Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPC9JBM)

• DOT Name: Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP)
• Synonyms: Phytanoyl-CoA hydroxylase-associated protein 1; PAHX-AP1; PAHXAP1
• Gene Name: PHYHIP
• Related Disease:
  Adult Refsum disease
  Retinitis pigmentosa
  Adrenal adenoma
• UniProt ID: PHYIP_HUMAN
• Pfam ID: PF19281
• Sequence:
  MELLSTPHSIEINNITCDSFRISWAMEDSDLERVTHYFIDLNKKENKNSNKFKHRDVPTK
  LVAKAVPLPMTVRGHWFLSPRTEYSVAVQTAVKQSDGEYLVSGWSETVEFCTGDYAKEHL
  AQLQEKAEQIAGRMLRFSVFYRNHHKEYFQHARTHCGNMLQPYLKDNSGSHGSPTSGMLH
  GVFFSCNTEFNTGQPPQDSPYGRWRFQIPAQRLFNPSTNLYFADFYCMYTAYHYAILVLA
  PKGSLGDRFCRDRLPLLDIACNKFLTCSVEDGELVFRHAQDLILEIIYTEPVDLSLGTLG
  EISGHQLMSLSTADAKKDPSCKTCNISVGR
• Function: Its interaction with PHYH suggests a role in the development of the central system.
• Tissue Specificity: Highly expressed in the brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult Refsum disease	DISU2BLL	Strong	Biomarker	[1]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[1]
Adrenal adenoma	DISC2UN8	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Phytanoyl-CoA hydroxylase-interacting protein (PHYHIP).	[8]

References

• [1] Identification of a brain specific protein that associates with a refsum disease gene product, phytanoyl-CoA alpha-hydroxylase.Brain Res Mol Brain Res. 2000 Feb 22;75(2):237-47. doi: 10.1016/s0169-328x(99)00304-6.
• [2] Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.J Clin Endocrinol Metab. 2011 Jul;96(7):E1206-11. doi: 10.1210/jc.2010-2143. Epub 2011 May 11.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.