Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWU5FLZ)

• DOT Name: Contactin-5 (CNTN5)
• Synonyms: Neural recognition molecule NB-2; hNB-2
• Gene Name: CNTN5
• Related Disease:
  Atrial fibrillation
  Autism spectrum disorder
  Autosomal recessive juvenile Parkinson disease 2
  Behcet disease
  Cardiac failure
  Congestive heart failure
  Differentiated thyroid carcinoma
  High blood pressure
  Major depressive disorder
  Neurodevelopmental disorder
  Obesity
  Primary biliary cholangitis
  Anorexia nervosa cachexia
  Attention deficit hyperactivity disorder
  Bipolar disorder
  Intellectual disability
  Schizophrenia
  Gout
• UniProt ID: CNTN5_HUMAN
• PDB ID: 4N68; 5E52
• Pfam ID: PF00041 ; PF07679 ; PF13927
• Sequence:
  MASSWKLMLFLSVTMCLSEYSKSLPGLSTSYAALLRIKKSSSSSLFGSKTRPRYSSPSLG
  TLSASSPSWLGAAQNYYSPINLYHSSDAFKQDESVDYGPVFVQEPDDIIFPTDSDEKKVA
  LNCEVRGNPVPSYRWLRNGTEIDLESDYRYSLIDGTFIISNPSEAKDSGHYQCLATNTVG
  SILSREATLQFAYLGNFSGRTRSAVSVREGQGVVLMCSPPPHSPEIIYSWVFNEFPSFVA
  EDSRRFISQETGNLYISKVQTSDVGSYICLVKNTVTNARVLSPPTPLTLRNDGVMGEYEP
  KIEVHFPFTVTAAKGTTVKMECFALGNPVPTITWMKVNGYIPSKARLRKSQAVLEIPNVQ
  LDDAGIYECRAENSRGKNSFRGQLQVYTYPHWVEKLNDTQLDSGSPLRWECKATGKPRPT
  YRWLKNGVPLSPQSRVEMVNGVLMIHNVNQSDAGMYQCLAENKYGAIYASAELKILASAP
  TFALNQLKKTIIVTKDQEVVIECKPQGSPKPTISWKKGDRAVRENKRIAILPDGSLRILN
  ASKSDEGKYVCRGENVFGSAEIIASLSVKEPTRIELTPKRTELTVGESIVLNCKAIHDAS
  LDVTFYWTLKGQPIDFEEEGGHFESIRAQASSADLMIRNILLMHAGRYGCRVQTTADSVS
  DEAELLVRGPPGPPGIVIVEEITESTATLSWSPAADNHSPISSYNLQARSPFSLGWQTVK
  TVPEIITGDMESAMAVDLNPWVEYEFRVVATNPIGTGDPSTPSRMIRTNEAVPKTAPTNV
  SGRSGRRHELVIAWEPVSEEFQNGEGFGYIVAFRPNGTRGWKEKMVTSSEASKFIYRDES
  VPPLTPFEVKVGVYNNKGDGPFSQIVVICSAEGEPSAAPTDVKATSVSVSEILVAWKHIK
  ESLGRPQGFEVGYWKDMEQEDTAETVKTRGNESFVILTGLEGNTLYHFTVRAYNGAGYGP
  PSSEVSATTKKSPPSQAPSNLRWEQQGSQVSLGWEPVIPLANESEVVGYKVFYRQEGHSN
  SQVIETQKLQAVVPLPDAGVYIIEVRAYSEGGDGTASSQIRVPSYSGGKITSAQSTLHSL
  STSSSSVTLLLALMIPSTSW
• Function: Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity in the cerebral cortical neurons but not in hippocampal neurons. Probably involved in neuronal activity in the auditory system.
• Tissue Specificity: Expressed in brain and kidney and at very low level in placenta. Not expressed in other tissues. In brain, it is highly expressed in the occipital lobe, amygdala, cerebral cortex, frontal lobe, thalamus and temporal lobe. Expressed at moderate level in the cerebellum, substantia nigra, putamen, medulla and hippocampus. Weakly expressed in the spinal cord and caudate nucleus. Weakly or not expressed in the corpus callosum.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Autosomal recessive juvenile Parkinson disease 2	DISNSTD1	Strong	Biomarker	[3]
Behcet disease	DISSYMBS	Strong	Genetic Variation	[4]
Cardiac failure	DISDC067	Strong	Genetic Variation	[1]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[1]
Differentiated thyroid carcinoma	DIS1V20Y	Strong	Biomarker	[5]
High blood pressure	DISY2OHH	Strong	Biomarker	[6]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[7]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[6]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[8]
Anorexia nervosa cachexia	DISFO5RQ	moderate	Biomarker	[9]
Attention deficit hyperactivity disorder	DISL8MX9	moderate	Biomarker	[9]
Bipolar disorder	DISAM7J2	moderate	Biomarker	[9]
Intellectual disability	DISMBNXP	moderate	Biomarker	[9]
Schizophrenia	DISSRV2N	moderate	Biomarker	[9]
Gout	DISHC0U7	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Contactin-5 (CNTN5).	[11]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Contactin-5 (CNTN5).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Contactin-5 (CNTN5).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Contactin-5 (CNTN5).	[15]

1 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 increases the methylation of Contactin-5 (CNTN5).	[13]

References

• [1] Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes.BMC Med Genet. 2007 Sep 19;8 Suppl 1(Suppl 1):S5. doi: 10.1186/1471-2350-8-S1-S5.
• [2] Structural abnormalities in the primary somatosensory cortex and a normal behavioral profile in Contactin-5 deficient mice.Cell Adh Migr. 2018 Jan 2;12(1):5-18. doi: 10.1080/19336918.2017.1288788. Epub 2017 Mar 27.
• [3] Discovery of a frameshift mutation in podocalyxin-like (PODXL) gene, coding for a neural adhesion molecule, as causal for autosomal-recessive juvenile Parkinsonism. J Med Genet. 2016 Jul;53(7):450-6. doi: 10.1136/jmedgenet-2015-103459. Epub 2016 Feb 10.
• [4] Genetic Analysis with the Immunochip Platform in Behet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci.PLoS One. 2016 Aug 22;11(8):e0161305. doi: 10.1371/journal.pone.0161305. eCollection 2016.
• [5] The influence of neural cell adhesion molecule isoform 140 on the metastasis of thyroid carcinoma.Clin Exp Metastasis. 2013 Mar;30(3):299-307. doi: 10.1007/s10585-012-9537-6. Epub 2012 Sep 27.
• [6] Unexpected phenotypic effects of a transgene integration causing a knockout of the endogenous Contactin-5 gene in mice.Transgenic Res. 2018 Feb;27(1):1-13. doi: 10.1007/s11248-017-0053-y. Epub 2017 Dec 20.
• [7] Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics.Transl Psychiatry. 2018 Jan 10;8(1):10. doi: 10.1038/s41398-017-0056-8.
• [8] Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.Am J Hum Genet. 2012 Oct 5;91(4):721-8. doi: 10.1016/j.ajhg.2012.08.010. Epub 2012 Sep 20.
• [9] A current view on contactin-4, -5, and -6: Implications in neurodevelopmental disorders.Mol Cell Neurosci. 2017 Jun;81:72-83. doi: 10.1016/j.mcn.2016.12.004. Epub 2017 Jan 5.
• [10] Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout.Ann Rheum Dis. 2019 Oct;78(10):1430-1437. doi: 10.1136/annrheumdis-2019-215521. Epub 2019 Jul 8.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [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] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.