Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8LBJN8)

• DOT Name: Neural cell adhesion molecule 2 (NCAM2)
• Synonyms: N-CAM-2; NCAM-2
• Gene Name: NCAM2
• Related Disease:
  Alzheimer disease
  Autism
  Autism spectrum disorder
  Brain disease
  Breast cancer
  Breast carcinoma
  Hepatitis C virus infection
  Megalencephaly
  Obesity
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Endometrial carcinoma
  Neurodevelopmental disorder
  Intellectual disability
• UniProt ID: NCAM2_HUMAN
• PDB ID: 2DOC; 2JLL; 2KBG; 2V5T; 2VAJ; 2WIM; 2XY1; 2XY2; 2XYC
• Pfam ID: PF00041 ; PF07679 ; PF13927
• Sequence:
  MSLLLSFYLLGLLVSSGQALLQVTISLSKVELSVGESKFFTCTAIGEPESIDWYNPQGEK
  IISTQRVVVQKEGVRSRLTIYNANIEDAGIYRCQATDAKGQTQEATVVLEIYQKLTFREV
  VSPQEFKQGEDAEVVCRVSSSPAPAVSWLYHNEEVTTISDNRFAMLANNNLQILNINKSD
  EGIYRCEGRVEARGEIDFRDIIVIVNVPPAISMPQKSFNATAERGEEMTFSCRASGSPEP
  AISWFRNGKLIEENEKYILKGSNTELTVRNIINSDGGPYVCRATNKAGEDEKQAFLQVFV
  QPHIIQLKNETTYENGQVTLVCDAEGEPIPEITWKRAVDGFTFTEGDKSLDGRIEVKGQH
  GSSSLHIKDVKLSDSGRYDCEAASRIGGHQKSMYLDIEYAPKFISNQTIYYSWEGNPINI
  SCDVKSNPPASIHWRRDKLVLPAKNTTNLKTYSTGRKMILEIAPTSDNDFGRYNCTATNH
  IGTRFQEYILALADVPSSPYGVKIIELSQTTAKVSFNKPDSHGGVPIHHYQVDVKEVASE
  IWKIVRSHGVQTMVVLNNLEPNTTYEIRVAAVNGKGQGDYSKIEIFQTLPVREPSPPSIH
  GQPSSGKSFKLSITKQDDGGAPILEYIVKYRSKDKEDQWLEKKVQGNKDHIILEHLQWTM
  GYEVQITAANRLGYSEPTVYEFSMPPKPNIIKDTLFNGLGLGAVIGLGVAALLLILVVTD
  VSCFFIRQCGLLMCITRRMCGKKSGSSGKSKELEEGKAAYLKDGSKEPIVEMRTEDERVT
  NHEDGSPVNEPNETTPLTEPEKLPLKEEDGKEALNPETIEIKVSNDIIQSKEDDSKA
• Function: May play important roles in selective fasciculation and zone-to-zone projection of the primary olfactory axons.
• Tissue Specificity: Expressed most strongly in adult and fetal brain.
• KEGG Pathway:
  Virion - Ebolavirus and Lyssavirus (hsa03265)
  Cell adhesion molecules (hsa04514)
  Prion disease (hsa05020)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Brain disease	DIS6ZC3X	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[5]
Megalencephaly	DISYW5SV	Strong	Genetic Variation	[2]
Obesity	DIS47Y1K	Strong	Genetic Variation	[6]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[7]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[8]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[8]
Endometrial carcinoma	DISXR5CY	moderate	Genetic Variation	[9]
Neurodevelopmental disorder	DIS372XH	moderate	Genetic Variation	[10]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neural cell adhesion molecule 2 (NCAM2).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neural cell adhesion molecule 2 (NCAM2).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Neural cell adhesion molecule 2 (NCAM2).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neural cell adhesion molecule 2 (NCAM2).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neural cell adhesion molecule 2 (NCAM2).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Neural cell adhesion molecule 2 (NCAM2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neural cell adhesion molecule 2 (NCAM2).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Neural cell adhesion molecule 2 (NCAM2).	[21]

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 increases the methylation of Neural cell adhesion molecule 2 (NCAM2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Neural cell adhesion molecule 2 (NCAM2).	[20]

References

• [1] A-dependent reduction of NCAM2-mediated synaptic adhesion contributes to synapse loss in Alzheimer's disease.Nat Commun. 2015 Nov 27;6:8836. doi: 10.1038/ncomms9836.
• [2] NCAM2 deletion in a boy with macrocephaly and autism: Cause, association or predisposition?.Eur J Med Genet. 2016 Oct;59(10):493-8. doi: 10.1016/j.ejmg.2016.08.006. Epub 2016 Sep 2.
• [3] Neural Cell Adhesion Molecule 2 (NCAM2)-Induced c-Src-Dependent Propagation of Submembrane Ca2+ Spikes Along Dendrites Inhibits Synapse Maturation.Cereb Cortex. 2019 Apr 1;29(4):1439-1459. doi: 10.1093/cercor/bhy041.
• [4] Neural cell adhesion molecule 2 as a target molecule for prostate and breast cancer gene therapy.Cancer Sci. 2011 Apr;102(4):808-14. doi: 10.1111/j.1349-7006.2011.01855.x. Epub 2011 Feb 25.
• [5] Impact of IFNL4 Genetic Variants on Sustained Virologic Response and Viremia in Hepatitis C Virus Genotype 3 Patients.J Interferon Cytokine Res. 2019 Oct;39(10):642-649. doi: 10.1089/jir.2019.0013. Epub 2019 Jul 1.
• [6] A genome-wide association study on obesity and obesity-related traits.PLoS One. 2011 Apr 28;6(4):e18939. doi: 10.1371/journal.pone.0018939.
• [7] Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecol Oncol. 2019 May;153(2):343-355. doi: 10.1016/j.ygyno.2019.02.023. Epub 2019 Mar 19.
• [8] Novel biomarkers for prostate cancer including noncoding transcripts.Am J Pathol. 2009 Dec;175(6):2264-76. doi: 10.2353/ajpath.2009.080868. Epub 2009 Nov 5.
• [9] Identification of nine new susceptibility loci for endometrial cancer.Nat Commun. 2018 Aug 9;9(1):3166. doi: 10.1038/s41467-018-05427-7.
• [10] 21q21 deletion involving NCAM2: report of 3 cases with neurodevelopmental disorders.Eur J Med Genet. 2015 Jan;58(1):44-6. doi: 10.1016/j.ejmg.2014.11.004. Epub 2014 Nov 20.
• [11] Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders.Am J Med Genet A. 2016 Sep;170(9):2310-21. doi: 10.1002/ajmg.a.37831. Epub 2016 Jul 4.
• [12] 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.
• [13] 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.
• [14] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [15] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [16] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.