Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2QHEQ6)

• DOT Name: Protein FAM210B, mitochondrial (FAM210B)
• Gene Name: FAM210B
• Related Disease:
  Advanced cancer
  Epithelial ovarian cancer
  Metastatic malignant neoplasm
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: F210B_HUMAN
• Pfam ID: PF06916
• Sequence:
  MAGLLALLGPAGRVGARVRPRATWLLGATAPCAPPPLALALLPPRLDARLLRTARGDCRG
  HQDPSQATGTTGSSVSCTEEKKQSKSQQLKKIFQEYGTVGVSLHIGISLISLGIFYMVVS
  SGVDMPAILLKLGFKESLVQSKMAAGTSTFVVAYAIHKLFAPVRISITLVSVPLIVRYFR
  KVGFFKPPAAKP
• Function: Plays a role in erythroid differentiation. Involved in cell proliferation and tumor cell growth suppression. Involved in the metabolic reprogramming of cancer cells in a PDK4-dependent manner.
• Tissue Specificity: Expressed in late erythroblast differentiation stages . Underexpressed in ovarian cancer epithelia cells compared with normal human ovarian surface epithelia .

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]

18 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 Protein FAM210B, mitochondrial (FAM210B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FAM210B, mitochondrial (FAM210B).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein FAM210B, mitochondrial (FAM210B).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein FAM210B, mitochondrial (FAM210B).	[9]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Protein FAM210B, mitochondrial (FAM210B).	[10]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[10]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein FAM210B, mitochondrial (FAM210B).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein FAM210B, mitochondrial (FAM210B).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein FAM210B, mitochondrial (FAM210B).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein FAM210B, mitochondrial (FAM210B).	[17]

References

• [1] Loss of the novel mitochondrial protein FAM210B promotes metastasis via PDK4-dependent metabolic reprogramming.Cell Death Dis. 2017 Jun 8;8(6):e2870. doi: 10.1038/cddis.2017.273.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [14] 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.
• [15] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.