Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1HFHN2)

• DOT Name: Coiled-coil domain-containing protein 28B (CCDC28B)
• Gene Name: CCDC28B
• Related Disease:
  Bardet biedl syndrome
  Hydrocephalus
  Ciliopathy
  Bardet-Biedl syndrome 1
• UniProt ID: CC28B_HUMAN
• Pfam ID: PF13270
• Sequence:
  MDDKKKKRSPKPCLAQPAQAPGTLRRVPVPTSHSGSLALGLPHLPSPKQRAKFKRVGKEK
  CRPVLAGGGSGSAGTPLQHSFLTEVTDVYEMEGGLLNLLNDFHSGRLQAFGKECSFEQLE
  HVREMQEKLARLHFSLDVCGEEEDDEEEEDGVTEGLPEEQKKTMADRNLDQLLSNLEDLS
  NSIQKLHLAENAEPEEQSAA
• Function: Involved in ciliogenesis. Regulates cilia length through its interaction with MAPKAP1/SIN1 but independently of mTORC2 complex. Modulates mTORC2 complex assembly and function, possibly enhances AKT1 phosphorylation. Does not seem to modulate assembly and function of mTORC1 complex.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bardet biedl syndrome	DISTBNZW	Strong	Biomarker	[1]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[2]
Ciliopathy	DIS10G4I	Limited	Biomarker	[2]
Bardet-Biedl syndrome 1	DISRLPZE	No Known	Autosomal recessive	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Coiled-coil domain-containing protein 28B (CCDC28B) increases the response to substance of Arsenic trioxide.	[14]

9 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 Coiled-coil domain-containing protein 28B (CCDC28B).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Coiled-coil domain-containing protein 28B (CCDC28B).	[13]

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 decreases the methylation of Coiled-coil domain-containing protein 28B (CCDC28B).	[11]

References

• [1] Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B.Sci Rep. 2018 Feb 14;8(1):3019. doi: 10.1038/s41598-018-21329-6.
• [2] Characterization of CCDC28B reveals its role in ciliogenesis and provides insight to understand its modifier effect on Bardet-Biedl syndrome.Hum Genet. 2013 Jan;132(1):91-105. doi: 10.1007/s00439-012-1228-5. Epub 2012 Sep 27.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [14] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.