Details of Drug Off-Target (DOT)

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

• DOT Name: Cell adhesion molecule 3 (CADM3)
• Synonyms: Brain immunoglobulin receptor; Immunoglobulin superfamily member 4B; IgSF4B; Nectin-like protein 1; NECL-1; Synaptic cell adhesion molecule 3; SynCAM3; TSLC1-like protein 1; TSLL1
• Gene Name: CADM3
• Related Disease:
  Neoplasm
  Arthritis
  Charcot-Marie-Tooth disease, axonal, type 2FF
  Glioma
  Retinoblastoma
  Schizophrenia
• UniProt ID: CADM3_HUMAN
• PDB ID: 1Z9M
• Pfam ID: PF08205 ; PF13927 ; PF07686
• Sequence:
  MGAPAASLLLLLLLFACCWAPGGANLSQDDSQPWTSDETVVAGGTVVLKCQVKDHEDSSL
  QWSNPAQQTLYFGEKRALRDNRIQLVTSTPHELSISISNVALADEGEYTCSIFTMPVRTA
  KSLVTVLGIPQKPIITGYKSSLREKDTATLNCQSSGSKPAARLTWRKGDQELHGEPTRIQ
  EDPNGKTFTVSSSVTFQVTREDDGASIVCSVNHESLKGADRSTSQRIEVLYTPTAMIRPD
  PPHPREGQKLLLHCEGRGNPVPQQYLWEKEGSVPPLKMTQESALIFPFLNKSDSGTYGCT
  ATSNMGSYKAYYTLNVNDPSPVPSSSSTYHAIIGGIVAFIVFLLLIMLIFLGHYLIRHKG
  TYLTHEAKGSDDAPDADTAIINAEGGQSGGDDKKEYFI
• Function: Involved in the cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. Interaction with EPB41L1 may regulate structure or function of cell-cell junctions.
• Tissue Specificity: Isoform 1 is expressed mainly in adult and fetal brain. Isoform 2 is highly expressed in adult brain and weakly expressed in placenta. In brain, Isoform 2 is highly expressed in cerebellum.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway:
  Nectin/Necl trans heterodimerization (R-HSA-420597)
  Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Arthritis	DIST1YEL	Strong	Biomarker	[2]
Charcot-Marie-Tooth disease, axonal, type 2FF	DISP2EEU	Strong	Autosomal dominant	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[4]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[5]

5 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 3 (CADM3).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cell adhesion molecule 3 (CADM3).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cell adhesion molecule 3 (CADM3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cell adhesion molecule 3 (CADM3).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cell adhesion molecule 3 (CADM3).	[12]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cell adhesion molecule 3 (CADM3).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cell adhesion molecule 3 (CADM3).	[10]

References

• [1] Loss of NECL1, a novel tumor suppressor, can be restored in glioma by HDAC inhibitor-Trichostatin A through Sp1 binding site.Glia. 2009 Jul;57(9):989-99. doi: 10.1002/glia.20823.
• [2] Mass spectrometry-based analysis of cerebrospinal fluid from arthritis patients-immune-related candidate proteins affected by TNF blocking treatment.Arthritis Res Ther. 2019 Feb 15;21(1):60. doi: 10.1186/s13075-019-1846-6.
• [3] A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement. Brain. 2021 May 7;144(4):1197-1213. doi: 10.1093/brain/awab019.
• [4] miR-140-5p suppresses retinoblastoma cell proliferation, migration, and invasion by targeting CEMIP and CADM3.Cell Mol Biol (Noisy-le-grand). 2018 May 15;64(6):42-47.
• [5] 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.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] 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.
• [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.
• [12] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.