General Information of Drug Off-Target (DOT) (ID: OT0GTO1Z)

DOT Name Transmembrane protease serine 3 (TMPRSS3)
Synonyms EC 3.4.21.-; Serine protease TADG-12; Tumor-associated differentially-expressed gene 12 protein
Gene Name TMPRSS3
Related Disease
Nonsyndromic genetic hearing loss ( )
Advanced cancer ( )
Auditory neuropathy ( )
Autosomal recessive nonsyndromic hearing loss 16 ( )
Autosomal recessive nonsyndromic hearing loss 4 ( )
Autosomal recessive nonsyndromic hearing loss 8 ( )
Autosomal recessive nonsyndromic hearing loss 9 ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Deafness ( )
Epithelial ovarian cancer ( )
Glioma ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Pneumoconiosis ( )
Unverricht-Lundborg syndrome ( )
Autoimmune polyendocrine syndrome type 1 ( )
Movement disorder ( )
Hearing loss, autosomal recessive ( )
Gastric cancer ( )
Nasopharyngeal carcinoma ( )
Sensorineural hearing loss disorder ( )
Stomach cancer ( )
UniProt ID
TMPS3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.4.21.-
Pfam ID
PF00057 ; PF15494 ; PF00089
Sequence
MGENDPPAVEAPFSFRSLFGLDDLKISPVAPDADAVAAQILSLLPLKFFPIIVIGIIALI
LALAIGLGIHFDCSGKYRCRSSFKCIELIARCDGVSDCKDGEDEYRCVRVGGQNAVLQVF
TAASWKTMCSDDWKGHYANVACAQLGFPSYVSSDNLRVSSLEGQFREEFVSIDHLLPDDK
VTALHHSVYVREGCASGHVVTLQCTACGHRRGYSSRIVGGNMSLLSQWPWQASLQFQGYH
LCGGSVITPLWIITAAHCVYDLYLPKSWTIQVGLVSLLDNPAPSHLVEKIVYHSKYKPKR
LGNDIALMKLAGPLTFNEMIQPVCLPNSEENFPDGKVCWTSGWGATEDGAGDASPVLNHA
AVPLISNKICNHRDVYGGIISPSMLCAGYLTGGVDSCQGDSGGPLVCQERRLWKLVGATS
FGIGCAEVNKPGVYTRVTSFLDWIHEQMERDLKT
Function
Probable serine protease that plays a role in hearing. Acts as a permissive factor for cochlear hair cell survival and activation at the onset of hearing and is required for saccular hair cell survival. Activates ENaC (in vitro).
Tissue Specificity Expressed in many tissues including fetal cochlea. Isoform T is found at increased levels in some carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

26 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]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Auditory neuropathy DISM6GAU Strong Biomarker [3]
Autosomal recessive nonsyndromic hearing loss 16 DISQXGDY Strong Biomarker [3]
Autosomal recessive nonsyndromic hearing loss 4 DISCJIDF Strong Biomarker [3]
Autosomal recessive nonsyndromic hearing loss 8 DISR7AAN Strong Autosomal recessive [4]
Autosomal recessive nonsyndromic hearing loss 9 DISUKXHK Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Carcinoma DISH9F1N Strong Altered Expression [6]
Deafness DISKCLH4 Strong Biomarker [7]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [8]
Glioma DIS5RPEH Strong Biomarker [9]
Neoplasm DISZKGEW Strong Biomarker [10]
Ovarian cancer DISZJHAP Strong Altered Expression [8]
Ovarian neoplasm DISEAFTY Strong Altered Expression [8]
Pancreatic cancer DISJC981 Strong Altered Expression [2]
Pneumoconiosis DISSJLBN Strong Biomarker [11]
Unverricht-Lundborg syndrome DISG4WLX Strong Genetic Variation [12]
Autoimmune polyendocrine syndrome type 1 DISWJP8J moderate Genetic Variation [13]
Movement disorder DISOJJ2D moderate CausalMutation [14]
Hearing loss, autosomal recessive DIS8G9R9 Supportive Autosomal recessive [15]
Gastric cancer DISXGOUK Limited Biomarker [16]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [10]
Sensorineural hearing loss disorder DISJV45Z Limited Posttranslational Modification [17]
Stomach cancer DISKIJSX Limited Biomarker [16]
------------------------------------------------------------------------------------
⏷ Show the Full List of 26 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Transmembrane protease serine 3 (TMPRSS3). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Transmembrane protease serine 3 (TMPRSS3). [25]
------------------------------------------------------------------------------------
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Transmembrane protease serine 3 (TMPRSS3). [19]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Transmembrane protease serine 3 (TMPRSS3). [20]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Transmembrane protease serine 3 (TMPRSS3). [21]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Transmembrane protease serine 3 (TMPRSS3). [22]
Progesterone DMUY35B Approved Progesterone decreases the expression of Transmembrane protease serine 3 (TMPRSS3). [23]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of Transmembrane protease serine 3 (TMPRSS3). [24]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Transmembrane protease serine 3 (TMPRSS3). [26]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of Transmembrane protease serine 3 (TMPRSS3). [24]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Transmembrane protease serine 3 (TMPRSS3). [27]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Transmembrane protease serine 3 (TMPRSS3). [28]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Transmembrane protease serine 3 (TMPRSS3). [29]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 Drug(s)

