Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNRLO7G)

DOT Name Neuronatin (NNAT)
Gene Name NNAT
Related Disease
Angelman syndrome ( )
Breast cancer ( )
Breast carcinoma ( )
Anorexia nervosa cachexia ( )
Bone disease ( )
Eating disorder ( )
Estrogen-receptor positive breast cancer ( )
Ewing sarcoma ( )
Fragile X syndrome ( )
Hepatocellular carcinoma ( )
Huntington disease ( )
Lafora disease ( )
Medulloblastoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoporosis ( )
Pleomorphic sarcoma ( )
Rheumatoid arthritis ( )
Type-1/2 diabetes ( )
Adenocarcinoma ( )
Lung adenocarcinoma ( )
Small-cell lung cancer ( )
Squamous cell carcinoma ( )
Thyroid gland papillary carcinoma ( )
Acute leukaemia ( )
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Childhood kidney Wilms tumor ( )
leukaemia ( )
Leukemia ( )
Myelodysplastic/myeloproliferative neoplasm ( )
Wilms tumor ( )
UniProt ID
NNAT_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MAAVAAASAELLIIGWYIFRVLLQVFLECCIYWVGFAFRNPPGTQPIARSEVFRYSLQKL
AYTVSRTGRQVLGERRQRAPN
Function
May participate in the maintenance of segment identity in the hindbrain and pituitary development, and maturation or maintenance of the overall structure of the nervous system. May function as a regulatory subunit of ion channels.

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Angelman syndrome DIS4QVXO Definitive Biomarker [1]
Breast cancer DIS7DPX1 Definitive Altered Expression [2]
Breast carcinoma DIS2UE88 Definitive Altered Expression [2]
Anorexia nervosa cachexia DISFO5RQ Strong Genetic Variation [3]
Bone disease DISE1F82 Strong Biomarker [4]
Eating disorder DISVGXN0 Strong Genetic Variation [3]
Estrogen-receptor positive breast cancer DIS1H502 Strong Altered Expression [2]
Ewing sarcoma DISQYLV3 Strong Biomarker [5]
Fragile X syndrome DISE8W3A Strong Altered Expression [6]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [7]
Huntington disease DISQPLA4 Strong Altered Expression [8]
Lafora disease DIS83JHH Strong Biomarker [9]
Medulloblastoma DISZD2ZL Strong Biomarker [10]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [11]
Neoplasm DISZKGEW Strong Altered Expression [12]
Neuroblastoma DISVZBI4 Strong Altered Expression [13]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [14]
Obesity DIS47Y1K Strong Altered Expression [15]
Osteoporosis DISF2JE0 Strong Biomarker [4]
Pleomorphic sarcoma DISXU8CC Strong Altered Expression [16]
Rheumatoid arthritis DISTSB4J Strong Biomarker [4]
Type-1/2 diabetes DISIUHAP Strong Biomarker [9]
Adenocarcinoma DIS3IHTY moderate Altered Expression [17]
Lung adenocarcinoma DISD51WR moderate Altered Expression [17]
Small-cell lung cancer DISK3LZD moderate Biomarker [18]
Squamous cell carcinoma DISQVIFL moderate Altered Expression [17]
Thyroid gland papillary carcinoma DIS48YMM Disputed Altered Expression [12]
Acute leukaemia DISDQFDI Limited Genetic Variation [19]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [19]
Advanced cancer DISAT1Z9 Limited Biomarker [9]
Childhood kidney Wilms tumor DIS0NMK3 Limited Altered Expression [20]
leukaemia DISS7D1V Limited Genetic Variation [19]
Leukemia DISNAKFL Limited Posttranslational Modification [19]
Myelodysplastic/myeloproliferative neoplasm DISDHXQ4 Limited Biomarker [19]
Wilms tumor DISB6T16 Limited Altered Expression [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 35 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Neuronatin (NNAT). [21]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Neuronatin (NNAT). [22]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Neuronatin (NNAT). [23]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Neuronatin (NNAT). [24]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Neuronatin (NNAT). [13]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Neuronatin (NNAT). [26]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Neuronatin (NNAT). [27]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Neuronatin (NNAT). [28]
Lidocaine DML4ZOT Approved Lidocaine decreases the expression of Neuronatin (NNAT). [29]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Neuronatin (NNAT). [30]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID increases the expression of Neuronatin (NNAT). [31]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 Drug(s)

