Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7249HH)

DOT Name Thrombospondin type-1 domain-containing protein 7A (THSD7A)
Gene Name THSD7A
Related Disease
Chronic renal failure ( )
Autoimmune disease ( )
Bipolar depression ( )
Bipolar disorder ( )
Coronary heart disease ( )
Esophageal squamous cell carcinoma ( )
Focal segmental glomerulosclerosis ( )
Glaucoma/ocular hypertension ( )
Hyperlipidemia ( )
Macular corneal dystrophy ( )
Neoplasm ( )
Nephropathy ( )
Nephrotic syndrome ( )
Obesity ( )
Open-angle glaucoma ( )
Osteoporosis ( )
Ovarian neoplasm ( )
Acute myelogenous leukaemia ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Neurofibroma ( )
Neurofibromatosis type 1 ( )
Schwannoma ( )
Asthma ( )
Benign neoplasm ( )
Rectal carcinoma ( )
UniProt ID
THS7A_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF19030 ; PF19028 ; PF00090
Sequence
MGLQARRWASGSRGAAGPRRGVLQLLPLPLPLPLLLLLLLRPGAGRAAAQGEAEAPTLYL
WKTGPWGRCMGDECGPGGIQTRAVWCAHVEGWTTLHTNCKQAERPNNQQNCFKVCDWHKE
LYDWRLGPWNQCQPVISKSLEKPLECIKGEEGIQVREIACIQKDKDIPAEDIICEYFEPK
PLLEQACLIPCQQDCIVSEFSAWSECSKTCGSGLQHRTRHVVAPPQFGGSGCPNLTEFQV
CQSSPCEAEELRYSLHVGPWSTCSMPHSRQVRQARRRGKNKEREKDRSKGVKDPEARELI
KKKRNRNRQNRQENKYWDIQIGYQTREVMCINKTGKAADLSFCQQEKLPMTFQSCVITKE
CQVSEWSEWSPCSKTCHDMVSPAGTRVRTRTIRQFPIGSEKECPEFEEKEPCLSQGDGVV
PCATYGWRTTEWTECRVDPLLSQQDKRRGNQTALCGGGIQTREVYCVQANENLLSQLSTH
KNKEASKPMDLKLCTGPIPNTTQLCHIPCPTECEVSPWSAWGPCTYENCNDQQGKKGFKL
RKRRITNEPTGGSGVTGNCPHLLEAIPCEEPACYDWKAVRLGNCEPDNGKECGPGTQVQE
VVCINSDGEEVDRQLCRDAIFPIPVACDAPCPKDCVLSTWSTWSSCSHTCSGKTTEGKQI
RARSILAYAGEEGGIRCPNSSALQEVRSCNEHPCTVYHWQTGPWGQCIEDTSVSSFNTTT
TWNGEASCSVGMQTRKVICVRVNVGQVGPKKCPESLRPETVRPCLLPCKKDCIVTPYSDW
TSCPSSCKEGDSSIRKQSRHRVIIQLPANGGRDCTDPLYEEKACEAPQACQSYRWKTHKW
RRCQLVPWSVQQDSPGAQEGCGPGRQARAITCRKQDGGQAGIHECLQYAGPVPALTQACQ
IPCQDDCQLTSWSKFSSCNGDCGAVRTRKRTLVGKSKKKEKCKNSHLYPLIETQYCPCDK
YNAQPVGNWSDCILPEGKVEVLLGMKVQGDIKECGQGYRYQAMACYDQNGRLVETSRCNS
HGYIEEACIIPCPSDCKLSEWSNWSRCSKSCGSGVKVRSKWLREKPYNGGRPCPKLDHVN
QAQVYEVVPCHSDCNQYLWVTEPWSICKVTFVNMRENCGEGVQTRKVRCMQNTADGPSEH
VEDYLCDPEEMPLGSRVCKLPCPEDCVISEWGPWTQCVLPCNQSSFRQRSADPIRQPADE
GRSCPNAVEKEPCNLNKNCYHYDYNVTDWSTCQLSEKAVCGNGIKTRMLDCVRSDGKSVD
LKYCEALGLEKNWQMNTSCMVECPVNCQLSDWSPWSECSQTCGLTGKMIRRRTVTQPFQG
DGRPCPSLMDQSKPCPVKPCYRWQYGQWSPCQVQEAQCGEGTRTRNISCVVSDGSADDFS
KVVDEEFCADIELIIDGNKNMVLEESCSQPCPGDCYLKDWSSWSLCQLTCVNGEDLGFGG
IQVRSRPVIIQELENQHLCPEQMLETKSCYDGQCYEYKWMASAWKGSSRTVWCQRSDGIN
VTGGCLVMSQPDADRSCNPPCSQPHSYCSETKTCHCEEGYTEVMSSNSTLEQCTLIPVVV
LPTMEDKRGDVKTSRAVHPTQPSSNPAGRGRTWFLQPFGPDGRLKTWVYGVAAGAFVLLI
FIVSMIYLACKKPKKPQRRQNNRLKPLTLAYDGDADM
Function
[Thrombospondin type-1 domain-containing protein 7A]: Plays a role in actin cytoskeleton rearrangement; [Thrombospondin type-1 domain-containing protein 7A, soluble form]: The soluble form promotes endothelial cell migration and filopodia formation during sprouting angiogenesis via a FAK-dependent mechanism.
Tissue Specificity Detected on kidney podocytes along the glomerular capillary wall (at protein level).
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

