Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL2WXOR)

DOT Name Centrosomal protein of 19 kDa (CEP19)
Synonyms Cep19
Gene Name CEP19
Related Disease
Ciliopathy ( )
Obesity ( )
Obesity due to CEP19 deficiency ( )
Polydactyly ( )
Bardet biedl syndrome ( )
UniProt ID
CEP19_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF14933
Sequence
MMCTAKKCGIRFQPPAIILIYESEIKGKIRQRIMPVRNFSKFSDCTRAAEQLKNNPRHKS
YLEQVSLRQLEKLFSFLRGYLSGQSLAETMEQIQRETTIDPEEDLNKLDDKELAKRKSIM
DELFEKNQKKKDDPNFVYDIEVEFPQDDQLQSCGWDTESADEF
Function
Required for ciliation. Recruits the RABL2B GTPase to the ciliary base to initiate ciliation. After specifically capturing the activated GTP-bound RABL2B, the CEP19-RABL2B complex binds intraflagellar transport (IFT) complex B from the large pool pre-docked at the base of the cilium and thus triggers its entry into the cilia. Involved in the early steps in cilia formation by recruiting the ciliary vesicles (CVs) to the distal end of the mother centriole where they fuse to initiate cilium assembly. Involved in microtubule (MT) anchoring to the centrosomes.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ciliopathy DIS10G4I Strong Genetic Variation [1]
Obesity DIS47Y1K Strong Genetic Variation [2]
Obesity due to CEP19 deficiency DISLZ3VA Strong Autosomal recessive [3]
Polydactyly DIS25BMZ Strong CausalMutation [4]
Bardet biedl syndrome DISTBNZW Supportive Autosomal recessive [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 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 Centrosomal protein of 19 kDa (CEP19). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Centrosomal protein of 19 kDa (CEP19). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Centrosomal protein of 19 kDa (CEP19). [7]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Centrosomal protein of 19 kDa (CEP19). [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Centrosomal protein of 19 kDa (CEP19). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Centrosomal protein of 19 kDa (CEP19). [10]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Centrosomal protein of 19 kDa (CEP19). [11]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Centrosomal protein of 19 kDa (CEP19). [12]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Centrosomal protein of 19 kDa (CEP19). [13]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Centrosomal protein of 19 kDa (CEP19). [14]
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⏷ Show the Full List of 10 Drug(s)

References

1 CEP19 cooperates with FOP and CEP350 to drive early steps in the ciliogenesis programme.Open Biol. 2017 Jun;7(6):170114. doi: 10.1098/rsob.170114.
2 Gating Ciliary Transport.Dev Cell. 2017 Jul 10;42(1):5-6. doi: 10.1016/j.devcel.2017.06.016.
3 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.
4 Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. J Med Genet. 2018 Mar;55(3):189-197. doi: 10.1136/jmedgenet-2017-104758. Epub 2017 Nov 10.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 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.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
9 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
10 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
11 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
12 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.
13 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
14 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.