Details of Drug Off-Target (DOT)

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

• DOT Name: Thrombospondin type-1 domain-containing protein 1 (THSD1)
• Synonyms: Transmembrane molecule with thrombospondin module
• Gene Name: THSD1
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
  Non-immune hydrops fetalis
  Advanced cancer
  Aneurysm, intracranial berry, 12
  Carcinoma of esophagus
  Esophageal squamous cell carcinoma
  Hemangioma
  Lymphatic malformation 13
  Neoplasm
  Subarachnoid hemorrhage
  Intracranial berry aneurysm
  Multiple congenital anomalies/dysmorphic syndrome
• UniProt ID: THSD1_HUMAN
• Pfam ID: PF00090
• Sequence:
  MKPMLKDFSNLLLVVLCDYVLGEAEYLLLREPGHVALSNDTVYVDFQYFDGANGTLRNVS
  VLLLEANTNQTVTTKYLLTNQSQGTLKFECFYFKEAGDYWFTMTPEATDNSTPFPWWEKS
  AFLKVEWPVFHVDLNRSAKAAEGTFQVGLFTSQPLCPFPVDKPNIVVDVIFTNSLPEARR
  NSRQPLEIRTSKRTELAQGQWVEFGCAPLGPEAYVTVVLKLLGRDSVITSTGPIDLAQKF
  GYKLVMVPELTCESGVEVTVLPPPCTFVQGVVTVFKEAPRYPGKRTIHLAENSLPLGERR
  TIFNCTLFDMGKNKYCFDFGISSRSHFSAKEECMLIQRNTETWGLWQPWSQCSATCGDGV
  RERRRVCLTSFPSSPVCPGMSLEASLCSLEECAAFQPSSPSPLQPQGPVKSNNIVTVTGI
  SLCLFIIIATVLITLWRRFGRPAKCSTPARHNSIHSPSFRKNSDEENICELSEQRGSFSD
  GGDGPTGSPGDTGIPLTYRRSGPVPPEDDASGSESFQSNAQKIIPPLFSYRLAQQQLKEM
  KKKGLTETTKVYHVSQSPLTDTAIDAAPSAPLDLESPEEAAANKFRIKSPFPEQPAVSAG
  ERPPSRLDLNVTQASCAISPSQTLIRKSQARHVGSRGGPSERSHARNAHFRRTASFHEAR
  QARPFRERSMSTLTPRQAPAYSSRTRTCEQAEDRFRPQSRGAHLFPEKLEHFQEASGTRG
  PLNPLPKSYTLGQPLRKPDLGDHQAGLVAGIERTEPHRARRGPSPSHKSVSRKQSSPISP
  KDNYQRVSSLSPSQCRKDKCQSFPTHPEFAFYDNTSFGLTEAEQRMLDLPGYFGSNEEDE
  TTSTLSVEKLVI
• Function: Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.
• Reactome Pathway:
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Defective B3GALTL causes PpS (R-HSA-5083635)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Posttranslational Modification	[1]
Non-immune hydrops fetalis	DISPUY8C	Definitive	Autosomal recessive	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Aneurysm, intracranial berry, 12	DISS2440	Strong	Autosomal dominant	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[3]
Hemangioma	DISDCGAG	Strong	Genetic Variation	[5]
Lymphatic malformation 13	DISP5YOV	Strong	Autosomal recessive	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Subarachnoid hemorrhage	DISI7I8Y	moderate	Genetic Variation	[6]
Intracranial berry aneurysm	DISJYQ0R	Supportive	Autosomal dominant	[4]
Multiple congenital anomalies/dysmorphic syndrome	DIS0LF2K	Limited	Autosomal recessive	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[14]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Thrombospondin type-1 domain-containing protein 1 (THSD1).	[15]

References

• [1] Genome-wide screening for methylation-silenced genes in colorectal cancer.Int J Oncol. 2012 Aug;41(2):490-6. doi: 10.3892/ijo.2012.1500. Epub 2012 May 30.
• [2] Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families. Genome Biol. 2015 Jun 3;16(1):116. doi: 10.1186/s13059-015-0681-6.
• [3] Monochromosome transfer and microarray analysis identify a critical tumor-suppressive region mapping to chromosome 13q14 and THSD1 in esophageal carcinoma.Mol Cancer Res. 2008 Apr;6(4):592-603. doi: 10.1158/1541-7786.MCR-07-0154.
• [4] THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Stroke. 2016 Dec;47(12):3005-3013. doi: 10.1161/STROKEAHA.116.014161. Epub 2016 Nov 15.
• [5] A recessive truncating variant in thrombospondin-1 domain containing protein 1 gene THSD1 is the underlying cause of nonimmune hydrops fetalis, congenital cardiac defects, and haemangiomas in four patients from a consanguineous family.Am J Med Genet A. 2018 Sep;176(9):1996-2003. doi: 10.1002/ajmg.a.40424. Epub 2018 Jul 28.
• [6] The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent Focal Adhesion Assembly.Cell Physiol Biochem. 2017;43(6):2200-2211. doi: 10.1159/000484298. Epub 2017 Oct 25.
• [7] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] 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.
• [13] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.