Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKFNW3A)

• DOT Name: DNA-binding protein RFX7 (RFX7)
• Synonyms: Regulatory factor X 7; Regulatory factor X domain-containing protein 2
• Gene Name: RFX7
• Related Disease:
  3-M syndrome
  B-cell neoplasm
  Familial prostate carcinoma
  Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities
  Non-insulin dependent diabetes
  Obesity
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Small lymphocytic lymphoma
• UniProt ID: RFX7_HUMAN
• PDB ID: 4QQI; 6MEW
• Pfam ID: PF18326 ; PF02257
• Sequence:
  MAEEQQQPPPQQPDAHQQLPPSAPNSGVALPALVPGLPGTEASALQHKIKNSICKTVQSK
  VDCILQEVEKFTDLEKLYLYLQLPSGLSNGEKSDQNAMSSSRAQQMHAFSWIRNTLEEHP
  ETSLPKQEVYDEYKSYCDNLGYHPLSAADFGKIMKNVFPNMKARRLGTRGKSKYCYSGLR
  KKAFVHMPTLPNLDFHKTGDGLEGAEPSGQLQNIDEEVISSACRLVCEWAQKVLSQPFDT
  VLELARFLVKSHYIGTKSMAALTVMAAAPAGMKGITQPSAFIPTAESNSFQPQVKTLPSP
  IDAKQQLQRKIQKKQQEQKLQSPLPGESAAKKSESATSNGVTNLPNGNPSILSPQPIGIV
  VAAVPSPIPVQRTRQLVTSPSPMSSSDGKVLPLNVQVVTQHMQSVKQAPKTPQNVPASPG
  GDRSARHRYPQILPKPANTSALTIRSPTTVLFTSSPIKTAVVPASHMSSLNVVKMTTISL
  TPSNSNTPLKHSASVSSATGTTEESRSVPQIKNGSVVSLQSPGSRSSSAGGTSAVEVKVE
  PETSSDEHPVQCQENSDEAKAPQTPSALLGQKSNTDGALQKPSNEGVIEIKATKVCDQRT
  KCKSRCNEMLPGTSTGNNQSTITLSVASQNLTFTSSSSPPNGDSINKDPKLCTKSPRKRL
  SSTLQETQVPPVKKPIVEQLSAATIEGQKQGSVKKDQKVPHSGKTEGSTAGAQIPSKVSV
  NVSSHIGANQPLNSSALVISDSALEQQTTPSSSPDIKVKLEGSVFLLDSDSKSVGSFNPN
  GWQQITKDSEFISASCEQQQDISVMTIPEHSDINDLEKSVWELEGMPQDTYSQQLHSQIQ
  ESSLNQIQAHSSDQLPLQSELKEFEPSVSQTNESYFPFDDELTQDSIVEELVLMEQQMSM
  NNSHSYGNCLGMTLQSQSVTPGAPMSSHTSSTHFYHPIHSNGTPIHTPTPTPTPTPTPTP
  TPTPTSEMIAGSQSLSRESPCSRLAQTTPVDSALGSSRHTPIGTPHSNCSSSVPPSPVEC
  RNPFAFTPISSSMAYHDASIVSSSPVKPMQRPMATHPDKTKLEWMNNGYSGVGNSSVSGH
  GILPSYQELVEDRFRKPHAFAVPGQSYQSQSRHHDTHFGRLTPVSPVQHQGATVNNTNKQ
  EGFAVPAPLDNKGTNSSASSNFRCRSVSPAVHRQRNLSGSTLYPVSNIPRSNVTPFGSPV
  TPEVHVFTNVHTDACANNIAQRSQSVPLTVMMQTAFPNALQKQANSKKITNVLLSKLDSD
  NDDAVRGLGMNNLPSNYTARMNLTQILEPSTVFPSANPQNMIDSSTSVYEFQTPSYLTKS
  NSTGQINFSPGDNQAQSEIGEQQLDFNSTVKDLLSGDSLQTNQQLVGQGASDLTNTASDF
  SSDIRLSSELSGSINDLNTLDPNLLFDPGRQQGQDDEATLEELKNDPLFQQICSESMNSM
  TSSGFEWIESKDHPTVEMLG
• Function: Transcription factor. Acts as a transcriptional activator by binding to promoter regions of target genes, such as PDCD4, PIK3IP1, MXD4, PNRC1, and RFX5. Plays a role in natural killer (NK) cell maintenance and immunity. May play a role in the process of ciliogenesis in the neural tube and neural tube closure.
• Tissue Specificity: Widely expressed in many different tissue types including thymus and placenta, with high expression in brain . Expressed in both inhibitory and excitatory neurons in cortex .

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
3-M syndrome	DISGKJY3	Strong	Biomarker	[1]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[2]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[3]
Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities	DISU6ABK	Strong	Autosomal dominant	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[3]
Small lymphocytic lymphoma	DIS30POX	Disputed	Genetic Variation	[6]

11 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 DNA-binding protein RFX7 (RFX7).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA-binding protein RFX7 (RFX7).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA-binding protein RFX7 (RFX7).	[9]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of DNA-binding protein RFX7 (RFX7).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA-binding protein RFX7 (RFX7).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of DNA-binding protein RFX7 (RFX7).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA-binding protein RFX7 (RFX7).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DNA-binding protein RFX7 (RFX7).	[15]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of DNA-binding protein RFX7 (RFX7).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DNA-binding protein RFX7 (RFX7).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA-binding protein RFX7 (RFX7).	[19]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of DNA-binding protein RFX7 (RFX7).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of DNA-binding protein RFX7 (RFX7).	[16]

References

• [1] Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome protein CCDC8.Structure. 2015 Apr 7;23(4):700-12. doi: 10.1016/j.str.2015.02.001. Epub 2015 Mar 5.
• [2] PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.Nat Commun. 2019 Mar 29;10(1):1415. doi: 10.1038/s41467-019-09180-3.
• [3] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [4] The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014 Nov 13;515(7526):216-21. doi: 10.1038/nature13908. Epub 2014 Oct 29.
• [5] Multiple genetic variations confer risks for obesity and type 2 diabetes mellitus in arab descendants from UAE.Int J Obes (Lond). 2018 Jul;42(7):1345-1353. doi: 10.1038/s41366-018-0057-6. Epub 2018 Mar 12.
• [6] A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.Nat Genet. 2014 Jan;46(1):56-60. doi: 10.1038/ng.2843. Epub 2013 Dec 1.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [11] 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.
• [12] 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.
• [13] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.