Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5E0NE2)

• DOT Name: Alpha-tectorin (TECTA)
• Gene Name: TECTA
• Related Disease:
  Nonsyndromic genetic hearing loss
  Autosomal dominant nonsyndromic hearing loss 12
  Autosomal dominant nonsyndromic hearing loss 13
  Autosomal recessive nonsyndromic hearing loss 2
  Autosomal recessive nonsyndromic hearing loss 21
  Deafness
  Herpes zoster
  Stickler syndrome
  Stickler syndrome type 1
  Trichohepatoenteric syndrome
  Sensorineural hearing loss disorder
  Autosomal dominant nonsyndromic hearing loss
  Hearing loss, autosomal recessive
  Autosomal dominant nonsyndromic hearing loss 10
• UniProt ID: TECTA_HUMAN
• Pfam ID: PF08742 ; PF06119 ; PF01826 ; PF12714 ; PF00094 ; PF00100
• Sequence:
  MNYSSFLRIWVSFIFALVQHQAQPRELMYPFWQNDTKTPKVDDGSSSEIKLAIPVFFFGV
  PYRTVYVNNNGVVSFNVLVSQFTPESFPLTDGRAFVAPFWADVHNGIRGEIYYRETMEPA
  ILKRATKDIRKYFKDMATFSATWVFIVTWEEVTFYGGSSTTPVNTFQAVLVSDGSYTFTL
  FNYYEINWTTGTASGGDPLTGLGGVMAQAGFNGGNLTNFFSLPGSRTPEIVNIQETTNVN
  VPGRWAFKVDGKEIDPANGCTSRGQFLRRGEVFWDDLNCTVKCRCLDFNNEIYCQEASCS
  PYEVCEPKGKFFYCSAVETSTCVVFGEPHYHTFDGFLFHFQGSCAYLLARQCLQTSSLPF
  FSVEAKNEHRRGSAVSWVKELSVEVNGYKILIPKGSYGRVKVNDLVTSLPVTLDLGTVKI
  YQSGISTAVETDFGLLVTFDGQHYASISVPGSYINSTCGLCGNYNKNPLDDFLRPDGRPA
  MSVLDLGESWRVYHADWKCDSGCVDNCTQCDAATEALYFGSDYCGFLNKTDGPLWECGTV
  VDPTAFVHSCVYDLCSVRDNGTLLCQAIQAYALVCQALGIPIGDWRTQTGCVSTVQCPSF
  SHYSVCTSSCPDTCSDLTASRNCATPCTEGCECNQGFVLSTSQCVPLHKCGCDFDGHYYT
  MGEFFWATANCTVQCLCEEGGDVYCFNKTCGSGEVCAVEDGYQGCFPKRETVCLLSQNQV
  LHTFDGASYAFPSEFSYTLLKTCPERPEYLEIDINKKKPDAGPAWLRGLRILVADQEVKI
  GGIGASEVKLNGQEVELPFFHPSGKLEIYRNKNSTTVESKGVVTVQYSDIGLLYIRLSTT
  YFNCTGGLCGFYNANASDEFCLPNGKCTDNLAVFLESWTTFEEICNGECGDLLKACNNDS
  ELLKFYRSRSRCGIINDPSNSSFLECHGVVNVTAYYRTCLFRLCQSGGNESELCDSVARY
  ASACKNADVEVGPWRTYDFCPLECPENSHFEECITCTETCETLTLGPICVDSCSEGCQCD
  EGYALLGSQCVTRSECGCNFEGHQLATNETFWVDLDCQIFCYCSGTDNRVHCETIPCKDD
  EYCMEEGGLYYCQARTDASCIVSGYGHYLTFDGFPFDFQTSCPLILCTTGSRPSSDSFPK
  FVVTAKNEDRDPSLALWVKQVDVTVFGYSIVIHRAYKHTVLVNSERLYLPLKLGQGKINI
  FSFGFHVVVETDFGLKVVYDWKTFLSITVPRSMQNSTYGLCGRYNGNPDDDLEMPMGLLA
  SSVNEFGQSWVKRDTFCQVGCGDRCPSCAKVEGFSKVQQLCSLIPNQNAAFSKCHSKVNP
  TFFYKNCLFDSCIDGGAVQTACSWLQNYASTCQTQGITVTGWRNYTSCTVTCPPNSHYES
  CVSVCQPRCAAIRLKSDCSHYCVEGCHCDAGYVLNGKSCILPHSCGCYSDGKYYEPKQLF
  WNSDCTRRCRCFRRNVIQCDPRQCKSDEECALRNGVRGCFSTKTSYCLAAGGGVFRTFDG
  AFLRFPANCAFVLSTICQKLPDISFQLIINFDKWSAPNLTIISPVYFYINEEQILINDRN
  TVKVNGTQVNVPFITGLATKIYSSEGFLVIDTSPDIQIYYNGFNVIKISISERLQNKVCG
  LCGNFNGDLTDDYVTLRGKPVVSSVVLAQSWKTNGMQKRPLAPSCNELQFSQYAAMCDNV
  HIQKMQGDGYCLKLTDMKGFFQPCYGLLDPLPFYESCYLDGCYSHKKFQLCGSLAAYGEA
  CRSFGILSTEWIEKENCSGVVEDPCVGADCPNRTCELGNGRELCGCIEPPPYGNNSHDII
  DAEVTCKAAQMEVSISKCKLFQLGFEREGVRINDRQCTGIEGEDFISFQINNTKGNCGNI
  VQSNGTHIMYKNTLWIESANNTGNIITRDRTINVEFSCAYELDIKISLDSVVKPMLSVIN
  LTVPTQEGSFITKMALYKNASYKHPYRQGEVVLTTRDVLYVGVFVVGADATHLILTLNKC
  YATPTRDSNDKLRYFIIEGGCQNLKDNTIGIEENAVSLTCRFHVTVFKFIGDYDEVHLHC
  AVSLCDSEKYSCKITCPHNSRIATDYTKEPKEQIISVGPIRRKRLDWCEDNGGCEQICTS
  RVDGPLCSCVTGTLQEDGKSCRASNSSMELQVWTLLLIMIQISLWHFVYKSGTTS
• Function: One of the major non-collagenous components of the tectorial membrane. The tectorial membrane is an extracellular matrix of the inner ear that covers the neuroepithelium of the cochlea and contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

