Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5PB986)

DOT Name Rotatin (RTTN)
Gene Name RTTN
Related Disease
Microcephalic primordial dwarfism due to RTTN deficiency ( )
Brachydactyly ( )
Isolated congenital microcephaly ( )
Isolated growth hormone deficiency type IA ( )
Keloid ( )
Neoplasm ( )
Seckel syndrome ( )
Bilateral generalized polymicrogyria ( )
Asthma ( )
Intellectual disability ( )
UniProt ID
RTTN_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF14726
Sequence
MVLAGLIRKLGHQLAEIRERALKSILCKIEHNLICYADLIQERQLFLHLLEWFNFPSVPM
KEEVLNLLSRLVKYPPAVQHLVDVGAVEFLSKLRSNVEPNLQAEIDGILDGLFLLPSEVP
ALSSASYQTNQTELSKNPEILTGYFPQDKSNFQQMEVPPRPVVNQTVKCLKFSTFPWLPL
TTTDRHVLSSNESSLRSSNHTLIWNTCELLKDVIMQDFPAEIFLQRPKIVQSLLSLLKLA
FGDGKHRLALQSVSCLQQLCMYLRNRLNFHRDPGFFSNKHDTVSQNSSLSYCHEARGTHH
SQNPSPGSSSPRPSVVGRTGQRPRGDGQDWDAASSSGSSSHAHVNSRISVHSPLDMGHID
LPELETEDTLELQFQQLSLPQFCVSILESAVPLLRTGSRQVIIRVLELLTEDMTLIGEAI
STDIWDDSSLFGIDMKEKLLLVLGALGETMCYHKSSISLEQPEVMLVHHRMAFISISLFA
VRLLQTLLPVEKASEFLSEPMSTALFLLSLDMPISLEYPNIHEAVVAYLEQLNSENYSIY
KRTAEAVYSIECTCNFLSDIGKEGEKNLLELVELADQALRSFSYHQHFPLIKEIISICSK
IWKSAQASPLLQGESQKVLLHMLSHPLPRVKAETYHCCLEITKECLGVHNVTKPVSSLCN
GIHFLLHPKVLYEISVFGIQEPESEVNTAAKAILLYLLQGRLMMTALTWNKFIESLCPVI
PILQGYADTEDPLGNCILLLSKASSDTEEMLPCTTRLKSMLRLLLVKKPSVRSLALKLLA
FHLTSEEGADTKRPLIDARVLSRVTDLFIGKKPIELRLDDRRELVIKLETVEKVYEIFTS
DDVDLVLRKSAAEQLAVIMQDIKMHAVVKKLCLIDKIIEYLNECVSQDGKVVECLVQPCL
TLLRKVLCGDPVMRVSLSQQSSLLTVLFRVSLIFHEDCSVVTEVGALFCLLLFDEVSRMD
MWSVNPSNKPSLPSVFSLPVSVFRRYHLPVHVIGHHAVSPYSIVLPLSADCLALKPVSDM
LRIAWNLSWYHGSDNLLKQMNSETKTQEILDALKLSTEDILTLKITHMASGLQDCLHSIV
QAATHREVRAAVTRMSFYLLNDRLSLKGCPGPCGVTLKSLAWHTALNRFLQVLPACTEDE
KLLIDIIHFLNKLIKEQRKNSSLELLNWILELLLRHSANPLLDLLVLTESQAREETDDIR
TAVRQQLQKELIALFDTLLLNFMEVTDRKCSELLYVFQTQLALKLLQCLKVTDAPHFYGL
PSLERTLRGMANLTAFPGWSSHSPLTKPLDICVKYLSGLLEVITSFYVERGGNAMSFMGK
GVTKSTILCLLHLSHEMMAQAGSLEWMSLWFLPLGSHSEEHIPTQQGLAWLIPLWVDRDP
EVRFTSLGLGSALTTLETGCVALANSCQNISGGLWGTVVNILLDQSECSMVRREAAFILQ
NLLVIPMPTEIIKDYTWQGPCVHDEDSGLSLIGKPALQALLYHCHFYEHLNQMVKHCYLG
RCMFDLNFSAFDRNSESNDLNGLDDSFKFWRAPSRTSQDRDPSSLSTSETTVAPSLGSTE
FQPLVQSTTLLPEASHDQFVAQGHQESTSPRPPHDSSLSAPLPKLCVFVTPSLLSAMCSL
LDNLLTIAPRDTAKAFRQAHLIELLCSIADATLIQTCVQELRALLPSSPPAEHTQAQVSF
LLEYLSSLSRLLQSCLLVEPDLVIQDELVKPLITNIIGILTICTKDVLDKELISAFYHTW
THLFNLLAMLLRKAGAITLPFVTVALAKHWTAAIDMFCTCAGLSATCPALYTASLQFLSV
LLTEEAKGHLQAKSKTHLCCSPTVASLLDDSQENQKSLEQLSDVILQCYEGKSSKDILKR
VAANALMSLLAVSRRAQKHALKANLIDNCMEQMKHINAQLNLDSLRPGKAALKKKEDGVI
KELSIAMQLLRNCLYQNEECKEAALEAHLVPVLHSLWPWILMDDSLMQISLQLLCVYTAN
FPNGCSSLCWSSCGQHPVQATHRGAVSNSLMLCILKLASQMPLENTTVQQMVFMLLSNLA
LSHDCKGVIQKSNFLQNFLSLALPKGGNKHLSNLTILWLKLLLNISSGEDGQQMILRLDG
CLDLLTEMSKYKHKSSPLLPLLIFHNVCFSPANKPKILANEKVITVLAACLESENQNAQR
IGAAALWALIYNYQKAKTALKSPSVKRRVDEAYSLAKKTFPNSEANPLNAYYLKCLENLV
QLLNSS
Function
Involved in the genetic cascade that governs left-right specification. Plays a role in the maintenance of a normal ciliary structure. Required for correct asymmetric expression of NODAL, LEFTY and PITX2.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Microcephalic primordial dwarfism due to RTTN deficiency DIS25LK9 Definitive Autosomal recessive [1]
Brachydactyly DIS2533F Strong Genetic Variation [2]
Isolated congenital microcephaly DISUXHZ6 Strong Genetic Variation [3]
Isolated growth hormone deficiency type IA DISLPIAM Strong Genetic Variation [4]
Keloid DISV09JY Strong Genetic Variation [5]
Neoplasm DISZKGEW Strong Genetic Variation [5]
Seckel syndrome DISEVUBA Strong Genetic Variation [6]
Bilateral generalized polymicrogyria DISI2HKZ Moderate Autosomal recessive [7]
Asthma DISW9QNS Limited Genetic Variation [8]
