Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83QOSI)

• DOT Name: Focadhesin (FOCAD)
• Gene Name: FOCAD
• Related Disease:
  Adult glioblastoma
  Alzheimer disease
  Astrocytoma
  Colorectal carcinoma
  Early-onset non-syndromic cataract
  Glioblastoma multiforme
  Glioma
  Neoplasm
  Liver disease, severe congenital
  Polyposis
• UniProt ID: FOCAD_HUMAN
• Pfam ID: PF12530 ; PF11229
• Sequence:
  MSDDIRKRFEFPNSLIQSQAVGHLIAAVLKENGFSEKIHQSTNQTPALNLLWEKCCSDNV
  VVRTACCEGLVALVAQDHAEFSYVLNGILNLIPSTRNTHGLIKAIMHLLQMQALKEGQGG
  EKNIQSIYTIRNHPHPLITVLEHRPDCWPVFLQQLTAFFQQCPERLEVSCIQIMAPFLWY
  LYCEPSQLQEYAKLRLALLKVLLQPQVLCDKDQPSILEQQILQLCCDIVPCLQVKDLIQT
  TEAMMFIEEVCLSLLRHPVFWKIQLTQMSLQLLCVSEVSLKITGECSSSIHLLEHSVELL
  KEDFPVELVIIGIALLLLQTPASQQKPILNLALKLLSVTEDQKIPKSSLLLVMPILQILS
  STALEDCISVDEEGPSRQQLALNLLEMIQQECYRDDHQKLSYKLVCPVTSMYGTIFTAWR
  ILEVMTDSSAASDWLASVESLLPITAVIPAPAFLLLAHLLVEDKGQNLHQILKVTTELAQ
  ADSSQVPNLIPVLMFKLGRPLEPILYNDILYTLPKLGVHKVCIGQILRIIQLLGTTPRLR
  AVTLRLLTSLWEKQDRVYPELQRFMAVSDVPSLSVGKEVQWEKLIAKAASIRDICKQRPY
  QHGADMLAAISQVLNECTKPDQATPAALVLQGLHALCQAEVVCIRSTWNALSPKLSCDTR
  PLILKTLSELFSLVPSLTVNTTEYENFKVQVLSFLWTHTQNKDPIVANAAYRSLANFSAG
  EHTILHLPEKIRPEIPIPEELDDDEDVEDVDLSVPGSCYLKLLSLTPPLVLPALEEFFTS
  LVKQEMVNMPRGIYHSALKGGARSDQGKTVAGIPNFILKMYETNKQPGLKPGLAGGMLFC
  YDVSMYQSKDGKPLNRLMASRGRSFKQTSLALVHEVHIQLSEWHRAIFLPQAWLAYMNRA
  YHAILQGRLGELELQLKHGKEEPEEVQYKKSTAWLWVRDMLTDEITKAAAKESPVVKGNA
  LLALSSLAVVVSRHEASLSSDSDGLLEVQPNFLSMKEWVSMVLDTLLVIVDSHYQPRGQL
  LSWFYYKSYSGENTASAIARSAAATALSLLVPVFIISCKEKVEEILNMLTARLPGKPSAD
  ESQAVQIHMGLALGMFLSRLCEEKLSDISGQEMNLLLMKSLDALENCCFDTSLEYNTGCI
  LGVGLVLSLMSHSSQMQSRVHVAALLRKLSAHVDDSGSQSRTFQEVLAYTLSCVCTSAFS
  AGIIEATEAEDVMNKLRLLVENSQQTSGFALALGNIVHGLSVCGHGKAEDLGSKLLPAWI
  RIVLTEGTPTMLCLAALHGMVALVGSEGDVMQLKSEAIQTSHFQGRLNEVIRTLTQVISV
  SGVIGLQSNAVWLLGHLHLSTLSSSQSRASVPTDYSYLPESSFIGAAIGFFITGGKKGPE
  SVPPSLLKVVMKPIATVGESYQYPPVNWAALLSPLMRLNFGEEIQQLCLEIMVTQAQSSQ
  NAAALLGLWVTPPLIHSLSLNTKRYLLISAPLWIKHISDEQILGFVENLMVAVFKAASPL
  GSPELCPSALHGLSQAMKLPSPAHHLWSLLSEATGKIFDLLPNKIRRKDLELYISIAKCL
  LEMTDDDANRIAQVTKSNIEKAAFVKLYLVSQGRFPLVNLTDMLSVAVQHREKEVLAWMI
  LHSLYQARIVSHANTGVLKRMEWLLELMGYIRNVAYQSTSFHNTALDKALDFFLLIFATA
  VVAWADHTAPLLLGLSASWLPWHQENGPAGPVPSFLGRSPMHRVTLQEVLTLLPNSMALL
  LQKEPWKEQTQKFIDWLFSIMESPKEALSAQSRDLLKATLLSLRVLPEFKKKAVWTRAYG
  W
• Function: Required for the maintenance of SKIC2 and SKIC3 proteostatic levels in the liver. May be involved in the regulation of RNA degradation by the exosome complex. Potential tumor suppressor in gliomas.
• Tissue Specificity: Ubiquitous. High expression in brain followed by testis, muscle, pancreas, heart, ovary, small intestine, placenta, prostate, thymus, kidney, colon, liver, lung, spleen and leukocytes. Expression is reduced in most glioblastomas and all glioblastoma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Astrocytoma	DISL3V18	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[3]
Early-onset non-syndromic cataract	DIS4VPS0	Strong	Genetic Variation	[4]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Liver disease, severe congenital	DISEPNJ3	Moderate	Autosomal recessive	[5]
Polyposis	DISZSPOK	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Focadhesin (FOCAD).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Focadhesin (FOCAD).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Focadhesin (FOCAD).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Focadhesin (FOCAD).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Focadhesin (FOCAD).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Focadhesin (FOCAD).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Focadhesin (FOCAD).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Focadhesin (FOCAD).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Focadhesin (FOCAD).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Focadhesin (FOCAD).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Focadhesin (FOCAD).	[17]

References

• [1] KIAA1797/FOCAD encodes a novel focal adhesion protein with tumour suppressor function in gliomas.Brain. 2012 Apr;135(Pt 4):1027-41. doi: 10.1093/brain/aws045. Epub 2012 Mar 16.
• [2] FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas.Acta Neuropathol. 2020 Jan;139(1):175-192. doi: 10.1007/s00401-019-02067-z. Epub 2019 Aug 31.
• [3] Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development.J Pathol. 2015 Jun;236(2):155-64. doi: 10.1002/path.4520. Epub 2015 Mar 26.
• [4] Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.Hum Mol Genet. 2014 Nov 15;23(22):6119-28. doi: 10.1093/hmg/ddu315. Epub 2014 Jun 20.
• [5] 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.
• [6] Contribution to colonic polyposis of recently proposed predisposing genes and assessment of the prevalence of NTHL1- and MSH3-associated polyposes.Hum Mutat. 2019 Nov;40(11):1910-1923. doi: 10.1002/humu.23853. Epub 2019 Jul 29.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [12] 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.
• [13] 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.
• [14] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [15] 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.
• [16] 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.
• [17] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.