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 novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer.Cancer Res. 2000 May 15;60(10):2602-6.
3 Hereditary deafness and phenotyping in humans.Br Med Bull. 2002;63:73-94. doi: 10.1093/bmb/63.1.73.
4 Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients. J Mol Med (Berl). 2002 Feb;80(2):124-31. doi: 10.1007/s00109-001-0310-6. Epub 2001 Dec 18.
5 Dysregulation of TMPRSS3 and TNFRSF11B correlates with tumorigenesis and poor prognosis in patients with breast cancer.Oncol Rep. 2017 Apr;37(4):2057-2062. doi: 10.3892/or.2017.5449. Epub 2017 Feb 14.
6 Ovarian tumor cells express a novel multi-domain cell surface serine protease.Biochim Biophys Acta. 2000 Nov 15;1502(3):337-50. doi: 10.1016/s0925-4439(00)00058-2.
7 Hereditary hearing loss: a 96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients.Gene. 2014 Jun 1;542(2):209-16. doi: 10.1016/j.gene.2014.03.033. Epub 2014 Mar 20.
8 A novel genome-based approach correlates TMPRSS3 overexpression in ovarian cancer with DNA hypomethylation.Gynecol Oncol. 2012 Jun;125(3):720-6. doi: 10.1016/j.ygyno.2012.03.026. Epub 2012 Mar 21.
9 Knockdown of TMPRSS3 inhibits cell proliferation, migration/invasion and induces apoptosis of glioma cells.J Cell Biochem. 2019 May;120(5):7794-7801. doi: 10.1002/jcb.28054. Epub 2018 Nov 15.
10 Knockdown of TMPRSS3, a Transmembrane Serine Protease, Inhibits Proliferation, Migration, and Invasion in Human Nasopharyngeal Carcinoma Cells.Oncol Res. 2018 Jan 19;26(1):95-101. doi: 10.3727/096504017X14920318811695. Epub 2017 Apr 12.
11 Pathway analysis for a genome-wide association study of pneumoconiosis.Toxicol Lett. 2015 Jan 5;232(1):284-92. doi: 10.1016/j.toxlet.2014.10.028. Epub 2014 Nov 4.
12 Coexistence of Unverricht-Lundborg disease and congenital deafness: molecular resolution of a complex comorbidity.Epilepsia. 2009 Jun;50(6):1612-5. doi: 10.1111/j.1528-1167.2008.01937.x. Epub 2008 Dec 15.
13 Characterization of a novel gene, C21orf2, on human chromosome 21q22.3 and its exclusion as the APECED gene by mutation analysis.Genomics. 1998 Jan 1;47(1):64-70. doi: 10.1006/geno.1997.5066.
14 Putative TMPRSS3/GJB2 digenic inheritance of hearing loss detected by targeted resequencing.Mol Cell Probes. 2017 Jun;33:24-27. doi: 10.1016/j.mcp.2017.03.001. Epub 2017 Mar 3.
15 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.
16 Knockdown of TMPRSS3 inhibits gastric cancer cell proliferation, invasion and EMT via regulation of the ERK1/2 and PI3K/Akt pathways.Biomed Pharmacother. 2018 Nov;107:841-848. doi: 10.1016/j.biopha.2018.08.023. Epub 2018 Aug 22.
17 TMPRSS3 regulates cell viability and apoptosis processes of HEI-OC1 cells via regulation of the circ-Slc4a2, miR-182 and Akt cascade.J Gene Med. 2019 Oct;21(10):e3118. doi: 10.1002/jgm.3118. Epub 2019 Sep 4.
18 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.
19 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
20 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.
21 Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocr Relat Cancer. 2008 Mar;15(1):161-73.
22 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
23 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
24 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
25 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.
26 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
27 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
28 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
29 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.