Intellectual disability DISMBNXP Limited Biomarker [9]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Rotatin (RTTN). [10]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Rotatin (RTTN). [11]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Rotatin (RTTN). [12]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Rotatin (RTTN). [13]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Rotatin (RTTN). [14]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Rotatin (RTTN). [15]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Rotatin (RTTN). [16]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Rotatin (RTTN). [17]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Rotatin (RTTN). [18]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Rotatin (RTTN). [17]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Rotatin (RTTN). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Rotatin (RTTN). [20]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Rotatin (RTTN). [22]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Rotatin (RTTN). [24]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Rotatin (RTTN). [25]
chloropicrin DMSGBQA Investigative chloropicrin affects the expression of Rotatin (RTTN). [26]
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⏷ Show the Full List of 16 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Rotatin (RTTN). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Rotatin (RTTN). [23]
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References

1 RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans. Am J Hum Genet. 2015 Dec 3;97(6):862-8. doi: 10.1016/j.ajhg.2015.10.012. Epub 2015 Nov 19.
2 Primary microcephaly, primordial dwarfism, and brachydactyly in adult cases with biallelic skipping of RTTN exon 42.Hum Mutat. 2019 Jul;40(7):899-903. doi: 10.1002/humu.23755. Epub 2019 May 24.
3 Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction.Eur J Med Genet. 2018 Dec;61(12):755-758. doi: 10.1016/j.ejmg.2018.08.001. Epub 2018 Aug 16.
4 A neuropathological study of novel RTTN gene mutations causing a familial microcephaly with simplified gyral pattern.Birth Defects Res. 2018 Apr 17;110(7):598-602. doi: 10.1002/bdr2.1204. Epub 2018 Jan 22.
5 Differential susceptible loci expression in keloid and hypertrophic scars in the Chinese Han population.Ann Plast Surg. 2015 Jan;74(1):26-9. doi: 10.1097/SAP.0000000000000364.
6 Expanding the phenotype of RTTN variations: a new family with primary microcephaly, severe growth failure, brain malformations and dermatitis.Clin Genet. 2016 Nov;90(5):445-450. doi: 10.1111/cge.12771. Epub 2016 Apr 29.
7 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.
8 Sequence variant analysis of RNA sequences in severe equine asthma.PeerJ. 2018 Oct 11;6:e5759. doi: 10.7717/peerj.5759. eCollection 2018.
9 RTTN mutations link primary cilia function to organization of the human cerebral cortex.Am J Hum Genet. 2012 Sep 7;91(3):533-40. doi: 10.1016/j.ajhg.2012.07.008. Epub 2012 Aug 30.
10 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
11 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
12 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
13 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
14 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.
15 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.
16 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
17 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
18 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
19 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.
20 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
21 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
22 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
23 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.
24 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.
25 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
26 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.