016/j.brainres.2018.05.022. Epub 2018 May 18.
• [3] Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs.Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10235-E10244. doi: 10.1073/pnas.1811086115. Epub 2018 Oct 4.
• [4] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.