Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP5X5WA)

DOT Name WD repeat-containing protein 19
Synonyms Intraflagellar transport 144 homolog
Gene Name WDR19
Related Disease
Asphyxiating thoracic dystrophy 5 ( )
Ciliopathy ( )
Cranioectodermal dysplasia 4 ( )
Nephronophthisis 13 ( )
Senior-Loken syndrome 8 ( )
Cranioectodermal dysplasia ( )
Jeune syndrome ( )
Nephronophthisis 1 ( )
Senior-Loken syndrome ( )
UniProt ID
WDR19_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8BBF; 8BBG; 8FGW; 8FH3
Pfam ID
PF00400 ; PF15911
Sequence
MKRIFSLLEKTWLGAPIQFAWQKTSGNYLAVTGADYIVKIFDRHGQKRSEINLPGNCVAM
DWDKDGDVLAVIAEKSSCIYLWDANTNKTSQLDNGMRDQMSFLLWSKVGSFLAVGTVKGN
LLIYNHQTSRKIPVLGKHTKRITCGCWNAENLLALGGEDKMITVSNQEGDTIRQTQVRSE
PSNMQFFLMKMDDRTSAAESMISVVLGKKTLFFLNLNEPDNPADLEFQQDFGNIVCYNWY
GDGRIMIGFSCGHFVVISTHTGELGQEIFQARNHKDNLTSIAVSQTLNKVATCGDNCIKI
QDLVDLKDMYVILNLDEENKGLGTLSWTDDGQLLALSTQRGSLHVFLTKLPILGDACSTR
IAYLTSLLEVTVANPVEGELPITVSVDVEPNFVAVGLYHLAVGMNNRAWFYVLGENAVKK
LKDMEYLGTVASICLHSDYAAALFEGKVQLHLIESEILDAQEERETRLFPAVDDKCRILC
HALTSDFLIYGTDTGVVQYFYIEDWQFVNDYRHPVSVKKIFPDPNGTRLVFIDEKSDGFV
YCPVNDATYEIPDFSPTIKGVLWENWPMDKGVFIAYDDDKVYTYVFHKDTIQGAKVILAG
STKVPFAHKPLLLYNGELTCQTQSGKVNNIYLSTHGFLSNLKDTGPDELRPMLAQNLMLK
RFSDAWEMCRILNDEAAWNELARACLHHMEVEFAIRVYRRIGNVGIVMSLEQIKGIEDYN
LLAGHLAMFTNDYNLAQDLYLASSCPIAALEMRRDLQHWDSALQLAKHLAPDQIPFISKE
YAIQLEFAGDYVNALAHYEKGITGDNKEHDEACLAGVAQMSIRMGDIRRGVNQALKHPSR
VLKRDCGAILENMKQFSEAAQLYEKGLYYDKAASVYIRSKNWAKVGDLLPHVSSPKIHLQ
YAKAKEADGRYKEAVVAYENAKQWQSVIRIYLDHLNNPEKAVNIVRETQSLDGAKMVARF
FLQLGDYGSAIQFLVMSKCNNEAFTLAQQHNKMEIYADIIGSEDTTNEDYQSIALYFEGE
KRYLQAGKFFLLCGQYSRALKHFLKCPSSEDNVAIEMAIETVGQAKDELLTNQLIDHLLG
ENDGMPKDAKYLFRLYMALKQYREAAQTAIIIAREEQSAGNYRNAHDVLFSMYAELKSQK
IKIPSEMATNLMILHSYILVKIHVKNGDHMKGARMLIRVANNISKFPSHIVPILTSTVIE
CHRAGLKNSAFSFAAMLMRPEYRSKIDAKYKKKIEGMVRRPDISEIEEATTPCPFCKFLL
PECELLCPGCKNSIPYCIATGRHMLKDDWTVCPHCDFPALYSELKIMLNTESTCPMCSER
LNAAQLKKISDCTQYLRTEEEL
Function
As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly. Essential for functional IFT-A assembly and ciliary entry of GPCRs. Associates with the BBSome complex to mediate ciliary transport.
Tissue Specificity
Some isoforms are tissue-specific. Highly expressed in the prostate. Lower expression in the cerebellum, pituitary gland, fetal lung, and pancreas. In normal prostate, expressed in both basal and luminal epithelial cells. No expression detected in fibromuscular stromal cells, endothelial cells, or infiltrating lymphocytes. Uniformed expression in prostate adenocarcinoma cells.
Reactome Pathway
Intraflagellar transport (R-HSA-5620924 )
Hedgehog 'off' state (R-HSA-5610787 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Asphyxiating thoracic dystrophy 5 DISCKBCE Definitive Autosomal recessive [1]
Ciliopathy DIS10G4I Definitive Autosomal recessive [2]
Cranioectodermal dysplasia 4 DISQDMZW Definitive Autosomal recessive [3]
Nephronophthisis 13 DIS9M0EA Strong Autosomal recessive [3]
Senior-Loken syndrome 8 DISP8HRY Strong Autosomal recessive [3]
Cranioectodermal dysplasia DISW7Y64 Supportive Autosomal recessive [4]
Jeune syndrome DISLC357 Supportive Autosomal recessive [3]
Nephronophthisis 1 DIS7QNQ3 Supportive Autosomal recessive [3]
Senior-Loken syndrome DISGBSGP Supportive Autosomal recessive [5]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 WD repeat-containing protein 19. [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of WD repeat-containing protein 19. [11]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of WD repeat-containing protein 19. [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of WD repeat-containing protein 19. [8]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of WD repeat-containing protein 19. [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of WD repeat-containing protein 19. [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of WD repeat-containing protein 19. [12]
Selenium DM25CGV Approved Selenium decreases the expression of WD repeat-containing protein 19. [13]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of WD repeat-containing protein 19. [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of WD repeat-containing protein 19. [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of WD repeat-containing protein 19. [15]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of WD repeat-containing protein 19. [16]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of WD repeat-containing protein 19. [17]
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⏷ Show the Full List of 11 Drug(s)

References

1 Jeune syndrome: description of 13 cases and a proposal for follow-up protocol. Eur J Pediatr. 2010 Jan;169(1):77-88. doi: 10.1007/s00431-009-0991-3. Epub 2009 May 10.
2 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
3 Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19. Am J Hum Genet. 2011 Nov 11;89(5):634-43. doi: 10.1016/j.ajhg.2011.10.001. Epub 2011 Oct 20.
4 Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):165-74. doi: 10.1002/ajmg.c.31336. Epub 2012 Jul 12.
5 WDR19: an ancient, retrograde, intraflagellar ciliary protein is mutated in autosomal recessive retinitis pigmentosa and in Senior-Loken syndrome. Clin Genet. 2013 Aug;84(2):150-9. doi: 10.1111/cge.12196.
6 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.
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 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.
9 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
10 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.
11 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
12 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
13 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.
14 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
15 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
16 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.
17 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.