Details of Drug Off-Target (DOT)

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

DOT Name Protocadherin-18 (PCDH18)
Gene Name PCDH18
Related Disease
Advanced cancer ( )
Colorectal carcinoma ( )
Head-neck squamous cell carcinoma ( )
Myocardial infarction ( )
Hepatocellular carcinoma ( )
Intellectual disability ( )
Neoplasm ( )
UniProt ID
PCD18_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6VFR
Pfam ID
PF00028 ; PF08266
Sequence
MHQMNAKMHFRFVFALLIVSFNHDVLGKNLKYRIYEEQRVGSVIARLSEDVADVLLKLPN
PSTVRFRAMQRGNSPLLVVNEDNGEISIGATIDREQLCQKNLNCSIEFDVITLPTEHLQL
FHIEVEVLDINDNSPQFSRSLIPIEISESAAVGTRIPLDSAFDPDVGENSLHTYSLSAND
FFNIEVRTRTDGAKYAELIVVRELDRELKSSYELQLTASDMGVPQRSGSSILKISISDSN
DNSPAFEQQSYIIQLLENSPVGTLLLDLNATDPDEGANGKIVYSFSSHVSPKIMETFKID
SERGHLTLFKQVDYEITKSYEIDVQAQDLGPNSIPAHCKIIIKVVDVNDNKPEININLMS
PGKEEISYIFEGDPIDTFVALVRVQDKDSGLNGEIVCKLHGHGHFKLQKTYENNYLILTN
ATLDREKRSEYSLTVIAEDRGTPSLSTVKHFTVQINDINDNPPHFQRSRYEFVISENNSP
GAYITTVTATDPDLGENGQVTYTILESFILGSSITTYVTIDPSNGAIYALRIFDHEEVSQ
ITFVVEARDGGSPKQLVSNTTVVLTIIDENDNVPVVIGPALRNNTAEITIPKGAESGFHV
TRIRAIDRDSGVNAELSCAIVAGNEENIFIIDPRSCDIHTNVSMDSVPYTEWELSVIIQD
KGNPQLHTKVLLKCMIFEYAESVTSTAMTSVSQASLDVSMIIIISLGAICAVLLVIMVLF
ATRCNREKKDTRSYNCRVAESTYQHHPKRPSRQIHKGDITLVPTINGTLPIRSHHRSSPS
SSPTLERGQMGSRQSHNSHQSLNSLVTISSNHVPENFSLELTHATPAVEQVSQLLSMLHQ
GQYQPRPSFRGNKYSRSYRYALQDMDKFSLKDSGRGDSEAGDSDYDLGRDSPIDRLLGEG
FSDLFLTDGRIPAAMRLCTEECRVLGHSDQCWMPPLPSPSSDYRSNMFIPGEEFPTQPQQ
QHPHQSLEDDAQPADSGEKKKSFSTFGKDSPNDEDTGDTSTSSLLSEMSSVFQRLLPPSL
DTYSECSEVDRSNSLERRKGPLPAKTVGYPQGVAAWAASTHFQNPTTNCGPPLGTHSSVQ
PSSKWLPAMEEIPENYEEDDFDNVLNHLNDGKHELMDASELVAEINKLLQDVRQS
Function Potential calcium-dependent cell-adhesion protein.
Tissue Specificity Expressed in all tissues, with highest expression in lung and ovary.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [2]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [1]
Myocardial infarction DIS655KI Strong Biomarker [3]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [4]
Intellectual disability DISMBNXP Limited Biomarker [5]
Neoplasm DISZKGEW Limited Biomarker [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Protocadherin-18 (PCDH18). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Protocadherin-18 (PCDH18). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protocadherin-18 (PCDH18). [9]
Azacitidine DMTA5OE Approved Azacitidine decreases the expression of Protocadherin-18 (PCDH18). [10]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Protocadherin-18 (PCDH18). [11]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of Protocadherin-18 (PCDH18). [12]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Protocadherin-18 (PCDH18). [14]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Protocadherin-18 (PCDH18). [16]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Drug(s)
2 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 Protocadherin-18 (PCDH18). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Protocadherin-18 (PCDH18). [15]
------------------------------------------------------------------------------------

References

1 Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.Tumour Biol. 2018 May;40(5):1010428318780859. doi: 10.1177/1010428318780859.
2 PCDH18 is frequently inactivated by promoter methylation in colorectal cancer.Sci Rep. 2017 Jun 6;7(1):2819. doi: 10.1038/s41598-017-03133-w.
3 Gene expression profile analysis of aortic vascular smooth muscle cells reveals upregulation of cadherin genes in myocardial infarction patients.Physiol Genomics. 2018 Aug 1;50(8):648-657. doi: 10.1152/physiolgenomics.00042.2017. Epub 2018 May 18.
4 Sporadic PCDH18 somatic mutations in EpCAM-positive hepatocellular carcinoma.Cancer Cell Int. 2017 Oct 23;17:94. doi: 10.1186/s12935-017-0467-x. eCollection 2017.
5 A single gene deletion on 4q28.3: PCDH18--a new candidate gene for intellectual disability?.Eur J Med Genet. 2012 Apr;55(4):274-7. doi: 10.1016/j.ejmg.2012.02.010. Epub 2012 Mar 6.
6 The Inhibitory Signaling Receptor Protocadherin-18 Regulates Tumor-Infiltrating CD8(+) T-cell Function.Cancer Immunol Res. 2017 Oct;5(10):920-928. doi: 10.1158/2326-6066.CIR-17-0187. Epub 2017 Sep 5.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
9 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.
10 The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
11 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.
12 Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
13 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.
14 Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
15 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.
16 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.