Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWY13GR)

• DOT Name: Teneurin-3 (TENM3)
• Synonyms: Ten-3; Protein Odd Oz/ten-m homolog 3; Tenascin-M3; Ten-m3; Teneurin transmembrane protein 3
• Gene Name: TENM3
• Related Disease:
  Microphthalmia
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Cocaine addiction
  Coloboma
  Colon cancer
  Colon carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Hepatitis B virus infection
  Intellectual disability
  Liver cirrhosis
  Microphthalmia, isolated, with coloboma 9
  Myocardial infarction
  Neoplasm of esophagus
  Schizophrenia
  Trigeminal neuralgia
  Hepatocellular carcinoma
  Neoplasm
  Microphthalmia, isolated, with coloboma
  Gallbladder cancer
  Gallbladder carcinoma
  Asthma
  Colorectal carcinoma
  Gastric cancer
  Metastatic malignant neoplasm
  Stomach cancer
• UniProt ID: TEN3_HUMAN
• Pfam ID: PF06484 ; PF15636
• Sequence:
  MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYG
  NRVKDLVHREADEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADT
  ENEAVMSPEHAMRLWGRGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQS
  TLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWV
  LGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVYSPPTRPLPRNTLSRSAFKFKK
  SSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENGKVNSDTMPT
  NTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNI
  SLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQARSVSLHEA
  GFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESVVECPRNCHGNGECVSGTCHCFPGFL
  GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCAC
  NSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQ
  ESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHG
  TCKDGKCECSQGWNGEHCTIEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETL
  CTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDR
  ISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQD
  GMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFV
  RPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKI
  TMTQSIIPFNLMKVHLMVAVVGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAVVS
  VGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFIS
  QQPPVVSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPS
  GNVTSVLELSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEVVAGT
  GEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGS
  NDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNNVVLQITENRQVRIAAGR
  PMHCQVPGVEYPVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISL
  VAGIPSECDCKNDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIRIRAVSK
  NKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSN
  GNTLRIRRDPNRMPVRVVSPDNQVIWLTIGTNGCLKSMTAQGLELVLFTYHGNSGLLATK
  SDETGWTTFFDYDSEGRLTNVTFPTGVVTNLHGDMDKAITVDIESSSREEDVSITSNLSS
  IDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPG
  ENGQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIA
  YDTSGHPTLWLPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTW
  SYTYLEKSMVLLLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPES
  NASIITDYNEEGLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTV
  NLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVINETPLP
  IDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMY
  WITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLH
  LLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKG
  SGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGH
  LFAMEISSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHG
  GLYDPLTKLIHFGERDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVK
  DYITDVNSWLVTFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQ
  AKAFLSLGKMAEVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVLNIANED
  CIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVS
  QSTTVVNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALARAWAREQQRV
  RDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRR
• Function: Involved in neural development by regulating the establishment of proper connectivity within the nervous system. Acts in both pre- and postsynaptic neurons in the hippocampus to control the assembly of a precise topographic projection: required in both CA1 and subicular neurons for the precise targeting of proximal CA1 axons to distal subiculum, probably by promoting homophilic cell adhesion. Required for proper dendrite morphogenesis and axon targeting in the vertebrate visual system, thereby playing a key role in the development of the visual pathway. Regulates the formation in ipsilateral retinal mapping to both the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). May also be involved in the differentiation of the fibroblast-like cells in the superficial layer of mandibular condylar cartilage into chondrocytes.
• Tissue Specificity: Expressed in adult and fetal brain, slightly lower levels in testis and ovary, and intermediate levels in all other peripheral tissues examined. Not expressed in spleen or liver. Expression was high in brain, with highest levels in amygdala and caudate nucleus, followed by thalamus and subthalamic nucleus.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microphthalmia	DISGEBES	Definitive	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[4]
Cocaine addiction	DISHTRXG	Strong	Biomarker	[5]
Coloboma	DISP39N5	Strong	Genetic Variation	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[9]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[1]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[10]
Microphthalmia, isolated, with coloboma 9	DISDG771	Strong	Autosomal recessive	[11]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[12]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[4]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[13]
Trigeminal neuralgia	DIS31ZY6	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	moderate	Genetic Variation	[15]
Neoplasm	DISZKGEW	moderate	Genetic Variation	[2]
Microphthalmia, isolated, with coloboma	DISLSEUJ	Supportive	Autosomal dominant	[16]
Gallbladder cancer	DISXJUAF	Disputed	Biomarker	[17]
Gallbladder carcinoma	DISD6ACL	Disputed	Biomarker	[17]
Asthma	DISW9QNS	Limited	Genetic Variation	[18]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[19]
Gastric cancer	DISXGOUK	Limited	Biomarker	[20]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[20]
Stomach cancer	DISKIJSX	Limited	Biomarker	[20]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Teneurin-3 (TENM3) affects the response to substance of Cocaine.	[5]