27 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic renal failure DISGG7K6 Definitive Genetic Variation [1]
Autoimmune disease DISORMTM Strong Biomarker [2]
Bipolar depression DISA75FU Strong Biomarker [3]
Bipolar disorder DISAM7J2 Strong Biomarker [3]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [4]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [5]
Focal segmental glomerulosclerosis DISJNHH0 Strong Biomarker [6]
Glaucoma/ocular hypertension DISLBXBY Strong Genetic Variation [7]
Hyperlipidemia DIS61J3S Strong Biomarker [8]
Macular corneal dystrophy DISOLD0H Strong Biomarker [6]
Neoplasm DISZKGEW Strong Altered Expression [9]
Nephropathy DISXWP4P Strong Biomarker [10]
Nephrotic syndrome DISSPSC2 Strong Biomarker [11]
Obesity DIS47Y1K Strong Biomarker [12]
Open-angle glaucoma DISSZEE8 Strong Genetic Variation [13]
Osteoporosis DISF2JE0 Strong Genetic Variation [14]
Ovarian neoplasm DISEAFTY Strong Genetic Variation [15]
Acute myelogenous leukaemia DISCSPTN moderate Genetic Variation [16]
Breast cancer DIS7DPX1 moderate Altered Expression [9]
Breast carcinoma DIS2UE88 moderate Altered Expression [9]
Colorectal carcinoma DIS5PYL0 moderate Altered Expression [9]
Neurofibroma DISIJJMH moderate Biomarker [17]
Neurofibromatosis type 1 DIS53JH9 moderate Biomarker [17]
Schwannoma DISTTVLA moderate Biomarker [18]
Asthma DISW9QNS Disputed Genetic Variation [19]
Benign neoplasm DISDUXAD Limited Biomarker [20]
Rectal carcinoma DIS8FRR7 Limited Biomarker [21]
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⏷ Show the Full List of 27 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 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 Thrombospondin type-1 domain-containing protein 7A (THSD7A). [22]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [23]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [24]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [25]
Selenium DM25CGV Approved Selenium decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [26]
Progesterone DMUY35B Approved Progesterone increases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [27]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [28]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [29]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [26]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [31]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [32]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Thrombospondin type-1 domain-containing protein 7A (THSD7A). [22]
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⏷ Show the Full List of 12 Drug(s)
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 Thrombospondin type-1 domain-containing protein 7A (THSD7A). [30]
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References

1 Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study.Front Genet. 2019 May 24;10:494. doi: 10.3389/fgene.2019.00494. eCollection 2019.
2 Structure and function insights garnered from in silico modeling of the thrombospondin type-1 domain-containing 7A antigen.Proteins. 2019 Feb;87(2):136-145. doi: 10.1002/prot.25640. Epub 2018 Dec 21.
