Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT45PVKC)

• DOT Name: Cell adhesion molecule 2 (CADM2)
• Synonyms: Immunoglobulin superfamily member 4D; IgSF4D; Nectin-like protein 3; NECL-3; Synaptic cell adhesion molecule 2; SynCAM 2
• Gene Name: CADM2
• Related Disease:
  Hyperglycemia
  Non-insulin dependent diabetes
  Advanced cancer
  Anxiety
  Autism
  Clear cell renal carcinoma
  Endometriosis
  Esophageal squamous cell carcinoma
  Glioma
  Hepatitis B virus infection
  Neoplasm
  Obesity
  Open-angle glaucoma
  Psoriasis
  Renal cell carcinoma
  Retinoblastoma
  Schizophrenia
  Acute myelogenous leukaemia
  Glaucoma/ocular hypertension
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Bipolar disorder
• UniProt ID: CADM2_HUMAN
• Pfam ID: PF08205 ; PF13927 ; PF07686
• Sequence:
  MIWKRSAVLRFYSVCGLLLQGSQGQFPLTQNVTVVEGGTAILTCRVDQNDNTSLQWSNPA
  QQTLYFDDKKALRDNRIELVRASWHELSISVSDVSLSDEGQYTCSLFTMPVKTSKAYLTV
  LGVPEKPQISGFSSPVMEGDLMQLTCKTSGSKPAADIRWFKNDKEIKDVKYLKEEDANRK
  TFTVSSTLDFRVDRSDDGVAVICRVDHESLNATPQVAMQVLEIHYTPSVKIIPSTPFPQE
  GQPLILTCESKGKPLPEPVLWTKDGGELPDPDRMVVSGRELNILFLNKTDNGTYRCEATN
  TIGQSSAEYVLIVHDVPNTLLPTTIIPSLTTATVTTTVAITTSPTTSATTSSIRDPNALA
  GQNGPDHALIGGIVAVVVFVTLCSIFLLGRYLARHKGTYLTNEAKGAEDAPDADTAIINA
  EGSQVNAEEKKEYFI
• Function: Adhesion molecule that engages in homo- and heterophilic interactions with the other nectin-like family members, leading to cell aggregation. Important for synapse organization, providing regulated trans-synaptic adhesion. Preferentially binds to oligodendrocytes.
• Reactome Pathway: Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Anxiety	DISIJDBA	Strong	Genetic Variation	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[6]
Endometriosis	DISX1AG8	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Glioma	DIS5RPEH	Strong	Altered Expression	[9]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Obesity	DIS47Y1K	Strong	Genetic Variation	[12]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[13]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[15]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[16]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[17]
Glaucoma/ocular hypertension	DISLBXBY	moderate	Genetic Variation	[18]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[11]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Biomarker	[11]
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[19]

6 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 Cell adhesion molecule 2 (CADM2).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cell adhesion molecule 2 (CADM2).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell adhesion molecule 2 (CADM2).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cell adhesion molecule 2 (CADM2).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cell adhesion molecule 2 (CADM2).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cell adhesion molecule 2 (CADM2).	[23]

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 Cell adhesion molecule 2 (CADM2).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cell adhesion molecule 2 (CADM2).	[26]

References

• [1] Cadm2 regulates body weight and energy homeostasis in mice.Mol Metab. 2018 Feb;8:180-188. doi: 10.1016/j.molmet.2017.11.010. Epub 2017 Nov 22.
• [2] Exploring single nucleotide polymorphisms previously related to obesity and metabolic traits in pediatric-onset type 2 diabetes.Acta Diabetol. 2017 Jul;54(7):653-662. doi: 10.1007/s00592-017-0987-9. Epub 2017 Apr 12.
• [3] Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression.Biochem Biophys Res Commun. 2013 Jun 14;435(4):526-32. doi: 10.1016/j.bbrc.2013.04.074. Epub 2013 May 3.
• [4] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [5] Modeling prior information of common genetic variants improves gene discovery for neuroticism.Hum Mol Genet. 2017 Nov 15;26(22):4530-4539. doi: 10.1093/hmg/ddx340.
• [6] Hypoxia-Regulated miR-146a Targets Cell Adhesion Molecule 2 to Promote Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma.Cell Physiol Biochem. 2018;49(3):920-931. doi: 10.1159/000493224. Epub 2018 Sep 5.
• [7] Identification of endometriosis-related genes by representational difference analysis of cDNA.Aust N Z J Obstet Gynaecol. 2012 Apr;52(2):140-5. doi: 10.1111/j.1479-828X.2011.01405.x. Epub 2012 Jan 25.
• [8] The CADM2/Akt pathway is involved in the inhibitory effect of miR-21-5p downregulation on proliferation and apoptosis in esophageal squamous cell carcinoma cells.Chem Biol Interact. 2018 May 25;288:76-82. doi: 10.1016/j.cbi.2018.04.021. Epub 2018 Apr 19.
• [9] CADM2 inhibits human glioma proliferation, migration and invasion.Oncol Rep. 2019 Apr;41(4):2273-2280. doi: 10.3892/or.2019.7010. Epub 2019 Feb 13.
• [10] Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy.J Cancer Res Clin Oncol. 2014 Jan;140(1):109-16. doi: 10.1007/s00432-013-1536-8. Epub 2013 Nov 17.
• [11] CADM2, as a new target of miR-10b, promotes tumor metastasis through FAK/AKT pathway in hepatocellular carcinoma.J Exp Clin Cancer Res. 2018 Mar 5;37(1):46. doi: 10.1186/s13046-018-0699-1.
• [12] Genetic variation in CADM2 as a link between psychological traits and obesity.Sci Rep. 2019 May 14;9(1):7339. doi: 10.1038/s41598-019-43861-9.
• [13] A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nat Commun. 2018 Jun 11;9(1):2278. doi: 10.1038/s41467-018-04555-4.
• [14] A novel splicing variant of CADM2 as a protective transcript of psoriasis.Biochem Biophys Res Commun. 2011 Sep 9;412(4):626-32. doi: 10.1016/j.bbrc.2011.08.013. Epub 2011 Aug 11.
• [15] Downregulation of microRNA?82 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation.Int J Oncol. 2018 Dec;53(6):2615-2626. doi: 10.3892/ijo.2018.4587. Epub 2018 Oct 9.
• [16] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [17] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [18] Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.Nat Genet. 2018 Sep;50(9):1335-1341. doi: 10.1038/s41588-018-0184-y. Epub 2018 Aug 13.
• [19] Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
• [20] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] BET bromodomain protein inhibition is a therapeutic option for medulloblastoma. Oncotarget. 2013 Nov;4(11):2080-95.
• [26] 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.