Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDX1026)

• DOT Name: DNA-binding protein RFXANK (RFXANK)
• Synonyms: Ankyrin repeat family A protein 1; Regulatory factor X subunit B; RFX-B; Regulatory factor X-associated ankyrin-containing protein
• Gene Name: RFXANK
• Related Disease:
  MHC class II deficiency
  Adenocarcinoma
  Advanced cancer
  B-cell lymphoma
  Colorectal neoplasm
  Large cell lymphoma
  Neoplasm
  Chronic renal failure
  End-stage renal disease
  Bladder transitional cell carcinoma
• UniProt ID: RFXK_HUMAN
• PDB ID: 3UXG; 3V30; 6MEW
• Pfam ID: PF12796
• Sequence:
  MELTQPAEDLIQTQQTPASELGDPEDPGEEAADGSDTVVLSLFPCTPEPVNPEPDASVSS
  PQAGSSLKHSTTLTNRQRGNEVSALPATLDSLSIHQLAAQGELDQLKEHLRKGDNLVNKP
  DERGFTPLIWASAFGEIETVRFLLEWGADPHILAKERESALSLASTGGYTDIVGLLLERD
  VDINIYDWNGGTPLLYAVRGNHVKCVEALLARGADLTTEADSGYTPMDLAVALGYRKVQQ
  VIENHILKLFQSNLVPADPE
• Function: Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator/CIITA. May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters. May also potentiate the activation of RAF1; Isoform 2 is not involved in the positive regulation of MHC class II genes.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  Tuberculosis (hsa05152)
  Primary immunodeficiency (hsa05340)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
MHC class II deficiency	DISWMI0G	Definitive	Autosomal recessive	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[2]
Large cell lymphoma	DISYZHCP	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Chronic renal failure	DISGG7K6	moderate	Biomarker	[4]
End-stage renal disease	DISXA7GG	moderate	Biomarker	[4]
Bladder transitional cell carcinoma	DISNL46A	Disputed	Genetic Variation	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	DNA-binding protein RFXANK (RFXANK) affects the response to substance of Paclitaxel.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DNA-binding protein RFXANK (RFXANK).	[6]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA-binding protein RFXANK (RFXANK).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA-binding protein RFXANK (RFXANK).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA-binding protein RFXANK (RFXANK).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA-binding protein RFXANK (RFXANK).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of DNA-binding protein RFXANK (RFXANK).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA-binding protein RFXANK (RFXANK).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA-binding protein RFXANK (RFXANK).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of DNA-binding protein RFXANK (RFXANK).	[14]

References

• [1] 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.
• [2] RFX-B, a MHC class II transcription factor, suppressed in human colorectal adenocarcinomas.Int J Mol Med. 2002 Mar;9(3):213-6.
• [3] Large B cell lymphoma presenting initially in bone marrow, liver and spleen: an aggressive entity associated frequently with haemophagocytic syndrome.Histopathology. 2010 Dec;57(6):785-95. doi: 10.1111/j.1365-2559.2010.03709.x.
• [4] Comparison of multiple fluid status assessment methods in patients on chronic hemodialysis.Int Urol Nephrol. 2017 Mar;49(3):525-532. doi: 10.1007/s11255-016-1473-y. Epub 2016 Dec 10.
• [5] Characterization of genes associated with different phenotypes of human bladder cancer cells.Acta Biochim Biophys Sin (Shanghai). 2006 Sep;38(9):602-10. doi: 10.1111/j.1745-7270.2006.00205.x.
• [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] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [11] 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.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.