Details of Drug Off-Target (DOT)

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

• DOT Name: FXYD domain-containing ion transport regulator 6 (FXYD6)
• Synonyms: Phosphohippolin
• Gene Name: FXYD6
• Related Disease:
  Acute myelogenous leukaemia
  Alzheimer disease
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: FXYD6_HUMAN
• PDB ID: 8D3U; 8D3V; 8D3W; 8D3X; 8D3Y
• Pfam ID: PF02038
• Sequence:
  MELVLVFLCSLLAPMVLASAAEKEKEMDPFHYDYQTLRIGGLVFAVVLFSVGILLILSRR
  CKCSFNQKPRAPGDEEAQVENLITANATEPQKAEN
• Reactome Pathway:
  Ion transport by P-type ATPases (R-HSA-936837)
  Potential therapeutics for SARS (R-HSA-9679191)
  Ion homeostasis (R-HSA-5578775)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[3]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of FXYD domain-containing ion transport regulator 6 (FXYD6).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FXYD domain-containing ion transport regulator 6 (FXYD6).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of FXYD domain-containing ion transport regulator 6 (FXYD6).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of FXYD domain-containing ion transport regulator 6 (FXYD6).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of FXYD domain-containing ion transport regulator 6 (FXYD6).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of FXYD domain-containing ion transport regulator 6 (FXYD6).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of FXYD domain-containing ion transport regulator 6 (FXYD6).	[9]

1 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 increases the methylation of FXYD domain-containing ion transport regulator 6 (FXYD6).	[10]

References

• [1] Discovery of epigenetically silenced genes in acute myeloid leukemias.Leukemia. 2007 May;21(5):1026-34. doi: 10.1038/sj.leu.2404611. Epub 2007 Mar 1.
• [2] A serial analysis of gene expression profile of the Alzheimer's disease Tg2576 mouse model.Neurotox Res. 2010 May;17(4):360-79. doi: 10.1007/s12640-009-9112-3. Epub 2009 Sep 16.
• [3] MiR-372-3p inhibits the growth and metastasis of osteosarcoma cells by targeting FXYD6.Eur Rev Med Pharmacol Sci. 2018 Jan;22(1):62-69. doi: 10.26355/eurrev_201801_14101.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] 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.