Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRRS828)

• DOT Name: Fatty acid hydroxylase domain-containing protein 2 (FAXDC2)
• Gene Name: FAXDC2
• Related Disease:
  Juvenile idiopathic arthritis
  Schizophrenia
• UniProt ID: FXDC2_HUMAN
• Pfam ID: PF04116
• Sequence:
  MKGEAGHMLHNEKSKQEGHIWGSMRRTAFILGSGLLSFVAFWNSVTWHLQRFWGASGYFW
  QAQWERLLTTFEGKEWILFFIGAIQVPCLFFWSFNGLLLVVDTTGKPNFISRYRIQVGKN
  EPVDPVKLRQSIRTVLFNQCMISFPMVVFLYPFLKWWRDPCRRELPTFHWFLLELAIFTL
  IEEVLFYYSHRLLHHPTFYKKIHKKHHEWTAPIGVISLYAHPIEHAVSNMLPVIVGPLVM
  GSHLSSITMWFSLALIITTISHCGYHLPFLPSPEFHDYHHLKFNQCYGVLGVLDHLHGTD
  TMFKQTKAYERHVLLLGFTPLSESIPDSPKRME
• Function: Promotes megakaryocyte differentiation by enhancing ERK phosphorylation and up-regulating RUNX1 expression.
• Tissue Specificity: Down-regulated in primary acute myeloid leukemia (AML) patients.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	No Known	Unknown	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[12]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[13]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[10]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[19]

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 decreases the methylation of Fatty acid hydroxylase domain-containing protein 2 (FAXDC2).	[16]

References

• [1] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [2] Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes. PLoS One. 2014 Nov 24;9(11):e112745. doi: 10.1371/journal.pone.0112745. eCollection 2014.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [15] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [16] 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.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.