References

1 Down-Regulation of miRNA-708 Promotes Aberrant Calcium Signaling by Targeting Neuronatin in a Mouse Model of Angelman Syndrome.Front Mol Neurosci. 2019 Feb 13;12:35. doi: 10.3389/fnmol.2019.00035. eCollection 2019.
2 Neuronatin is a modifier of estrogen receptor-positive breast cancer incidence and outcome.Breast Cancer Res Treat. 2019 Aug;177(1):77-91. doi: 10.1007/s10549-019-05307-8. Epub 2019 Jun 4.
3 Anorexia nervosa is associated with Neuronatin variants.Psychiatr Genet. 2019 Aug;29(4):103-110. doi: 10.1097/YPG.0000000000000224.
4 Development of PEGylated carboxylic acid-modified polyamidoamine dendrimers as bone-targeting carriers for the treatment of bone diseases.J Control Release. 2017 Sep 28;262:10-17. doi: 10.1016/j.jconrel.2017.07.018. Epub 2017 Jul 11.
5 Pharmacologic inhibition of epigenetic modification reveals targets of aberrant promoter methylation in Ewing sarcoma.Pediatr Blood Cancer. 2013 Sep;60(9):1437-46. doi: 10.1002/pbc.24526. Epub 2013 Mar 18.
6 Integrated transcriptome analysis of human iPS cells derived from a fragile X syndrome patient during neuronal differentiation.Sci China Life Sci. 2016 Nov;59(11):1093-1105. doi: 10.1007/s11427-016-0194-6. Epub 2016 Oct 11.
7 Pegylated recombinant human arginase (rhArg-peg5,000mw) inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion.Cancer Res. 2007 Jan 1;67(1):309-17. doi: 10.1158/0008-5472.CAN-06-1945.
8 Decreased striatal RGS2 expression is neuroprotective in Huntington's disease (HD) and exemplifies a compensatory aspect of HD-induced gene regulation.PLoS One. 2011;6(7):e22231. doi: 10.1371/journal.pone.0022231. Epub 2011 Jul 14.
9 Neuronatin gene: Imprinted and misfolded: Studies in Lafora disease, diabetes and cancer may implicate NNAT-aggregates as a common downstream participant in neuronal loss.Genomics. 2014 Feb-Mar;103(2-3):183-8. doi: 10.1016/j.ygeno.2013.12.001. Epub 2013 Dec 15.
10 Coexpression of neuronatin splice forms promotes medulloblastoma growth.Neuro Oncol. 2008 Oct;10(5):716-24. doi: 10.1215/15228517-2008-038. Epub 2008 Aug 13.
11 Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration.Cancer Cell. 2013 Jan 14;23(1):63-76. doi: 10.1016/j.ccr.2012.11.019.
12 Differences in the transcriptome of medullary thyroid cancer regarding the status and type of RET gene mutations.Sci Rep. 2017 Feb 9;7:42074. doi: 10.1038/srep42074.
13 High expressions of neuronatin isoforms in favorable neuroblastoma. J Pediatr Hematol Oncol. 2007 Aug;29(8):551-6. doi: 10.1097/MPH.0b013e3181256b7b.
14 Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer.Oncogene. 2007 Apr 19;26(18):2621-34. doi: 10.1038/sj.onc.1210041. Epub 2006 Oct 9.
15 Neuronatin deletion causes postnatal growth restriction and adult obesity in 129S2/Sv mice.Mol Metab. 2018 Dec;18:97-106. doi: 10.1016/j.molmet.2018.09.001. Epub 2018 Sep 15.
16 Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.Genome Biol. 2013 Dec 17;14(12):r137. doi: 10.1186/gb-2013-14-12-r137.
17 Neuronatin expression and its clinicopathological significance in pulmonary non-small cell carcinoma.J Thorac Oncol. 2007 Sep;2(9):796-801. doi: 10.1097/JTO.0b013e318145af5e.
18 Analysis of differentially expressed genes in neuroendocrine carcinomas of the lung.J Thorac Oncol. 2006 Oct;1(8):780-6.
19 Hypermethylation of the imprinted NNAT locus occurs frequently in pediatric acute leukemia.Carcinogenesis. 2002 Apr;23(4):559-64. doi: 10.1093/carcin/23.4.559.
20 Selective methylation of CpGs at regulatory binding sites controls NNAT expression in Wilms tumors.PLoS One. 2013 Jun 25;8(6):e67605. doi: 10.1371/journal.pone.0067605. Print 2013.
21 Effects of valproic acid on gene expression during human embryonic stem cell differentiation into neurons. J Toxicol Sci. 2014 Jun;39(3):383-90. doi: 10.2131/jts.39.383.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
24 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
25 High expressions of neuronatin isoforms in favorable neuroblastoma. J Pediatr Hematol Oncol. 2007 Aug;29(8):551-6. doi: 10.1097/MPH.0b013e3181256b7b.
26 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
27 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
28 Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
29 Lidocaine prevents breast cancer growth by targeting neuronatin to inhibit nerve fibers formation. J Toxicol Sci. 2021;46(7):329-339. doi: 10.2131/jts.46.329.
30 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
31 Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.