Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5TUH02)

• DOT Name: Immunoglobulin superfamily member 6 (IGSF6)
• Synonyms: IgSF6; Protein DORA
• Gene Name: IGSF6
• Related Disease:
  Allergic contact dermatitis
  Hepatitis C virus infection
  Insomnia
  Sleep disorder
  Immune system disorder
  Crohn disease
• UniProt ID: IGSF6_HUMAN
• Pfam ID: PF07686
• Sequence:
  MGTASRSNIARHLQTNLILFCVGAVGACTLSVTQPWYLEVDYTHEAVTIKCTFSATGCPS
  EQPTCLWFRYGAHQPENLCLDGCKSEADKFTVREALKENQVSLTVNRVTSNDSAIYICGI
  AFPSVPEARAKQTGGGTTLVVREIKLLSKELRSFLTALVSLLSVYVTGVCVAFILLSKSK
  SNPLRNKEIKEDSQKKKSARRIFQEIAQELYHKRHVETNQQSEKDNNTYENRRVLSNYER
  P
• Tissue Specificity: Expressed in peripheral blood lymphocytes, spleen and lymph node, with low levels in thymus, bone marrow and fetal liver. No expression in non-immune tissues.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic contact dermatitis	DISFFVF9	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[2]
Insomnia	DIS0AFR7	Strong	Biomarker	[3]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[4]
Immune system disorder	DISAEGPH	moderate	Biomarker	[5]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Immunoglobulin superfamily member 6 (IGSF6).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Immunoglobulin superfamily member 6 (IGSF6).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Immunoglobulin superfamily member 6 (IGSF6).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Immunoglobulin superfamily member 6 (IGSF6).	[10]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Immunoglobulin superfamily member 6 (IGSF6).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Immunoglobulin superfamily member 6 (IGSF6).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Immunoglobulin superfamily member 6 (IGSF6).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Immunoglobulin superfamily member 6 (IGSF6).	[13]

References

• [1] Gene transcripts as potential diagnostic markers for allergic contact dermatitis.Contact Dermatitis. 2005 Aug;53(2):100-6. doi: 10.1111/j.0105-1873.2005.00658.x.
• [2] Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents With Chronic Hepatitis C Virus: Part 1 of the DORA Study.Hepatology. 2020 Feb;71(2):456-462. doi: 10.1002/hep.30840. Epub 2019 Aug 13.
• [3] The dual orexinergic receptor antagonist DORA-22 improves the sleep disruption and memory impairment produced by a rodent insomnia model.Sleep. 2020 Mar 12;43(3):zsz241. doi: 10.1093/sleep/zsz241.
• [4] PSPH-D-18-00526: Effect of a dual orexin receptor antagonist (DORA-12) on sleep and event-related oscillations in rats exposed to ethanol vapor during adolescence.Psychopharmacology (Berl). 2020 Oct;237(10):2917-2927. doi: 10.1007/s00213-019-05371-4. Epub 2019 Oct 28.
• [5] Genetic variation in the IGSF6 gene and lack of association with inflammatory bowel disease.Eur J Immunogenet. 2003 Jun;30(3):187-90. doi: 10.1046/j.1365-2370.2003.00387.x.
• [6] The mouse and human IGSF6 (DORA) genes map to the inflammatory bowel disease 1 locus and are embedded in an intron of a gene of unknown function.Immunogenetics. 2000 Nov;52(1-2):112-20. doi: 10.1007/s002510000259.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [10] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [11] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.