Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFM2IDJ)

• DOT Name: Nanos homolog 2 (NANOS2)
• Synonyms: NOS-2
• Gene Name: NANOS2
• Related Disease:
  Advanced cancer
  Benign prostatic hyperplasia
  Prostatitis
  Arteriosclerosis
  Atherosclerosis
  Cerebral palsy
  Congestive heart failure
  Cryptorchidism
  Hepatocellular carcinoma
  Male infertility
  Medullary thyroid gland carcinoma
  Primary sclerosing cholangitis
  Systemic sclerosis
  Neoplasm
  Common cold
  Lung cancer
  Lung carcinoma
  Ocular hypertension
• UniProt ID: NANO2_HUMAN
• Pfam ID: PF05741
• Sequence:
  MQLPPFDMWKDYFNLSQVVWALIASRGQRLETQEIEEPSPGPPLGQDQGLGAPGANGGLG
  TLCNFCKHNGESRHVYSSHQLKTPDGVVVCPILRHYVCPVCGATGDQAHTLKYCPLNGGQ
  QSLYRRSGRNSAGRRVKR
• Function: Plays a key role in the sexual differentiation of germ cells by promoting the male fate but suppressing the female fate. Represses the female fate pathways by suppressing meiosis, which in turn results in the promotion of the male fate. Maintains the suppression of meiosis by preventing STRA8 expression, which is required for premeiotic DNA replication, after CYP26B1 is decreased. Regulates the localization of the CCR4-NOT deadenylation complex to P-bodies and plays a role in recruiting the complex to trigger the degradation of mRNAs involved in meiosis. Required for the maintenance of the spermatogonial stem cell population. Not essential for the assembly of P-bodies but is required for the maintenance of their normal state.
• Tissue Specificity: Testis and ovary. Expression found in several spermatogenic stages: in cells on the periphery of the tubules which could correspond to spermatogonia, in spermatocytes and in round spermatids (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Benign prostatic hyperplasia	DISI3CW2	Definitive	Altered Expression	[2]
Prostatitis	DISL8OGN	Definitive	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Cerebral palsy	DIS82ODL	Strong	Genetic Variation	[4]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[5]
Cryptorchidism	DISYUD2P	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[6]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Biomarker	[7]
Primary sclerosing cholangitis	DISTH5WJ	Strong	Biomarker	[8]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	moderate	Genetic Variation	[10]
Common cold	DIS3MADM	Limited	Altered Expression	[11]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[10]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[10]
Ocular hypertension	DISC2BT9	Limited	Biomarker	[12]

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 2 (NANOS2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nanos homolog 2 (NANOS2).	[14]

References

• [1] Decreased levels of nitric oxide production and nitric oxide synthase-2 expression are associated with the development and metastasis of hepatocellular carcinoma.Mol Med Rep. 2012 Dec;6(6):1261-6. doi: 10.3892/mmr.2012.1096. Epub 2012 Sep 24.
• [2] Nitric oxide synthases in normal and benign hyperplastic human prostate: immunohistochemistry and molecular biology.J Pathol. 1999 Oct;189(2):224-9. doi: 10.1002/(SICI)1096-9896(199910)189:2<224::AID-PATH422>3.0.CO;2-K.
• [3] Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques.Cardiovasc Res. 1999 Aug 15;43(3):744-54. doi: 10.1016/s0008-6363(99)00148-0.
• [4] Association Between rs3833912/rs16944 SNPs and Risk for Cerebral Palsy in Mexican Children.Mol Neurobiol. 2019 Mar;56(3):1800-1811. doi: 10.1007/s12035-018-1178-6. Epub 2018 Jun 21.
• [5] Inducible nitric oxide synthase in skeletal muscle of patients with chronic heart failure.J Am Coll Cardiol. 1998 Oct;32(4):964-9. doi: 10.1016/s0735-1097(98)00335-0.
• [6] miR-34c disrupts spermatogonial stem cell homeostasis in cryptorchid testes by targeting Nanos2.Reprod Biol Endocrinol. 2018 Oct 15;16(1):97. doi: 10.1186/s12958-018-0417-z.
• [7] Gene therapy of rat medullary thyroid cancer by naked nitric oxide synthase II DNA injection.J Gene Med. 2000 Sep-Oct;2(5):344-52. doi: 10.1002/1521-2254(200009/10)2:5<344::AID-JGM124>3.0.CO;2-3.
• [8] Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes.Gastroenterology. 2003 Mar;124(3):737-53. doi: 10.1053/gast.2003.50100.
• [9] Serum nitric oxide (NO) levels in systemic sclerosis patients: correlation between NO levels and clinical features.Clin Exp Immunol. 2003 Dec;134(3):538-44. doi: 10.1111/j.1365-2249.2003.02320.x.
• [10] The (CCTTT)n microsatellite polymorphism in the NOS2 gene may influence lung cancer risk and long-term survival, especially in non-smokers.Tumour Biol. 2014 May;35(5):4425-34. doi: 10.1007/s13277-013-1582-5. Epub 2014 Jan 10.
• [11] Rhinovirus infection induces expression of type 2 nitric oxide synthase in human respiratory epithelial cells in vitro and in vivo.J Allergy Clin Immunol. 2001 Feb;107(2):235-43. doi: 10.1067/mai.2001.112028.
• [12] Evaluation of inducible nitric oxide synthase in glaucomatous optic neuropathy and pressure-induced optic nerve damage.Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1313-21. doi: 10.1167/iovs.04-0829.
• [13] 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.
• [14] 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.