Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT29SSBE)

• DOT Name: Cerebellin-2 (CBLN2)
• Gene Name: CBLN2
• Related Disease:
  Autism spectrum disorder
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Pervasive developmental disorder
  Tourette syndrome
  High blood pressure
  Pulmonary hypertension
  Anxiety
  Anxiety disorder
• UniProt ID: CBLN2_HUMAN
• Pfam ID: PF00386
• Sequence:
  MQAPGRGPLGLRLMMPGRRGALREPGGCGSCLGVALALLLLLLPACCPVRAQNDTEPIVL
  EGKCLVVCDSSPSADGAVTSSLGISVRSGSAKVAFSATRSTNHEPSEMSNRTMTIYFDQV
  LVNIGNHFDLASSIFVAPRKGIYSFSFHVVKVYNRQTIQVSLMQNGYPVISAFAGDQDVT
  REAASNGVLLLMEREDKVHLKLERGNLMGGWKYSTFSGFLVFPL
• Function: Acts as a synaptic organizer in specific subsets of neurons in the brain. Essential for long-term maintenance but not establishment of excitatory synapses.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[2]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[2]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[1]
Tourette syndrome	DISX9D54	Strong	Biomarker	[1]
High blood pressure	DISY2OHH	moderate	Biomarker	[3]
Pulmonary hypertension	DIS1RSP5	Disputed	Biomarker	[4]
Anxiety	DISIJDBA	Limited	Biomarker	[5]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[5]

9 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 Cerebellin-2 (CBLN2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cerebellin-2 (CBLN2).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cerebellin-2 (CBLN2).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cerebellin-2 (CBLN2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cerebellin-2 (CBLN2).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cerebellin-2 (CBLN2).	[10]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Cerebellin-2 (CBLN2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cerebellin-2 (CBLN2).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cerebellin-2 (CBLN2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cerebellin-2 (CBLN2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cerebellin-2 (CBLN2).	[15]

References

• [1] Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism.Transl Psychiatry. 2012 Sep 4;2(9):e158. doi: 10.1038/tp.2012.75.
• [2] Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas.Oncotarget. 2017 Oct 9;8(58):98623-98634. doi: 10.18632/oncotarget.21697. eCollection 2017 Nov 17.
• [3] High Frequency of Pulmonary Hypertension-Causing Gene Mutation in Chinese Patients with Chronic Thromboembolic Pulmonary Hypertension.PLoS One. 2016 Jan 28;11(1):e0147396. doi: 10.1371/journal.pone.0147396. eCollection 2016.
• [4] Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension. Nat Genet. 2013 May;45(5):518-21. doi: 10.1038/ng.2581. Epub 2013 Mar 17.
• [5] 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.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] 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.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] 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.