Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE0EI8Z)

DOT Name Transcription factor RFX3 (RFX3)
Synonyms Regulatory factor X 3
Gene Name RFX3
Related Disease
Cerebellar ataxia ( )
Ciliopathy ( )
Ependymoma ( )
Sensorineural hearing loss disorder ( )
Skin disease ( )
Sleep disorder, initiating and maintaining sleep ( )
Autism spectrum disorder ( )
Complex neurodevelopmental disorder ( )
Corpus callosum, agenesis of ( )
UniProt ID
RFX3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF04589 ; PF02257
Sequence
MQTSETGSDTGSTVTLQTSVASQAAVPTQVVQQVPVQQQVQQVQTVQQVQHVYPAQVQYV
EGSDTVYTNGAIRTTTYPYTETQMYSQNTGGNYFDTQGSSAQVTTVVSSHSMVGTGGIQM
GVTGGQLISSSGGTYLIGNSMENSGHSVTHTTRASPATIEMAIETLQKSDGLSTHRSSLL
NSHLQWLLDNYETAEGVSLPRSTLYNHYLRHCQEHKLDPVNAASFGKLIRSIFMGLRTRR
LGTRGNSKYHYYGIRVKPDSPLNRLQEDMQYMAMRQQPMQQKQRYKPMQKVDGVADGFTG
SGQQTGTSVEQTVIAQSQHHQQFLDASRALPEFGEVEISSLPDGTTFEDIKSLQSLYREH
CEAILDVVVNLQFSLIEKLWQTFWRYSPSTPTDGTTITESSNLSEIESRLPKAKLITLCK
HESILKWMCNCDHGMYQALVEILIPDVLRPIPSALTQAIRNFAKSLEGWLSNAMNNIPQR
MIQTKVAAVSAFAQTLRRYTSLNHLAQAARAVLQNTSQINQMLSDLNRVDFANVQEQASW
VCQCDDNMVQRLETDFKMTLQQQSTLEQWAAWLDNVMMQALKPYEGRPSFPKAARQFLLK
WSFYSSMVIRDLTLRSAASFGSFHLIRLLYDEYMFYLVEHRVAQATGETPIAVMGEFGDL
NAVSPGNLDKDEGSEVESEMDEELDDSSEPQAKREKTELSQAFPVGCMQPVLETGVQPSL
LNPIHSEHIVTSTQTIRQCSATGNTYTAV
Function
Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development. Essential for the differentiation of nodal monocilia and left-right asymmetry specification during embryogenesis. Required for the biogenesis of motile cilia by governing growth and beating efficiency of motile cells. Also required for ciliated ependymal cell differentiation. Regulates the expression of genes involved in ciliary assembly (DYNC2LI1, FOXJ1 and BBS4) and genes involved in ciliary motility (DNAH11, DNAH9 and DNAH5). Together with RFX6, participates in the differentiation of 4 of the 5 islet cell types during endocrine pancreas development, with the exception of pancreatic PP (polypeptide-producing) cells. Regulates transcription by forming a heterodimer with another RFX protein and binding to the X-box in the promoter of target genes. Represses transcription of MAP1A in non-neuronal cells but not in neuronal cells.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cerebellar ataxia DIS9IRAV Strong Genetic Variation [1]
Ciliopathy DIS10G4I Strong Biomarker [2]
Ependymoma DISUMRNZ Strong Altered Expression [3]
Sensorineural hearing loss disorder DISJV45Z Strong Genetic Variation [1]
Skin disease DISDW8R6 Strong Biomarker [4]
Sleep disorder, initiating and maintaining sleep DISVOIRA Disputed Genetic Variation [5]
Autism spectrum disorder DISXK8NV Limited Autosomal dominant [6]
Complex neurodevelopmental disorder DISB9AFI Limited Autosomal dominant [6]
Corpus callosum, agenesis of DISO9P40 Limited Biomarker [7]
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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
4 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 Transcription factor RFX3 (RFX3). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Transcription factor RFX3 (RFX3). [15]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Transcription factor RFX3 (RFX3). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Transcription factor RFX3 (RFX3). [19]
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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 Transcription factor RFX3 (RFX3). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Transcription factor RFX3 (RFX3). [10]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Transcription factor RFX3 (RFX3). [11]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Transcription factor RFX3 (RFX3). [4]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Transcription factor RFX3 (RFX3). [13]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Transcription factor RFX3 (RFX3). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Transcription factor RFX3 (RFX3). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Transcription factor RFX3 (RFX3). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Transcription factor RFX3 (RFX3). [20]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Transcription factor RFX3 (RFX3). [21]
ORG2058 DMH1M6N Investigative ORG2058 increases the expression of Transcription factor RFX3 (RFX3). [22]
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⏷ Show the Full List of 11 Drug(s)

References

1 ATOH1/RFX1/RFX3 transcription factors facilitate the differentiation and characterisation of inner ear hair cell-like cells from patient-specific induced pluripotent stem cells harbouring A8344G mutation of mitochondrial DNA.Cell Death Dis. 2018 Apr 1;9(4):437. doi: 10.1038/s41419-018-0488-y.
2 RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies.J Cell Sci. 2009 Sep 1;122(Pt 17):3180-9. doi: 10.1242/jcs.048348. Epub 2009 Aug 11.
3 Microarray analysis reveals differential gene expression patterns in tumors of the pineal region.J Neuropathol Exp Neurol. 2006 Jul;65(7):675-84. doi: 10.1097/01.jnen.0000225907.90052.e3.
4 Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
5 Genome-wide analysis of insomnia disorder.Mol Psychiatry. 2018 Nov;23(11):2238-2250. doi: 10.1038/s41380-018-0033-5. Epub 2018 Mar 8.
6 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.
7 The role of primary cilia in corpus callosum formation is mediated by production of the Gli3 repressor.Hum Mol Genet. 2015 Sep 1;24(17):4997-5014. doi: 10.1093/hmg/ddv221. Epub 2015 Jun 12.
8 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.
9 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.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
12 Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
15 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
16 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.
17 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.
18 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.
19 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.
20 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.
21 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
22 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.