Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3SC14T)

• DOT Name: Rhox homeobox family member 1 (RHOXF1)
• Synonyms: Ovary-, testis- and epididymis-expressed gene protein; Paired-like homeobox protein PEPP-1
• Gene Name: RHOXF1
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: RHXF1_HUMAN
• Pfam ID: PF00046
• Sequence:
  MARSLVHDTVFYCLSVYQVKISPTPQLGAASSAEGHVGQGAPGLMGNMNPEGGVNHENGM
  NRDGGMIPEGGGGNQEPRQQPQPPPEEPAQAAMEGPQPENMQPRTRRTKFTLLQVEELES
  VFRHTQYPDVPTRRELAENLGVTEDKVRVWFKNKRARCRRHQRELMLANELRADPDDCVY
  IVVD
• Function: Transcription factor maybe involved in reproductive processes. Modulates expression of target genes encoding proteins involved in processes relevant to spermatogenesis.
• Tissue Specificity: Ovary, testis and epididymis. Also detected in the prostate and the mammary gland. Expressed in many tumor cell lines derived from acute lymphocytic leukemia, prostate, endometrial adenocarcinoma, melanoma, bladder carcinoma, colon carcinoma, erythroleukemia and breast carcinoma. Not expressed in 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	moderate	Biomarker	[1]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[1]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Rhox homeobox family member 1 (RHOXF1).	[2]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Rhox homeobox family member 1 (RHOXF1).	[4]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Rhox homeobox family member 1 (RHOXF1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rhox homeobox family member 1 (RHOXF1).	[3]

References

• [1] shRNA mediated RHOXF1 silencing influences expression of BCL2 but not CASP8 in MCF-7 and MDA-MB-231 cell lines.Asian Pac J Cancer Prev. 2012;13(11):5865-9. doi: 10.7314/apjcp.2012.13.11.5865.
• [2] 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.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] 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.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.