14 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 dominant nonsyndromic hearing loss 12	DISPBW4Z	Strong	Autosomal dominant	[2]
Autosomal dominant nonsyndromic hearing loss 13	DISFLETQ	Strong	Biomarker	[3]
Autosomal recessive nonsyndromic hearing loss 2	DIS1P51S	Strong	Genetic Variation	[4]
Autosomal recessive nonsyndromic hearing loss 21	DISW4CJG	Strong	Autosomal recessive	[2]
Deafness	DISKCLH4	Strong	Genetic Variation	[5]
Herpes zoster	DISNSMNY	Strong	Genetic Variation	[6]
Stickler syndrome	DISQWFHN	Strong	Biomarker	[7]
Stickler syndrome type 1	DIST5L4S	Strong	Biomarker	[7]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[8]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[9]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[10]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[10]
Autosomal dominant nonsyndromic hearing loss 10	DISBEWBO	Disputed	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Alpha-tectorin (TECTA).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Alpha-tectorin (TECTA).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the expression of Alpha-tectorin (TECTA).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Alpha-tectorin (TECTA).	[14]

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] A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback. Neuron. 2000 Oct;28(1):273-85. doi: 10.1016/s0896-6273(00)00102-1.
• [3] Research progress in pathogenic genes of hereditary non-syndromic mid-frequency deafness.Front Med. 2016 Jun;10(2):137-42. doi: 10.1007/s11684-016-0449-8. Epub 2016 May 3.
• [4] Hereditary deafness and phenotyping in humans.Br Med Bull. 2002;63:73-94. doi: 10.1093/bmb/63.1.73.
• [5] Genetic heterogeneity of congenital hearing impairment in Algerians from the Ghardaa province.Int J Pediatr Otorhinolaryngol. 2018 Sep;112:1-5. doi: 10.1016/j.ijporl.2018.06.012. Epub 2018 Jun 12.
• [6] A novel TECTA mutation in a Dutch DFNA8/12 family confirms genotype-phenotype correlation.J Assoc Res Otolaryngol. 2006 Jun;7(2):173-81. doi: 10.1007/s10162-006-0033-z. Epub 2006 Apr 25.
• [7] Audiometric characteristics of two Dutch families with non-ocular Stickler syndrome (COL11A2).Hear Res. 2012 Sep;291(1-2):15-23. doi: 10.1016/j.heares.2012.07.001. Epub 2012 Jul 14.
• [8] Expanding the Genetic Landscape of Usher-Like Phenotypes.Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4701-4710. doi: 10.1167/iovs.19-27470.
• [9] Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss.Orphanet J Rare Dis. 2017 Sep 25;12(1):157. doi: 10.1186/s13023-017-0708-z.
• [10] 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.
• [11] 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.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [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] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.