Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQEG2X1)

• DOT Name: Immunoglobulin superfamily member 11 (IGSF11)
• Synonyms: IgSF11; Brain and testis-specific immunoglobulin superfamily protein; Bt-IGSF; V-set and immunoglobulin domain-containing protein 3
• Gene Name: IGSF11
• Related Disease:
  Advanced cancer
  Gastric cancer
  Gastric neoplasm
  Hepatocellular carcinoma
  Schizophrenia
  Stomach cancer
• UniProt ID: IGS11_HUMAN
• Pfam ID: PF13927 ; PF07686
• Sequence:
  MTSQRSPLAPLLLLSLHGVAASLEVSESPGSIQVARGQPAVLPCTFTTSAALINLNVIWM
  VTPLSNANQPEQVILYQGGQMFDGAPRFHGRVGFTGTMPATNVSIFINNTQLSDTGTYQC
  LVNNLPDIGGRNIGVTGLTVLVPPSAPHCQIQGSQDIGSDVILLCSSEEGIPRPTYLWEK
  LDNTLKLPPTATQDQVQGTVTIRNISALSSGLYQCVASNAIGTSTCLLDLQVISPQPRNI
  GLIAGAIGTGAVIIIFCIALILGAFFYWRSKNKEEEEEEIPNEIREDDLPPKCSSAKAFH
  TEISSSDNNTLTSSNAYNSRYWSNNPKVHRNTESVSHFSDLGQSFSFHSGNANIPSIYAN
  GTHLVPGQHKTLVVTANRGSSPQVMSRSNGSVSRKPRPPHTHSYTISHATLERIGAVPVM
  VPAQSRAGSLV
• Function: Functions as a cell adhesion molecule through homophilic interaction. Stimulates cell growth.
• Tissue Specificity: Abundantly expressed in testis and ovary and to a lower extent in brain, kidney and skeletal muscle.
• KEGG Pathway: Cell adhesion molecules (hsa04514)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]

4 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 Immunoglobulin superfamily member 11 (IGSF11).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Immunoglobulin superfamily member 11 (IGSF11).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Immunoglobulin superfamily member 11 (IGSF11).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Immunoglobulin superfamily member 11 (IGSF11).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Immunoglobulin superfamily member 11 (IGSF11).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Immunoglobulin superfamily member 11 (IGSF11).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Immunoglobulin superfamily member 11 (IGSF11).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Immunoglobulin superfamily member 11 (IGSF11).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Immunoglobulin superfamily member 11 (IGSF11).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Immunoglobulin superfamily member 11 (IGSF11).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Immunoglobulin superfamily member 11 (IGSF11).	[14]

References

• [1] Construction of a versatile expression library for all human single-pass transmembrane proteins for receptor pairings by high throughput screening.J Biotechnol. 2017 Oct 20;260:18-30. doi: 10.1016/j.jbiotec.2017.08.023. Epub 2017 Sep 1.
• [2] IGSF11 gene, frequently up-regulated in intestinal-type gastric cancer, encodes adhesion molecule homologous to CXADR, FLJ22415 and ESAM.Int J Oncol. 2003 Aug;23(2):525-31.
• [3] Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas.Cancer Sci. 2005 Aug;96(8):498-506. doi: 10.1111/j.1349-7006.2005.00073.x.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.