Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1HD6CF)

• DOT Name: Retina and anterior neural fold homeobox protein 2 (RAX2)
• Synonyms: Q50-type retinal homeobox protein; Retina and anterior neural fold homeobox-like protein 1
• Gene Name: RAX2
• Related Disease:
  Cone-rod dystrophy 2
  Cone-rod dystrophy 11
  Inherited retinal dystrophy
  Obesity
  Retinitis pigmentosa 95
  Retinopathy
  Retinitis pigmentosa
  Cone-rod dystrophy
  Retinal degeneration
• UniProt ID: RAX2_HUMAN
• Pfam ID: PF00046
• Sequence:
  MFLSPGEGPATEGGGLGPGEEAPKKKHRRNRTTFTTYQLHQLERAFEASHYPDVYSREEL
  AAKVHLPEVRVQVWFQNRRAKWRRQERLESGSGAVAAPRLPEAPALPFARPPAMSLPLEP
  WLGPGPPAVPGLPRLLGPGPGLQASFGPHAFAPTFADGFALEEASLRLLAKEHAQALDRA
  WPPA
• Function: May be involved in modulating the expression of photoreceptor specific genes. Binds to the Ret-1 and Bat-1 element within the rhodopsin promoter.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy 2	DISX2RWY	Definitive	GermlineCausalMutation	[1]
Cone-rod dystrophy 11	DISI8BH2	Strong	Autosomal dominant	[2]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[1]
Obesity	DIS47Y1K	Strong	Genetic Variation	[3]
Retinitis pigmentosa 95	DIS4ABQE	Strong	Autosomal recessive	[4]
Retinopathy	DISB4B0F	Strong	Genetic Variation	[4]
Retinitis pigmentosa	DISCGPY8	Moderate	Autosomal recessive	[4]
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[5]
Retinal degeneration	DISM1JHQ	Limited	Biomarker	[5]

3 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 Retina and anterior neural fold homeobox protein 2 (RAX2).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Retina and anterior neural fold homeobox protein 2 (RAX2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Retina and anterior neural fold homeobox protein 2 (RAX2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Retina and anterior neural fold homeobox protein 2 (RAX2).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Retina and anterior neural fold homeobox protein 2 (RAX2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Retina and anterior neural fold homeobox protein 2 (RAX2).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Retina and anterior neural fold homeobox protein 2 (RAX2).	[11]

References

• [1] Autosomal Dominant Retinal Dystrophy With Electronegative Waveform Associated With a Novel RAX2 Mutation.JAMA Ophthalmol. 2015 Jun;133(6):653-61. doi: 10.1001/jamaophthalmol.2015.0357.
• [2] The chicken RaxL gene plays a role in the initiation of photoreceptor differentiation. Development. 2002 Dec;129(23):5363-75. doi: 10.1242/dev.00114.
• [3] Genome-wide analysis reveals that altered methylation in specific CpG loci is associated with childhood obesity.J Cell Biochem. 2018 Sep;119(9):7490-7497. doi: 10.1002/jcb.27059. Epub 2018 May 24.
• [4] Biallelic sequence and structural variants in RAX2 are a novel cause for autosomal recessive inherited retinal disease. Genet Med. 2019 Jun;21(6):1319-1329. doi: 10.1038/s41436-018-0345-5. Epub 2018 Oct 31.
• [5] QRX, a novel homeobox gene, modulates photoreceptor gene expression. Hum Mol Genet. 2004 May 15;13(10):1025-40. doi: 10.1093/hmg/ddh117. Epub 2004 Mar 17.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [12] 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.