Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYBYJ82)

DOT Name	Necdin (NDN)
Gene Name	NDN
Related Disease	Angelman syndrome ( ) Breast neoplasm ( ) Carcinoma ( ) Neoplasm ( ) Undifferentiated carcinoma ( ) Adult glioblastoma ( ) Advanced cancer ( ) Autism ( ) Bardet biedl syndrome ( ) Brain disease ( ) Colorectal carcinoma ( ) Epithelial ovarian cancer ( ) Glioblastoma multiforme ( ) Graves disease ( ) Head-neck squamous cell carcinoma ( ) Hereditary sensory and autonomic neuropathy type 4 ( ) Hypogonadotropic hypogonadism ( ) Hypogonadotropic hypogonadism 7 with or without anosmia ( ) Kallmann syndrome ( ) Klinefelter syndrome ( ) Mental disorder ( ) Neuroblastoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Squamous cell carcinoma ( ) Systemic sclerosis ( ) Testicular cancer ( ) Transitional cell carcinoma ( ) Urothelial carcinoma ( ) Breast cancer ( ) Breast carcinoma ( ) leukaemia ( ) Leukemia ( ) Melanoma ( ) Parkinson disease ( ) Obesity ( ) Rett syndrome ( )
UniProt ID	NECD_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01454
Sequence	MSEQSKDLSDPNFAAEAPNSEVHSSPGVSEGVPPSATLAEPQSPPLGPTAAPQAAPPPQA PNDEGDPKALQQAAEEGRAHQAPSAAQPGPAPPAPAQLVQKAHELMWYVLVKDQKKMIIW FPDMVKDVIGSYKKWCRSILRRTSLILARVFGLHLRLTSLHTMEFALVKALEPEELDRVA LSNRMPMTGLLLMILSLIYVKGRGARESAVWNVLRILGLRPWKKHSTFGDVRKLITEEFV QMNYLKYQRVPYVEPPEYEFFWGSRASREITKMQIMEFLARVFKKDPQAWPSRYREALEE ARALREANPTAHYPRSSVSED
Function	Growth suppressor that facilitates the entry of the cell into cell cycle arrest. Functionally similar to the retinoblastoma protein it binds to and represses the activity of cell-cycle-promoting proteins such as SV40 large T antigen, adenovirus E1A, and the transcription factor E2F. Necdin also interacts with p53 and works in an additive manner to inhibit cell growth. Also functions as a transcription factor and directly binds to specific guanosine-rich DNA sequences.
Tissue Specificity	Almost ubiquitous. Detected in fetal brain, lung, liver and kidney; in adult heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon. Not detected in peripheral blood leukocytes. In brain, restricted to post-mitotic neurons.
Reactome Pathway	Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 )

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Angelman syndrome	DIS4QVXO	Definitive	Biomarker	[1]
Breast neoplasm	DISNGJLM	Definitive	Biomarker	[2]
Carcinoma	DISH9F1N	Definitive	Biomarker	[3]
Neoplasm	DISZKGEW	Definitive	Biomarker	[4]
Undifferentiated carcinoma	DISIAZST	Definitive	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Autism	DISV4V1Z	Strong	Biomarker	[6]
Bardet biedl syndrome	DISTBNZW	Strong	Biomarker	[7]
Brain disease	DIS6ZC3X	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Graves disease	DISU4KOQ	Strong	Biomarker	[10]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Posttranslational Modification	[11]
Hereditary sensory and autonomic neuropathy type 4	DISNE3R5	Strong	Biomarker	[12]
Hypogonadotropic hypogonadism	DIS8JSKR	Strong	Biomarker	[13]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Strong	Genetic Variation	[13]
Kallmann syndrome	DISO3HDG	Strong	Genetic Variation	[13]
Klinefelter syndrome	DISOUI7W	Strong	Biomarker	[13]
Mental disorder	DIS3J5R8	Strong	Biomarker	[14]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[11]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[16]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[17]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[18]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[18]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[2]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[2]
leukaemia	DISS7D1V	moderate	Biomarker	[19]
Leukemia	DISNAKFL	moderate	Biomarker	[19]
Melanoma	DIS1RRCY	moderate	Biomarker	[20]
Parkinson disease	DISQVHKL	Disputed	Altered Expression	[15]
Obesity	DIS47Y1K	Limited	Biomarker	[21]
Rett syndrome	DISGG5UV	Limited	Biomarker	[22]
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⏷ Show the Full List of 37 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 Necdin (NDN).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Necdin (NDN).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Necdin (NDN).	[30]
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5 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 Necdin (NDN).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Necdin (NDN).	[25]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Necdin (NDN).	[26]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Necdin (NDN).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Necdin (NDN).	[29]
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References

