Details of Drug Off-Target (DOT)

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

• DOT Name: Rhox homeobox family member 2 (RHOXF2)
• Synonyms: Paired-like homeobox protein PEPP-2; Testis homeobox gene 1
• Gene Name: RHOXF2
• Related Disease:
  Advanced cancer
  leukaemia
  Leukemia
  Lung cancer
  Testicular cancer
  Neoplasm of esophagus
• UniProt ID: RHXF2_HUMAN
• Pfam ID: PF00046
• Sequence:
  MEPPDQCSQYMTSLLSPAVDDEKELQDMNAMVLSLTEEVKEEEEDAQPEPEQGTAAGEKL
  KSAGAQGGEEKDGGGEEKDGGGAGVPGHLWEGDLEGTSGSDGNVEDSDQSEKEPGQQYSR
  PQGAVGGLEPGNAQQPNVHAFTPLQLQELERIFQREQFPSEFLRRRLARSMNVTELAVQI
  WFENRRAKWRRHQRALMARNMLPFMAVGQPVMVTAAEAITAPLFISGMRDDYFWDHSHSS
  SLCFPMPPFPPPSLPLPLMLLPPMPPAGQAEFGPFPFVIVPSFTFPNV
• Function: Transcription factor maybe involved in reproductive processes. Modulates expression of target genes encoding proteins involved in processes relevant to spermatogenesis.
• Tissue Specificity: Testis. Not detected in epididymis nor placenta. In testis, mainly expressed in germ cells, but also detected in somatic cells such as Sertoli cells, Leydig cells and peritubular cells .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
leukaemia	DISS7D1V	Strong	Biomarker	[1]
Leukemia	DISNAKFL	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[2]
Neoplasm of esophagus	DISOLKAQ	Limited	Biomarker	[3]

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 Rhox homeobox family member 2 (RHOXF2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Rhox homeobox family member 2 (RHOXF2).	[5]

References

• [1] Identification of RHOXF2 (PEPP2) as a cancer-promoting gene by expression cloning.Int J Oncol. 2012 Jan;40(1):93-8. doi: 10.3892/ijo.2011.1173. Epub 2011 Aug 19.
• [2] Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies.PLoS One. 2016 Jan 19;11(1):e0146371. doi: 10.1371/journal.pone.0146371. eCollection 2016.
• [3] Promotion of cellular senescence by THG-1/TSC22D4 knockout through activation of JUNB.Biochem Biophys Res Commun. 2020 Feb 19;522(4):897-902. doi: 10.1016/j.bbrc.2019.11.145. Epub 2019 Dec 3.
• [4] 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.
• [5] Three epigenetic drugs up-regulate homeobox gene Rhox5 in cancer cells through overlapping and distinct molecular mechanisms. Mol Pharmacol. 2009 Nov;76(5):1072-81. doi: 10.1124/mol.109.056291. Epub 2009 Aug 13.