Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2LKDD0)

DOT Name Thrombospondin-type laminin G domain and EAR repeat-containing protein (TSPEAR)
Synonyms TSP-EAR
Gene Name TSPEAR
Related Disease
Deafness ( )
Dystonia ( )
Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis ( )
Epilepsy ( )
Hearing loss, autosomal recessive ( )
Autosomal recessive nonsyndromic hearing loss 98 ( )
Nonsyndromic genetic hearing loss ( )
Alopecia ( )
UniProt ID
TSEAR_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF03736
Sequence
MSALLSLCFVLPLAAPGHGTQGWEPCTDLRPLDILAEVVPSDGATSGIRIVQVHGARGLQ
LSVAAPRTMSFPASRIFSQCDLFPEEFSIVVTLRVPNLPPKRNEYLLTVVAEESDLLLLG
LRLSPAQLHFLFLREDTAGAWQTRVSFRSPALVDGRWHTLVLAVSAGVFSLTTDCGLPVD
IMADVPFPATLSVKGARFFVGSRRRAKGLFMGLVRQLVLLPGSDATPRLCPSRNAPLAVL
SIPRVLQALTGKPEDNEVLKYPYETNIRVTLGPQPPCTEVEDAQFWFDASRKGLYLCVGN
EWVSVLAAKERLDYVEEHQNLSTNSETLGIEVFRIPQVGLFVATANRKATSAVYKWTEEK
FVSYQNIPTHQAQAWRHFTIGKKIFLAVANFEPDEKGQEFSVIYKWSHRKLKFTPYQSIA
THSARDWEAFEVDGEHFLAVANHREGDNHNIDSVIYKWNPATRLFEANQTIATSGAYDWE
FFSVGPYSFLVVANTFNGTSTKVHSHLYIRLLGSFQLFQSFPTFGAADWEVFQIGERIFL
AVANSHSYDVEMQVQNDSYVINSVIYELNVTAQAFVKFQDILTCSALDWEFFSVGEDYFL
VVANSFDGRTFSVNSIIYRWQGYEGFVAVHSLPTVGCRDWEAFSTTAGAYLIYSSAKEPL
SRVLRLRTR
Function Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway. May play a role in development or function of the auditory system.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Deafness DISKCLH4 Strong Biomarker [1]
Dystonia DISJLFGW Strong Genetic Variation [2]
Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis DISGEI76 Strong Autosomal recessive [2]
Epilepsy DISBB28L Strong Biomarker [3]
Hearing loss, autosomal recessive DIS8G9R9 Supportive Autosomal recessive [1]
Autosomal recessive nonsyndromic hearing loss 98 DISFFTMA Disputed Autosomal recessive [1]
Nonsyndromic genetic hearing loss DISZX61P Disputed Autosomal recessive [4]
Alopecia DIS37HU4 Limited Genetic Variation [5]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Thrombospondin-type laminin G domain and EAR repeat-containing protein (TSPEAR). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Thrombospondin-type laminin G domain and EAR repeat-containing protein (TSPEAR). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Thrombospondin-type laminin G domain and EAR repeat-containing protein (TSPEAR). [11]
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3 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 laminin G domain and EAR repeat-containing protein (TSPEAR). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Thrombospondin-type laminin G domain and EAR repeat-containing protein (TSPEAR). [8]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Thrombospondin-type laminin G domain and EAR repeat-containing protein (TSPEAR). [9]
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References

1 Defect in the gene encoding the EAR/EPTP domain-containing protein TSPEAR causes DFNB98 profound deafness. Hum Mol Genet. 2012 Sep 1;21(17):3835-44. doi: 10.1093/hmg/dds212. Epub 2012 Jun 7.
2 Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis. PLoS Genet. 2016 Oct 13;12(10):e1006369. doi: 10.1371/journal.pgen.1006369. eCollection 2016 Oct.
3 Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3.Mol Psychiatry. 2006 Feb;11(2):134-42. doi: 10.1038/sj.mp.4001759.
4 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
5 Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
6 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.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
11 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.