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 Teneurin-3 (TENM3).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Teneurin-3 (TENM3).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Teneurin-3 (TENM3).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Teneurin-3 (TENM3).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Teneurin-3 (TENM3).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Teneurin-3 (TENM3).	[25]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Teneurin-3 (TENM3).	[26]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Teneurin-3 (TENM3).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Teneurin-3 (TENM3).	[28]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Teneurin-3 (TENM3).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Teneurin-3 (TENM3).	[31]

References

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• [2] Clinical features of pulmonary embolism in patients with lung cancer: A meta-analysis.PLoS One. 2019 Sep 30;14(9):e0223230. doi: 10.1371/journal.pone.0223230. eCollection 2019.
• [3] The hepatocyte growth factor regulatory factors in human breast cancer.Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):202-11. doi: 10.1158/1078-0432.ccr-0553-3.
• [4] Prognostic significance and role in TNM stage of tumor deposits in esophageal cancer.J Thorac Dis. 2017 Nov;9(11):4461-4476. doi: 10.21037/jtd.2017.10.60.
• [5] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [6] The genetic architecture of microphthalmia, anophthalmia and coloboma. Eur J Med Genet. 2014 Aug;57(8):369-80. doi: 10.1016/j.ejmg.2014.05.002. Epub 2014 May 22.
• [7] Relationship between LAPTM4B Gene Polymorphism and Prognosis of Patients following Tumor Resection for Colorectal and Esophageal Cancers.PLoS One. 2016 Jul 8;11(7):e0158715. doi: 10.1371/journal.pone.0158715. eCollection 2016.
• [8] Upregulated long non-coding RNA SBF2-AS1 promotes proliferation in esophageal squamous cell carcinoma.Oncol Lett. 2018 Apr;15(4):5071-5080. doi: 10.3892/ol.2018.7968. Epub 2018 Feb 6.
• [9] Correlations of pri-Let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer after transcatheter arterial chemoembolization.Pathol Res Pract. 2018 May;214(5):667-672. doi: 10.1016/j.prp.2018.03.022. Epub 2018 Mar 26.
• [10] Long noncoding RNA HOTTIP promotes hepatocellular carcinoma tumorigenesis and development: A comprehensive investigation based on bioinformatics, qRTPCR and metaanalysis of 393 cases.Int J Oncol. 2017 Dec;51(6):1705-1721. doi: 10.3892/ijo.2017.4164. Epub 2017 Oct 16.
• [11] Novel truncating mutation in TENM3 in siblings with motor developmental delay, ocular coloboma, oval cornea, without microphthalmia. Am J Med Genet A. 2018 Dec;176(12):2930-2933. doi: 10.1002/ajmg.a.40658. Epub 2018 Dec 4.
• [12] Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium.PLoS One. 2016 Mar 7;11(3):e0144997. doi: 10.1371/journal.pone.0144997. eCollection 2016.
• [13] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [14] Negative/low HER2 expression alone or combined with E-cadherin positivity is predictive of better prognosis in patients with breast carcinoma.Histol Histopathol. 2012 Mar;27(3):377-85. doi: 10.14670/HH-27.377.
• [15] CXCL13 rather than IL-31 is a potential indicator in patients with hepatocellular carcinoma.Cytokine. 2017 Jan;89:91-97. doi: 10.1016/j.cyto.2016.08.016. Epub 2016 Sep 20.
• [16] Homozygous null mutation in ODZ3 causes microphthalmia in humans. Genet Med. 2012 Nov;14(11):900-4. doi: 10.1038/gim.2012.71. Epub 2012 Jul 5.
• [17] Laparoscopy versus laparotomy approach of a radical resection for gallbladder cancer: a retrospective comparative study.Surg Endosc. 2020 Jul;34(7):2926-2938. doi: 10.1007/s00464-019-07075-4. Epub 2019 Aug 28.
• [18] Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.Toxicol Sci. 2015 Jul;146(1):192-201. doi: 10.1093/toxsci/kfv084. Epub 2015 Apr 26.
• [19] Th17 cytokine profiling of colorectal cancer patients with or without enterovirus 71 antigen expression.Cytokine. 2018 Jul;107:35-42. doi: 10.1016/j.cyto.2017.11.012. Epub 2017 Nov 23.
• [20] AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by activating the NF-B pathway and predicts poor outcome of the patients.Sci Rep. 2018 Aug 10;8(1):11955. doi: 10.1038/s41598-018-29878-6.
• [21] 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.
• [22] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [23] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [24] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [25] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [26] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [27] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [28] 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.
• [29] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [30] 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.
• [31] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [32] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.