Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIUZ0C7)

DOT Name CSC1-like protein 1 (TMEM63A)
Synonyms Transmembrane protein 63A
Gene Name TMEM63A
Related Disease
Gastric cancer ( )
Gastric neoplasm ( )
Hereditary diffuse gastric adenocarcinoma ( )
Leukodystrophy ( )
Leukodystrophy, hypomyelinating, 19, transient infantile ( )
UniProt ID
CSCL1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8EHW; 8GRS
Pfam ID
PF14703 ; PF02714 ; PF13967
Sequence
MMDSPFLELWQSKAVSIREQLGLGDRPNDSYCYNSAKNSTVLQGVTFGGIPTVLLIDVSC
FLFLILVFSIIRRRFWDYGRIALVSEADSESRFQRLSSTSSSGQQDFENELGCCPWLTAI
FRLHDDQILEWCGEDAIHYLSFQRHIIFLLVVVSFLSLCVILPVNLSGDLLDKDPYSFGR
TTIANLQTDNDLLWLHTIFAVIYLFLTVGFMRHHTQSIKYKEENLVRRTLFITGLPRDAR
KETVESHFRDAYPTCEVVDVQLCYNVAKLIYLCKEKKKTEKSLTYYTNLQVKTGQRTLIN
PKPCGQFCCCEVLGCEWEDAISYYTRMKDRLLERITEEERHVQDQPLGMAFVTFQEKSMA
TYILKDFNACKCQSLQCKGEPQPSSHSRELYTSKWTVTFAADPEDICWKNLSIQGLRWWL
QWLGINFTLFLGLFFLTTPSIILSTMDKFNVTKPIHALNNPIISQFFPTLLLWSFSALLP
SIVYYSTLLESHWTKSGENQIMMTKVYIFLIFMVLILPSLGLTSLDFFFRWLFDKTSSEA
SIRLECVFLPDQGAFFVNYVIASAFIGNGMELLRLPGLILYTFRMIMAKTAADRRNVKQN
QAFQYEFGAMYAWMLCVFTVIVAYSITCPIIAPFGLIYILLKHMVDRHNLYFVYLPAKLE
KGIHFAAVNQALAAPILCLFWLYFFSFLRLGMKAPATLFTFLVLLLTILVCLAHTCFGCF
KHLSPLNYKTEEPASDKGSEAEAHMPPPFTPYVPRILNGLASERTALSPQQQQQQTYGAI
HNISGTIPGQCLAQSATGSVAAAPQEA
Function Acts as an osmosensitive calcium-permeable cation channel. Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion.
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Gastric cancer DISXGOUK Strong Biomarker [1]
Gastric neoplasm DISOKN4Y Strong Biomarker [1]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Strong Biomarker [1]
Leukodystrophy DISVY1TT Strong Biomarker [2]
Leukodystrophy, hypomyelinating, 19, transient infantile DIS290GP Strong Autosomal dominant [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of CSC1-like protein 1 (TMEM63A). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of CSC1-like protein 1 (TMEM63A). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of CSC1-like protein 1 (TMEM63A). [6]
Marinol DM70IK5 Approved Marinol increases the expression of CSC1-like protein 1 (TMEM63A). [7]
Selenium DM25CGV Approved Selenium increases the expression of CSC1-like protein 1 (TMEM63A). [8]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of CSC1-like protein 1 (TMEM63A). [8]
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 decreases the expression of CSC1-like protein 1 (TMEM63A). [9]
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⏷ Show the Full List of 7 Drug(s)

References

1 A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
2 Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy.Am J Hum Genet. 2019 Nov 7;105(5):996-1004. doi: 10.1016/j.ajhg.2019.09.011. Epub 2019 Oct 3.
3 Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling. J Clin Invest. 2013 Oct;123(10):4208-18. doi: 10.1172/JCI67119. Epub 2013 Sep 3.
4 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.
5 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.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
8 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.
9 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.