Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2VANLI)

DOT Name Protocadherin-12 (PCDH12)
Synonyms Vascular cadherin-2; Vascular endothelial cadherin-2; VE-cad-2; VE-cadherin-2
Gene Name PCDH12
Related Disease
Diencephalic-mesencephalic junction dysplasia syndrome 1 ( )
Alcohol dependence ( )
Cerebellar ataxia ( )
Epilepsy ( )
Isolated congenital microcephaly ( )
Bipolar disorder ( )
Intellectual disability ( )
Schizoaffective disorder ( )
Schizophrenia ( )
Diencephalic-mesencephalic junction dysplasia ( )
Dystonia ( )
UniProt ID
PCD12_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00028 ; PF08266
Sequence
MMQLLQLLLGLLGPGGYLFLLGDCQEVTTLTVKYQVSEEVPSGTVIGKLSQELGREERRR
QAGAAFQVLQLPQALPIQVDSEEGLLSTGRRLDREQLCRQWDPCLVSFDVLATGDLALIH
VEIQVLDINDHQPRFPKGEQELEISESASLRTRIPLDRALDPDTGPNTLHTYTLSPSEHF
ALDVIVGPDETKHAELIVVKELDREIHSFFDLVLTAYDNGNPPKSGTSLVKVNVLDSNDN
SPAFAESSLALEIQEDAAPGTLLIKLTATDPDQGPNGEVEFFLSKHMPPEVLDTFSIDAK
TGQVILRRPLDYEKNPAYEVDVQARDLGPNPIPAHCKVLIKVLDVNDNIPSIHVTWASQP
SLVSEALPKDSFIALVMADDLDSGHNGLVHCWLSQELGHFRLKRTNGNTYMLLTNATLDR
EQWPKYTLTLLAQDQGLQPLSAKKQLSIQISDINDNAPVFEKSRYEVSTRENNLPSLHLI
TIKAHDADLGINGKVSYRIQDSPVAHLVAIDSNTGEVTAQRSLNYEEMAGFEFQVIAEDS
GQPMLASSVSVWVSLLDANDNAPEVVQPVLSDGKASLSVLVNASTGHLLVPIETPNGLGP
AGTDTPPLATHSSRPFLLTTIVARDADSGANGEPLYSIRSGNEAHLFILNPHTGQLFVNV
TNASSLIGSEWELEIVVEDQGSPPLQTRALLRVMFVTSVDHLRDSARKPGALSMSMLTVI
CLAVLLGIFGLILALFMSICRTEKKDNRAYNCREAESTYRQQPKRPQKHIQKADIHLVPV
LRGQAGEPCEVGQSHKDVDKEAMMEAGWDPCLQAPFHLTPTLYRTLRNQGNQGAPAESRE
VLQDTVNLLFNHPRQRNASRENLNLPEPQPATGQPRSRPLKVAGSPTGRLAGDQGSEEAP
QRPPASSATLRRQRHLNGKVSPEKESGPRQILRSLVRLSVAAFAERNPVEELTVDSPPVQ
QISQLLSLLHQGQFQPKPNHRGNKYLAKPGGSRSAIPDTDGPSARAGGQTDPEQEEGPLD
PEEDLSVKQLLEEELSSLLDPSTGLALDRLSAPDPAWMARLSLPLTTNYRDNVISPDAAA
TEEPRTFQTFGKAEAPELSPTGTRLASTFVSEMSSLLEMLLEQRSSMPVEAASEALRRLS
VCGRTLSLDLATSAASGMKVQGDPGGKTGTEGKSRGSSSSSRCL
Function
Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions. Acts as a regulator of cell migration, probably via increasing cell-cell adhesion. Promotes homotypic calcium-dependent aggregation and adhesion and clusters at intercellular junctions. Unable to bind to catenins, weakly associates with the cytoskeleton.
Tissue Specificity
Expressed in highly vascularized tissues including the heart and placenta, but most tissues contain a low level of expression . Prominent expression in the spleen . Present in villous and extravillous trophoblast (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Diencephalic-mesencephalic junction dysplasia syndrome 1 DISACBMY Definitive Autosomal recessive [1]
Alcohol dependence DIS4ZSCO Strong Biomarker [2]
Cerebellar ataxia DIS9IRAV Strong Genetic Variation [3]
Epilepsy DISBB28L Strong Biomarker [3]
Isolated congenital microcephaly DISUXHZ6 Strong Biomarker [3]
Bipolar disorder DISAM7J2 moderate Genetic Variation [4]
Intellectual disability DISMBNXP moderate Biomarker [3]
Schizoaffective disorder DISLBW6B moderate Genetic Variation [4]
Schizophrenia DISSRV2N moderate Genetic Variation [4]
Diencephalic-mesencephalic junction dysplasia DIS91LZ2 Supportive Autosomal recessive [1]
Dystonia DISJLFGW Limited Genetic Variation [3]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Protocadherin-12 (PCDH12). [5]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protocadherin-12 (PCDH12). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Protocadherin-12 (PCDH12). [7]
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References

1 Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome. Ann Neurol. 2018 Nov;84(5):638-647. doi: 10.1002/ana.25327. Epub 2018 Oct 4.
2 Cadherins and neuropsychiatric disorders.Brain Res. 2012 Aug 27;1470:130-44. doi: 10.1016/j.brainres.2012.06.020. Epub 2012 Jul 2.
3 Homozygous PCDH12 variants result in phenotype of cerebellar ataxia, dystonia, retinopathy, and dysmorphism.J Hum Genet. 2019 Feb;64(2):183-189. doi: 10.1038/s10038-018-0541-9. Epub 2018 Nov 20.
4 Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.Transl Psychiatry. 2017 Oct 24;7(10):e1249. doi: 10.1038/tp.2017.210.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 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.
7 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.