Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQG9W7C)

• DOT Name: Contactin-2 (CNTN2)
• Synonyms: Axonal glycoprotein TAG-1; Axonin-1; Transient axonal glycoprotein 1; TAX-1
• Gene Name: CNTN2
• Related Disease:
  Complex neurodevelopmental disorder
  Epilepsy, familial adult myoclonic, 5
  Benign adult familial myoclonic epilepsy
• UniProt ID: CNTN2_HUMAN
• PDB ID: 2OM5; 8K53
• Pfam ID: PF00041 ; PF07679 ; PF13927
• Sequence:
  MGTATRRKPHLLLVAAVALVSSSAWSSALGSQTTFGPVFEDQPLSVLFPEESTEEQVLLA
  CRARASPPATYRWKMNGTEMKLEPGSRHQLVGGNLVIMNPTKAQDAGVYQCLASNPVGTV
  VSREAILRFGFLQEFSKEERDPVKAHEGWGVMLPCNPPAHYPGLSYRWLLNEFPNFIPTD
  GRHFVSQTTGNLYIARTNASDLGNYSCLATSHMDFSTKSVFSKFAQLNLAAEDTRLFAPS
  IKARFPAETYALVGQQVTLECFAFGNPVPRIKWRKVDGSLSPQWTTAEPTLQIPSVSFED
  EGTYECEAENSKGRDTVQGRIIVQAQPEWLKVISDTEADIGSNLRWGCAAAGKPRPTVRW
  LRNGEPLASQNRVEVLAGDLRFSKLSLEDSGMYQCVAENKHGTIYASAELAVQALAPDFR
  LNPVRRLIPAARGGEILIPCQPRAAPKAVVLWSKGTEILVNSSRVTVTPDGTLIIRNISR
  SDEGKYTCFAENFMGKANSTGILSVRDATKITLAPSSADINLGDNLTLQCHASHDPTMDL
  TFTWTLDDFPIDFDKPGGHYRRTNVKETIGDLTILNAQLRHGGKYTCMAQTVVDSASKEA
  TVLVRGPPGPPGGVVVRDIGDTTIQLSWSRGFDNHSPIAKYTLQARTPPAGKWKQVRTNP
  ANIEGNAETAQVLGLTPWMDYEFRVIASNILGTGEPSGPSSKIRTREAAPSVAPSGLSGG
  GGAPGELIVNWTPMSREYQNGDGFGYLLSFRRQGSTHWQTARVPGADAQYFVYSNESVRP
  YTPFEVKIRSYNRRGDGPESLTALVYSAEEEPRVAPTKVWAKGVSSSEMNVTWEPVQQDM
  NGILLGYEIRYWKAGDKEAAADRVRTAGLDTSARVSGLHPNTKYHVTVRAYNRAGTGPAS
  PSANATTMKPPPRRPPGNISWTFSSSSLSIKWDPVVPFRNESAVTGYKMLYQNDLHLTPT
  LHLTGKNWIEIPVPEDIGHALVQIRTTGPGGDGIPAEVHIVRNGGTSMMVENMAVRPAPH
  PGTVISHSVAMLILIGSLEL
• Function: In conjunction with another transmembrane protein, CNTNAP2, contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region. May be involved in cell adhesion.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway:
  NCAM1 interactions (R-HSA-419037)
  NrCAM interactions (R-HSA-447038)
  L1CAM interactions (R-HSA-373760)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Definitive	Autosomal recessive	[1]
Epilepsy, familial adult myoclonic, 5	DISVW3BL	Strong	Autosomal recessive	[2]
Benign adult familial myoclonic epilepsy	DISIMWOV	Supportive	Autosomal dominant	[3]

2 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 Contactin-2 (CNTN2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Contactin-2 (CNTN2).	[10]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Contactin-2 (CNTN2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Contactin-2 (CNTN2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Contactin-2 (CNTN2).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Contactin-2 (CNTN2).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Contactin-2 (CNTN2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Contactin-2 (CNTN2).	[11]

References

• [1] 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.
• [2] TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus. Biochem Biophys Res Commun. 2001 Feb 16;281(1):220-6. doi: 10.1006/bbrc.2001.4334.
• [3] Autosomal recessive cortical myoclonic tremor and epilepsy: association with a mutation in the potassium channel associated gene CNTN2. Brain. 2013 Apr;136(Pt 4):1155-60. doi: 10.1093/brain/awt068. Epub 2013 Mar 21.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Treatment of ovarian cancer cell lines with 5-aza-2'-deoxycytidine upregulates the expression of cancer-testis antigens and class I major histocompatibility complex-encoded molecules. Cancer Immunol Immunother. 2009 Apr;58(4):589-601. doi: 10.1007/s00262-008-0582-6. Epub 2008 Sep 13.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] 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.
• [11] 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.