3 Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
4 Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel Susceptibility Genes for Coronary Artery Disease.Arterioscler Thromb Vasc Biol. 2018 Apr;38(4):964-975. doi: 10.1161/ATVBAHA.117.310594. Epub 2018 Feb 22.
5 Expression, prognosis and functional role of Thsd7a in esophageal squamous cell carcinoma of Kazakh patients, Xinjiang.Oncotarget. 2017 Apr 8;8(36):60539-60557. doi: 10.18632/oncotarget.16966. eCollection 2017 Sep 1.
6 Immunoadsorption in nephrotic syndrome: Where are we now and where are we going from here?.Atheroscler Suppl. 2019 Dec;40:55-60. doi: 10.1016/j.atherosclerosissup.2019.08.027. Epub 2019 Aug 17.
7 Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma.Nat Genet. 2018 Aug;50(8):1067-1071. doi: 10.1038/s41588-018-0176-y. Epub 2018 Jul 27.
8 A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous Nephropathy.J Am Soc Nephrol. 2017 Nov;28(11):3262-3277. doi: 10.1681/ASN.2017010030. Epub 2017 Aug 16.
9 Expression of THSD7A in neoplasm tissues and its relationship with proteinuria.BMC Nephrol. 2019 Aug 23;20(1):332. doi: 10.1186/s12882-019-1489-5.
10 Circulating antibodies against M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A in Chinese patients with membranous nephropathy.Int Urol Nephrol. 2019 Aug;51(8):1371-1377. doi: 10.1007/s11255-019-02146-w. Epub 2019 Jun 21.
11 Treatment of Membranous Nephropathy in Patients With THSD7A Antibodies Using Immunoadsorption.Am J Kidney Dis. 2019 Dec;74(6):849-852. doi: 10.1053/j.ajkd.2019.05.021. Epub 2019 Aug 23.
12 A novel gene THSD7A is associated with obesity.Int J Obes (Lond). 2015 Nov;39(11):1662-5. doi: 10.1038/ijo.2015.144. Epub 2015 Aug 4.
13 A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nat Commun. 2018 Jun 11;9(1):2278. doi: 10.1038/s41467-018-04555-4.
14 Association of the formiminotransferase N-terminal sub-domain containing gene and thrombospondin, type 1, domain-containing 7A gene with the prevalence of vertebral fracture in 2427 consecutive autopsy cases.J Hum Genet. 2013 Feb;58(2):109-12. doi: 10.1038/jhg.2012.145. Epub 2013 Jan 10.
15 Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecol Oncol. 2019 May;153(2):343-355. doi: 10.1016/j.ygyno.2019.02.023. Epub 2019 Mar 19.
16 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
17 THSD7A-associated membranous nephropathy in a patient with neurofibromatosis type 1.Eur J Med Genet. 2018 Feb;61(2):84-88. doi: 10.1016/j.ejmg.2017.10.014. Epub 2017 Oct 25.
18 Duodenal Schwannoma as a Rare Association With Membranous Nephropathy: A Case Report.Am J Kidney Dis. 2019 Feb;73(2):278-280. doi: 10.1053/j.ajkd.2018.09.003. Epub 2018 Nov 16.
19 Refractory THSD7A membranous nephropathy with severe asthma related toeosinophilia?"Suzuki T. Uchida D
20 VEGF-A Links Angiolymphoid Hyperplasia With Eosinophilia (ALHE) to THSD7A Membranous Nephropathy: A Report of 2 Cases.Am J Kidney Dis. 2019 Jun;73(6):880-885. doi: 10.1053/j.ajkd.2018.10.009. Epub 2018 Dec 13.
21 Thrombospondin type-1 domain-containing 7A-associated membranous nephropathy after resection of rectal cancer: a case report.BMC Nephrol. 2019 Feb 6;20(1):43. doi: 10.1186/s12882-019-1236-y.
22 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.
23 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
24 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
25 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
26 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.
27 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
28 Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
29 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.
30 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.
31 Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
32 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.