Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQR4RRB)

• DOT Name: Transmembrane inner ear expressed protein (TMIE)
• Gene Name: TMIE
• Related Disease:
  Nonsyndromic genetic hearing loss
  Autosomal recessive nonsyndromic hearing loss 6
  Sensorineural hearing loss disorder
  Hearing loss, autosomal recessive
• UniProt ID: TMIE_HUMAN
• Pfam ID: PF16038
• Sequence:
  MAGWPGAGPLCVLGGAALGVCLAGVAGQLVEPSTAPPKPKPPPLTKETVVFWDMRLWHVV
  GIFSLFVLSIIITLCCVFNCRVPRTRKEIEARYLQRKAAKMYTDKLETVPPLNELTEVPG
  EDKKKKKKKKKDSVDTVAIKVEEDEKNEAKKKKGEK
• Function: Unknown. The protein may play some role in a cellular membrane location. May reside within an internal membrane compartment and function in pathways such as those involved in protein and/or vesicle trafficking. Alternatively, the mature protein may be localized in the plasma membrane and serve as a site of interaction for other molecules through its highly charged C-terminal domain.
• Tissue Specificity: Expressed in many tissues.
• Reactome Pathway:
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)

Molecular Interaction Atlas (MIA) of This DOT

4 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 6	DIS8MY4S	Strong	Autosomal recessive	[2]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Biomarker	[3]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[4]

4 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 Transmembrane inner ear expressed protein (TMIE).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane inner ear expressed protein (TMIE).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane inner ear expressed protein (TMIE).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane inner ear expressed protein (TMIE).	[9]

2 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 increases the methylation of Transmembrane inner ear expressed protein (TMIE).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Transmembrane inner ear expressed protein (TMIE).	[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] Mutations in a novel gene, TMIE, are associated with hearing loss linked to the DFNB6 locus. Am J Hum Genet. 2002 Sep;71(3):632-6. doi: 10.1086/342193. Epub 2002 Jul 24.
• [3] An autosomal recessive nonsyndromic form of sensorineural hearing loss maps to 3p-DFNB6.Genome Res. 1995 Oct;5(3):305-8. doi: 10.1101/gr.5.3.305.
• [4] Genetic Hearing Loss Overview. 1999 Feb 14 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. Environ Epigenet. 2020 Dec 23;6(1):dvaa021. doi: 10.1093/eep/dvaa021. eCollection 2020.