Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAKMUS2)

• DOT Name: Protein chibby homolog 1 (CBY1)
• Synonyms: ARPP-binding protein; Cytosolic leucine-rich protein; PIGEA-14; PKD2 interactor, Golgi and endoplasmic reticulum-associated 1
• Gene Name: CBY1
• Related Disease:
  Ependymoma
  Laryngeal carcinoma
  Laryngeal squamous cell carcinoma
  Otitis media
  Ciliopathy
  Joubert syndrome
  Colorectal carcinoma
  Neoplasm
• UniProt ID: CBY1_HUMAN
• PDB ID: 4WRQ
• Pfam ID: PF14645
• Sequence:
  MPFFGNTFSPKKTPPRKSASLSNLHSLDRSTREVELGLEYGSPTMNLAGQSLKFENGQWI
  AETGVSGGVDRREVQRLRRRNQQLEEENNLLRLKVDILLDMLSESTAESHLMEKELDELR
  ISRKRK
• Function: Inhibits the Wnt/Wingless pathway by binding to CTNNB1/beta-catenin and inhibiting beta-catenin-mediated transcriptional activation through competition with TCF/LEF transcription factors. Has also been shown to play a role in regulating the intracellular trafficking of polycystin-2/PKD2 and possibly of other intracellular proteins. Promotes adipocyte and cardiomyocyte differentiation.
• Tissue Specificity: Widely expressed. Expressed at higher levels in heart, skeletal muscle, kidney and placenta. Also found in brain, lung, liver and testis. Significantly down-regulated in thyroid and metastatic uterine tumors.
• KEGG Pathway: Wnt sig.ling pathway (hsa04310)
• Reactome Pathway: Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ependymoma	DISUMRNZ	Definitive	Altered Expression	[1]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[2]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Posttranslational Modification	[3]
Otitis media	DISGZDUO	Strong	Biomarker	[4]
Ciliopathy	DIS10G4I	Moderate	Autosomal recessive	[5]
Joubert syndrome	DIS7P5CO	Supportive	Autosomal recessive	[6]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[7]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein chibby homolog 1 (CBY1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein chibby homolog 1 (CBY1).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein chibby homolog 1 (CBY1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein chibby homolog 1 (CBY1).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein chibby homolog 1 (CBY1).	[12]

References

• [1] Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13.Genes Chromosomes Cancer. 2008 Nov;47(11):1005-22. doi: 10.1002/gcc.20607.
• [2] Downregulated Chibby in laryngeal squamous cell carcinoma with increased expression in laryngeal carcinoma Hep-2 cells.Oncol Rep. 2014 Nov;32(5):1947-56. doi: 10.3892/or.2014.3451. Epub 2014 Aug 29.
• [3] Expression of CBY and methylation of CBY at promoter region in human laryngeal squamous cell carcinoma.Tumori. 2015 Mar-Apr;101(2):215-22. doi: 10.5301/tj.5000242. Epub 2015 Mar 20.
• [4] Altered lung morphogenesis, epithelial cell differentiation and mechanics in mice deficient in the Wnt/-catenin antagonist Chibby.PLoS One. 2010 Oct 25;5(10):e13600. doi: 10.1371/journal.pone.0013600.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] Loss of CBY1 results in a ciliopathy characterized by features of Joubert syndrome. Hum Mutat. 2020 Dec;41(12):2179-2194. doi: 10.1002/humu.24127. Epub 2020 Nov 1.
• [7] Is the gene encoding Chibby implicated as a tumour suppressor in colorectal cancer ?.BMC Cancer. 2004 Jul 9;4:31. doi: 10.1186/1471-2407-4-31.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.