1	Physical mapping studies at D15S10: implications for candidate gene identification in the Angelman syndrome/Prader-Willi syndrome chromosome region of 15q11-q13.Genomics. 1994 Jan 1;19(1):170-2. doi: 10.1006/geno.1994.1031.
2	Necdin is a breast cancer metastasis suppressor that regulates the transcription of c-Myc.Oncotarget. 2015 Oct 13;6(31):31557-68. doi: 10.18632/oncotarget.5230.
3	Methylation silencing of angiopoietin-like 4 in rat and human mammary carcinomas.Cancer Sci. 2011 Jul;102(7):1337-43. doi: 10.1111/j.1349-7006.2011.01955.x. Epub 2011 May 12.
4	NDN is an imprinted tumor suppressor gene that is downregulated in ovarian cancers through genetic and epigenetic mechanisms.Oncotarget. 2016 Jan 19;7(3):3018-32. doi: 10.18632/oncotarget.6576.
5	Network modeling of the transcriptional effects of copy number aberrations in glioblastoma.Mol Syst Biol. 2011 Apr 26;7:486. doi: 10.1038/msb.2011.17.
6	Duplication of the 15q11-q13 region: clinical and genetic study of 30 new cases.Eur J Med Genet. 2014 Jan;57(1):5-14. doi: 10.1016/j.ejmg.2013.10.008. Epub 2013 Nov 12.
7	Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth.Hum Mol Genet. 2005 Mar 1;14(5):627-37. doi: 10.1093/hmg/ddi059. Epub 2005 Jan 13.
8	The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse.Hum Mol Genet. 1997 Oct;6(11):1873-8. doi: 10.1093/hmg/6.11.1873.
9	Hypermethylation of NDN promotes cell proliferation by activating the Wnt signaling pathway in colorectal cancer.Oncotarget. 2017 Jul 11;8(28):46191-46203. doi: 10.18632/oncotarget.17580.
10	Accumulation of identical T cell clones in the right and left lobes of the thyroid gland in patients with Graves' disease: analysis of T cell clonotype in vivo.Endocr J. 2000 Apr;47(2):127-36. doi: 10.1507/endocrj.47.127.
11	NDN and CD1A are novel prognostic methylation markers in patients with head and neck squamous carcinomas.BMC Cancer. 2015 Oct 30;15:825. doi: 10.1186/s12885-015-1806-8.
12	Novel NTRK1 Frameshift Mutation in Congenital Insensitivity to Pain With Anhidrosis.J Child Neurol. 2015 Sep;30(10):1357-61. doi: 10.1177/0883073814552438. Epub 2014 Oct 14.
13	Mutational analysis of the necdin gene in patients with congenital isolated hypogonadotropic hypogonadism.Eur J Endocrinol. 2011 Jul;165(1):145-50. doi: 10.1530/EJE-11-0199. Epub 2011 May 4.
14	Lack of association between MAGEL2 and schizophrenia and mood disorders in the Japanese population.Neuromolecular Med. 2010 Sep;12(3):285-91. doi: 10.1007/s12017-010-8116-8. Epub 2010 May 14.
15	Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults.Nat Commun. 2016 Mar 14;7:10943. doi: 10.1038/ncomms10943.
16	A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression.Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):10008-13. doi: 10.1073/pnas.1737765100. Epub 2003 Aug 11.
17	Cancer/testis antigens: structural and immunobiological properties.Cancer Invest. 2002;20(2):222-36. doi: 10.1081/cnv-120001150.
18	Putative tumour suppressor gene necdin is hypermethylated and mutated in human cancer.Br J Cancer. 2013 Apr 2;108(6):1368-77. doi: 10.1038/bjc.2013.104.
19	Necdin modulates leukemia-initiating cell quiescence and chemotherapy response.Oncotarget. 2017 Sep 18;8(50):87607-87622. doi: 10.18632/oncotarget.20999. eCollection 2017 Oct 20.
20	Neural stem cell-like gene expression in a mouse ependymoma cell line transformed by human BK polyomavirus.Cancer Sci. 2011 Jan;102(1):122-9. doi: 10.1111/j.1349-7006.2010.01775.x. Epub 2010 Nov 12.
21	The Prader-Willi syndrome proteins MAGEL2 and necdin regulate leptin receptor cell surface abundance through ubiquitination pathways.Hum Mol Genet. 2017 Nov 1;26(21):4215-4230. doi: 10.1093/hmg/ddx311.
22	MECP2 mutations in Rett syndrome adversely affect lymphocyte growth, but do not affect imprinted gene expression in blood or brain.Hum Genet. 2002 Jun;110(6):545-52. doi: 10.1007/s00439-002-0724-4. Epub 2002 Apr 25.
23	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.
24	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.
25	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.
26	Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
27	Necdin and E2F4 are modulated by rosiglitazone therapy in diabetic human adipose and muscle tissue. Diabetes. 2006 Mar;55(3):640-50. doi: 10.2337/diabetes.55.03.06.db05-1015.
28	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.
29	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
30	Bisphenol A-associated epigenomic changes in prepubescent girls: a cross-sectional study in Gharbiah, Egypt. Environ Health. 2013 Apr 16;12:33. doi: 10.1186/1476-069X-12-33.