Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQK8XLK)

• DOT Name: Immunoglobulin-like domain-containing receptor 1 (ILDR1)
• Synonyms: Angulin-2
• Gene Name: ILDR1
• Related Disease:
  Nonsyndromic genetic hearing loss
  Autosomal recessive nonsyndromic hearing loss 42
  B-cell lymphoma
  Deafness
  Myelodysplastic syndrome
  Sensorineural hearing loss disorder
  Hearing loss, autosomal recessive
  Asthma
• UniProt ID: ILDR1_HUMAN
• Pfam ID: PF05624
• Sequence:
  MAWPKLPAPWLLLCTWLPAGCLSLLVTVQHTERYVTLFASIILKCDYTTSAQLQDVVVTW
  RFKSFCKDPIFDYYSASYQAALSLGQDPSNDCNDNQREVRIVAQRRGQNEPVLGVDYRQR
  KITIQNRADLVINEVMWWDHGVYYCTIEAPGDTSGDPDKEVKLIVLHWLTVIFIILGALL
  LLLLIGVCWCQCCPQYCCCYIRCPCCPAHCCCPEEALARHRYMKQAQALGPQMMGKPLYW
  GADRSSQVSSYPMHPLLQRDLSLPSSLPQMPMTQTTNQPPIANGVLEYLEKELRNLNLAQ
  PLPPDLKGRFGHPCSMLSSLGSEVVERRIIHLPPLIRDLSSSRRTSDSLHQQWLTPIPSR
  PWDLREGRSHHHYPDFHQELQDRGPKSWALERRELDPSWSGRHRSSRLNGSPIHWSDRDS
  LSDVPSSSEARWRPSHPPFRSRCQERPRRPSPRESTQRHGRRRRHRSYSPPLPSGLSSWS
  SEEDKERQPQSWRAHRRGSHSPHWPEEKPPSYRSLDITPGKNSRKKGSVERRSEKDSSHS
  GRSVVI
• Function: Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (tTJs). Crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs. Mediates fatty acids and lipoproteins-stimulated CCK/cholecystokinin secretion in the small intestine. In the inner ear, may regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1; (Microbial infection) Promotes influenza virus infection by inhibiting viral nucleoprotein NP binding to PLSCR1 and thereby PLSCR1-mediated antiviral activity.
• Tissue Specificity: Mainly expressed in prostate and to a lower extent in testis, pancreas, kidney, heart and liver.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nonsyndromic genetic hearing loss	DISZX61P	Definitive	Autosomal recessive	[1]
Autosomal recessive nonsyndromic hearing loss 42	DIS9TEL3	Strong	Autosomal recessive	[2]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[3]
Deafness	DISKCLH4	Strong	Biomarker	[4]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[5]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[6]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[7]
Asthma	DISW9QNS	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Immunoglobulin-like domain-containing receptor 1 (ILDR1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Immunoglobulin-like domain-containing receptor 1 (ILDR1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Immunoglobulin-like domain-containing receptor 1 (ILDR1).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Immunoglobulin-like domain-containing receptor 1 (ILDR1).	[13]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Immunoglobulin-like domain-containing receptor 1 (ILDR1).	[14]

1 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 decreases the methylation of Immunoglobulin-like domain-containing receptor 1 (ILDR1).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42. Am J Hum Genet. 2011 Feb 11;88(2):127-37. doi: 10.1016/j.ajhg.2010.12.011. Epub 2011 Jan 20.
• [3] Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways.Hum Mol Genet. 2020 Jan 1;29(1):70-79. doi: 10.1093/hmg/ddz228.
• [4] Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment.Sci Rep. 2019 Oct 23;9(1):15192. doi: 10.1038/s41598-019-51630-x.
• [5] A new recurrent chromosomal translocation t(3;11)(q13;q14) in myelodysplastic syndromes associated with overexpression of the ILDR1 gene.Leuk Res. 2012 Jul;36(7):852-6. doi: 10.1016/j.leukres.2012.01.026. Epub 2012 Feb 25.
• [6] Downsloping high-frequency hearing loss due to inner ear tricellular tight junction disruption by a novel ILDR1 mutation in the Ig-like domain.PLoS One. 2015 Feb 10;10(2):e0116931. doi: 10.1371/journal.pone.0116931. eCollection 2015.
• [7] [Gene therapy for human hearing loss: challenges and promises]. Med Sci (Paris). 2013 Oct;29(10):883-9. doi: 10.1051/medsci/20132910016. Epub 2013 Oct 18.
• [8] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [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] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Genomic and phenotypic alterations of the neuronal-like cells derived from human embryonal carcinoma stem cells (NT2) caused by exposure to organophosphorus compounds paraoxon and mipafox. Int J Mol Sci. 2014 Jan 9;15(1):905-26. doi: 10.3390/ijms15010905.