Details of Drug Off-Target (DOT)

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

• DOT Name: Immunoglobulin superfamily member 21 (IGSF21)
• Synonyms: IgSF21
• Gene Name: IGSF21
• Related Disease:
  Diabetic retinopathy
  Non-insulin dependent diabetes
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Pancreatic cancer
  Acute myelogenous leukaemia
• UniProt ID: IGS21_HUMAN
• Pfam ID: PF07686
• Sequence:
  MRTAPSLRRCVCLLLAAILDLARGYLTVNIEPLPPVVAGDAVTLKCNFKTDGRMREIVWY
  RVTDGGTIKQKIFTFDAMFSTNYSHMENYRKREDLVYQSTVRLPEVRISDNGPYECHVGI
  YDRATREKVVLASGNIFLNVMAPPTSIEVVAADTPAPFSRYQAQNFTLVCIVSGGKPAPM
  VYFKRDGEPIDAVPLSEPPAASSGPLQDSRPFRSLLHRDLDDTKMQKSLSLLDAENRGGR
  PYTERPSRGLTPDPNILLQPTTENIPETVVSREFPRWVHSAEPTYFLRHSRTPSSDGTVE
  VRALLTWTLNPQIDNEALFSCEVKHPALSMPMQAEVTLVAPKGPKIVMTPSRARVGDTVR
  ILVHGFQNEVFPEPMFTWTRVGSRLLDGSAEFDGKELVLERVPAELNGSMYRCTAQNPLG
  STDTHTRLIVFENPNIPRGTEDSNGSIGPTGARLTLVLALTVILELT
• Function: Involved in synaptic inhibition in the brain. Selectively regulates inhibitory presynaptic differentiation through interacting with presynaptic NRXN2.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Immunoglobulin superfamily member 21 (IGSF21).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Immunoglobulin superfamily member 21 (IGSF21).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Immunoglobulin superfamily member 21 (IGSF21).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Immunoglobulin superfamily member 21 (IGSF21).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Immunoglobulin superfamily member 21 (IGSF21).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Immunoglobulin superfamily member 21 (IGSF21).	[10]

References

• [1] Association between LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms and diabetic retinopathy of type 2 diabetes mellitus in the Chinese Han population.J Gene Med. 2016 Oct;18(10):282-287. doi: 10.1002/jgm.2926.
• [2] Altered genome-wide methylation in endometriosis.Reprod Sci. 2014 Oct;21(10):1237-43. doi: 10.1177/1933719114532841. Epub 2014 Apr 30.
• [3] Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer. Chem Res Toxicol. 2015 Jun 15;28(6):1144-55. doi: 10.1021/tx500393y. Epub 2015 Jun 3.
• [4] Genetic polymorphisms associated with pancreatic cancer survival: a genome-wide association study.Int J Cancer. 2017 Aug 15;141(4):678-686. doi: 10.1002/ijc.30762. Epub 2017 May 15.
• [5] 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.
• [6] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer. Chem Res Toxicol. 2015 Jun 15;28(6):1144-55. doi: 10.1021/tx500393y. Epub 2015 Jun 3.
• [9] 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.
• [10] 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.
• [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.