Details of Drug Off-Target (DOT)

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

• DOT Name: Protein FAM98A (FAM98A)
• Gene Name: FAM98A
• Related Disease:
  Endometrial carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Venous thromboembolism
• UniProt ID: FA98A_HUMAN
• Pfam ID: PF10239
• Sequence:
  MECDLMETDILESLEDLGYKGPLLEDGALSQAVSAGASSPEFTKLCAWLVSELRVLCKLE
  ENVQATNSPSEAEEFQLEVSGLLGEMNCPYLSLTSGDVTKRLLIQKNCLLLLTYLISELE
  AARMLCVNAPPKKAQEGGGSEVFQELKGICIALGMSKPPANITMFQFFSGIEKKLKETLA
  KVPPNHVGKPLLKKPMGPAHWEKIEAINQAIANEYEVRRKLLIKRLDVTVQSFGWSDRAK
  SQTEKLAKVYQPKRSVLSPKTTISVAHLLAARQDLSKILRTSSGSIREKTACAINKVLMG
  RVPDRGGRPNEIEPPPPEMPPWQKRQDGPQQQTGGRGGGRGGYEHSSYGGRGGHEQGGGR
  GGRGGYDHGGRGGGRGNKHQGGWTDGGSGGGGGYQDGGYRDSGFQPGGYHGGHSSGGYQG
  GGYGGFQTSSSYTGSGYQGGGYQQDNRYQDGGHHGDRGGGRGGRGGRGGRGGRAGQGGGW
  GGRGSQNYHQGGQFEQHFQHGGYQYNHSGFGQGRHYTS
• Function: Positively stimulates PRMT1-induced protein arginine methylation. Involved in skeletal homeostasis. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts.
• Tissue Specificity: Expressed strongly in colorectal cancer cells . Expressed strongly in colorectal cancer tissues compared to wild-type colon samples (at protein level) . Expressed strongly in colorectal cancer tissues compared to wild-type colon samples .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[3]

13 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 FAM98A (FAM98A).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein FAM98A (FAM98A).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FAM98A (FAM98A).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein FAM98A (FAM98A).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein FAM98A (FAM98A).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein FAM98A (FAM98A).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein FAM98A (FAM98A).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein FAM98A (FAM98A).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FAM98A (FAM98A).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FAM98A (FAM98A).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein FAM98A (FAM98A).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein FAM98A (FAM98A).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Protein FAM98A (FAM98A).	[16]

References

• [1] FAM98A promotes cancer progression in endometrial carcinoma.Mol Cell Biochem. 2019 Sep;459(1-2):131-139. doi: 10.1007/s11010-019-03556-1. Epub 2019 May 21.
• [2] FAM98A promotes proliferation of non-small cell lung cancer cells via the P38-ATF2 signaling pathway.Cancer Manag Res. 2018 Jul 27;10:2269-2278. doi: 10.2147/CMAR.S163323. eCollection 2018.
• [3] Identification of unique venous thromboembolism-susceptibility variants in African-Americans.Thromb Haemost. 2017 Apr 3;117(4):758-768. doi: 10.1160/TH16-08-0652. Epub 2017 Feb 16.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] 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.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] 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.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.