Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3UNZZY)

• DOT Name: Nanos homolog 1 (NANOS1)
• Synonyms: NOS-1; EC_Rep1a
• Gene Name: NANOS1
• Related Disease:
  Anxiety
  Anxiety disorder
  Autism spectrum disorder
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Liver cirrhosis
  Malignant mesothelioma
  Neoplasm
  Obstructive sleep apnea
  Schizophrenia
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Male infertility with teratozoospermia due to single gene mutation
  Sickle-cell anaemia
  Spermatogenic failure 12
• UniProt ID: NANO1_HUMAN
• PDB ID: 4CQO
• Pfam ID: PF05741
• Sequence:
  MEAFPWAPRSPRRGRAPPPMALVPSARYVSAPGPAHPQPFSSWNDYLGLATLITKAVDGE
  PRFGCARGGNGGGGSPPSSSSSSCCSPHTGAGPGALGPALGPPDYDEDDDDDSDEPGSRG
  RYLGSALELRALELCAGPAEAGLLEERFAELSPFAGRAAAVLLGCAPAAAAAATTTSEAT
  PREERAPAWAAEPRLHAASGAAAARLLKPELQVCVFCRNNKEAMALYTTHILKGPDGRVL
  CPVLRRYTCPLCGASGDNAHTIKYCPLSKVPPPPARPPPRSARDGPPGKKLR
• Function: May act as a translational repressor which regulates translation of specific mRNAs by forming a complex with PUM2 that associates with the 3'-UTR of mRNA targets. Capable of interfering with the proadhesive and anti-invasive functions of E-cadherin. Up-regulates the production of MMP14 to promote tumor cell invasion.
• Tissue Specificity: Testis and ovary (at protein level). Predominantly expressed in testis. Specifically expressed during germline development. In adult tissues, it is mainly expressed in spermatogonia, the stem cells of the germline. Also expressed during meiosis in spermatocytes. Not present in late, post-meiotic stage germ cells. Expressed in fetal ovaries, while it is weakly or not expressed in mature postmeiotic oocytes, suggesting that it may be expressed in premeiotic female germ cells. Expressed at high levels only in the E-cadherin deficient cell lines. Highly expressed in lung carcinomas and mostly detected in invasive tumor cells and its expression correlates with tumor aggressiveness.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Definitive	Genetic Variation	[1]
Anxiety disorder	DISBI2BT	Definitive	Genetic Variation	[1]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[2]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[5]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Obstructive sleep apnea	DIS0SVD1	Strong	Genetic Variation	[7]
Schizophrenia	DISSRV2N	Strong	Biomarker	[8]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Supportive	Autosomal dominant	[9]
Male infertility with teratozoospermia due to single gene mutation	DISPY5W6	Disputed	GermlineCausalMutation	[9]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[10]
Spermatogenic failure 12	DISOX567	Limited	Unknown	[9]

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 Nanos homolog 1 (NANOS1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nanos homolog 1 (NANOS1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nanos homolog 1 (NANOS1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nanos homolog 1 (NANOS1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nanos homolog 1 (NANOS1).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nanos homolog 1 (NANOS1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nanos homolog 1 (NANOS1).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nanos homolog 1 (NANOS1).	[17]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Nanos homolog 1 (NANOS1).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Nanos homolog 1 (NANOS1).	[19]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Nanos homolog 1 (NANOS1).	[20]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Nanos homolog 1 (NANOS1).	[21]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Nanos homolog 1 (NANOS1).	[22]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Nanos homolog 1 (NANOS1).	[23]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Nanos homolog 1 (NANOS1).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nanos homolog 1 (NANOS1).	[24]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Nanos homolog 1 (NANOS1).	[25]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Nanos homolog 1 (NANOS1).	[26]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Nanos homolog 1 (NANOS1).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nanos homolog 1 (NANOS1).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nanos homolog 1 (NANOS1).	[29]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Nanos homolog 1 (NANOS1).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Nanos homolog 1 (NANOS1).	[23]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Nanos homolog 1 (NANOS1).	[30]

References

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• [2] Family-based association study between NOS-I and -IIA polymorphisms and autism spectrum disorders in Korean trios.Am J Med Genet B Neuropsychiatr Genet. 2009 Mar 5;150B(2):300-6. doi: 10.1002/ajmg.b.30798.
• [3] Oedema extension in cerebral metastasis and correlation with the expression of nitric oxide synthase isozymes (NOS I-III).Anticancer Res. 2000 Jan-Feb;20(1A):305-10.
• [4] E-cadherin regulates human Nanos1, which interacts with p120ctn and induces tumor cell migration and invasion.Cancer Res. 2006 Oct 15;66(20):10007-15. doi: 10.1158/0008-5472.CAN-05-3096.
• [5] Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock-out mice and is elevated in murine and human cirrhosis.Liver Int. 2004 Aug;24(4):345-53. doi: 10.1111/j.1478-3231.2004.0933.x.
• [6] MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.Biomed Res Int. 2015;2015:635748. doi: 10.1155/2015/635748. Epub 2015 Feb 1.
• [7] Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea.BMC Med Genomics. 2013 Sep 6;6:29. doi: 10.1186/1755-8794-6-29.
• [8] Interaction of NOS1AP with the NOS-I PDZ domain: Implications for schizophrenia-related alterations in dendritic morphology.Eur Neuropsychopharmacol. 2016 Apr;26(4):741-55. doi: 10.1016/j.euroneuro.2016.01.008. Epub 2016 Jan 28.
• [9] Mutations of NANOS1, a human homologue of the Drosophila morphogen, are associated with a lack of germ cells in testes or severe oligo-astheno-teratozoospermia. J Med Genet. 2013 Mar;50(3):187-93. doi: 10.1136/jmedgenet-2012-101230. Epub 2013 Jan 12.
• [10] Low exhaled nitric oxide and a polymorphism in the NOS I gene is associated with acute chest syndrome.Am J Respir Crit Care Med. 2001 Dec 15;164(12):2186-90. doi: 10.1164/ajrccm.164.12.2012090.
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• [18] 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.
• [19] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [20] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [21] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [22] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [23] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
• [26] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [27] 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.
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• [30] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.