Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNJGQ11)

• DOT Name: Centrosomal protein of 83 kDa (CEP83)
• Synonyms: Cep83; Coiled-coil domain-containing protein 41; Renal carcinoma antigen NY-REN-58
• Gene Name: CEP83
• Related Disease:
  Congenital nervous system disorder
  Intellectual disability
  Nephronophthisis 18
  Nephronophthisis 2
• UniProt ID: CEP83_HUMAN
• Sequence:
  MVVSTFTDMDTFPNNFPPGGDSGLTGSQSEFQKMLIDERLRCEHHKANYQTLKAEHTRLQ
  NEHVKLQNELKHLFNEKQTQQEKLQLLLEELRGELVEKTKDLEEMKLQILTPQKLELLRA
  QIQQELETPMRERFRNLDEEVEKYRAVYNKLRYEHTFLKSEFEHQKEEYARILDEGKIKY
  ESEIARLEEDKEELRNQLLNVDLTKDSKRVEQLAREKVYLCQKLKGLEAEVAELKAEKEN
  SEAQVENAQRIQVRQLAEMQATVRSLEAEKQSANLRAERLEKELQSSSEQNTFLINKLHK
  AEREINTLSSKVKELKHSNKLEITDIKLETARAKSELERERNKIQSELDGLQSDNEILKA
  AVEHHKVLLVEKDRELIRKVQAAKEEGYQKLVVLQDEKLELENRLADLEKMKVEHDVWRQ
  SEKDQYEEKLRASQMAEEITRKELQSVRLKLQQQIVTIENAEKEKNENSDLKQQISSLQI
  QVTSLAQSENDLLNSNQMLKEMVERLKQECRNFRSQAEKAQLEAEKTLEEKQIQWLEEKH
  KLHERITDREEKYNQAKEKLQRAAIAQKKRKSLHENKLKRLQEKVEVLEAKKEELETENQ
  VLNRQNVPFEDYTRLQKRLKDIQRRHNEFRSLILVPNMPPTASINPVSFQSSAMVPSMEL
  PFPPHMQEEQHQRELSLLRKRLEELETTQRKQLEELGSSGE
• Function: Component of the distal appendage region of the centriole involved in the initiation of primary cilium assembly. May collaborate with IFT20 in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium during the initiation of primary cilium assembly.
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital nervous system disorder	DIS2BIP8	Strong	Genetic Variation	[1]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[1]
Nephronophthisis 18	DISN8HRE	Strong	Autosomal recessive	[2]
Nephronophthisis 2	DIS5Y5KV	Supportive	Autosomal recessive	[1]

2 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 Centrosomal protein of 83 kDa (CEP83).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Centrosomal protein of 83 kDa (CEP83).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centrosomal protein of 83 kDa (CEP83).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centrosomal protein of 83 kDa (CEP83).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Centrosomal protein of 83 kDa (CEP83).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Centrosomal protein of 83 kDa (CEP83).	[7]
ORG2058	DMH1M6N	Investigative	ORG2058 decreases the expression of Centrosomal protein of 83 kDa (CEP83).	[9]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Centrosomal protein of 83 kDa (CEP83).	[10]

References

• [1] Mutations of CEP83 cause infantile nephronophthisis and intellectual disability. Am J Hum Genet. 2014 Jun 5;94(6):905-14. doi: 10.1016/j.ajhg.2014.05.002. Epub 2014 May 29.
• [2] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] 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.
• [9] The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.
• [10] Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.