Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN6U6V0)

DOT Name Menin (MEN1)
Gene Name MEN1
Related Disease
Hereditary neoplastic syndrome ( )
Multiple endocrine neoplasia type 1 ( )
Ovarian neoplasm ( )
Von hippel-lindau disease ( )
Acromegaly ( )
Adrenal adenoma ( )
Adrenal gland neoplasm ( )
Anxiety ( )
Breast cancer ( )
Breast carcinoma ( )
Carney complex ( )
Colonic neoplasm ( )
Endocrine disease ( )
Familial hyperinsulinism ( )
Familial primary hyperparathyroidism ( )
Gastrinoma ( )
Hepatocellular carcinoma ( )
Hyperinsulinemic hypoglycemia ( )
Hyperparathyroidism ( )
Lung carcinoid tumor ( )
Medullary thyroid gland carcinoma ( )
Meningioma ( )
Multiple endocrine neoplasia ( )
Multiple endocrine neoplasia type 2 ( )
Multiple endocrine neoplasia type 2A ( )
Neuroendocrine cancer ( )
Osteoporosis ( )
Pheochromocytoma ( )
Pituitary tumor ( )
Trichohepatoenteric syndrome ( )
Adrenocortical carcinoma ( )
Hereditary pheochromocytoma-paraganglioma ( )
Hypercalcaemia ( )
Lung cancer ( )
Lung carcinoma ( )
Pancreatic endocrine carcinoma ( )
Paraganglioma ( )
Familial isolated hyperparathyroidism ( )
Pituitary gigantism ( )
Carcinoma ( )
Glucagonoma ( )
Hyperparathyroidism 2 with jaw tumors ( )
Hypoglycemia ( )
leukaemia ( )
Leukemia ( )
Melanoma ( )
UniProt ID
MEN1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
3U84 ; 3U85 ; 3U86 ; 3U88 ; 4GPQ ; 4GQ3 ; 4GQ4 ; 4GQ6 ; 4I80 ; 4OG3 ; 4OG4 ; 4OG5 ; 4OG6 ; 4OG7 ; 4OG8 ; 4X5Y ; 4X5Z ; 5DB0 ; 5DB1 ; 5DB2 ; 5DB3 ; 5DD9 ; 5DDA ; 5DDB ; 5DDC ; 5DDD ; 5DDE ; 5DDF ; 6B41 ; 6BXH ; 6BXY ; 6BY8 ; 6E1A ; 6O5I ; 6OPJ ; 6PKC ; 6S2K ; 6WNH ; 7M4T ; 7O9T ; 7O9X ; 7O9Z ; 7OA9 ; 7UJ4 ; 8E90 ; 8GPN ; 8IG0
Pfam ID
PF05053
Sequence
MGLKAAQKTLFPLRSIDDVVRLFAAELGREEPDLVLLSLVLGFVEHFLAVNRVIPTNVPE
LTFQPSPAPDPPGGLTYFPVADLSIIAALYARFTAQIRGAVDLSLYPREGGVSSRELVKK
VSDVIWNSLSRSYFKDRAHIQSLFSFITGTKLDSSGVAFAVVGACQALGLRDVHLALSED
HAWVVFGPNGEQTAEVTWHGKGNEDRRGQTVNAGVAERSWLYLKGSYMRCDRKMEVAFMV
CAINPSIDLHTDSLELLQLQQKLLWLLYDLGHLERYPMALGNLADLEELEPTPGRPDPLT
LYHKGIASAKTYYRDEHIYPYMYLAGYHCRNRNVREALQAWADTATVIQDYNYCREDEEI
YKEFFEVANDVIPNLLKEAASLLEAGEERPGEQSQGTQSQGSALQDPECFAHLLRFYDGI
CKWEEGSPTPVLHVGWATFLVQSLGRFEGQVRQKVRIVSREAEAAEAEEPWGEEAREGRR
RGPRRESKPEEPPPPKKPALDKGLGTGQGAVSGPPRKPPGTVAGTARGPEGGSTAQVPAP
TASPPPEGPVLTFQSEKMKGMKELLVATKINSSAIKLQLTAQSQVQMKKQKVSTPSDYTL
SFLKRQRKGL
Function
Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression. May be involved in DNA repair.
Tissue Specificity Ubiquitous.
KEGG Pathway
Cushing syndrome (hsa04934 )
Transcriptio.l misregulation in cancer (hsa05202 )
Reactome Pathway
SMAD2/SMAD3 (R-HSA-2173796 )
Deactivation of the beta-catenin transactivating complex (R-HSA-3769402 )
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426 )
RHO GTPases activate IQGAPs (R-HSA-5626467 )
Post-translational protein phosphorylation (R-HSA-8957275 )
Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755 )
Formation of the beta-catenin (R-HSA-201722 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hereditary neoplastic syndrome DISGXLG5 Definitive Genetic Variation [1]
Multiple endocrine neoplasia type 1 DIS0RJRK Definitive Autosomal dominant [2]
Ovarian neoplasm DISEAFTY Definitive Biomarker [3]
Von hippel-lindau disease DIS6ZFQQ Definitive Biomarker [4]
Acromegaly DISCC73U Strong Genetic Variation [5]
Adrenal adenoma DISC2UN8 Strong Biomarker [6]
Adrenal gland neoplasm DISFK7RF Strong Biomarker [7]
Anxiety DISIJDBA Strong Genetic Variation [8]
Breast cancer DIS7DPX1 Strong Altered Expression [9]
Breast carcinoma DIS2UE88 Strong Altered Expression [9]
Carney complex DISVL3IP Strong Biomarker [10]
Colonic neoplasm DISSZ04P Strong ModifyingMutation [11]
Endocrine disease DISRGY2N Strong Genetic Variation [12]
Familial hyperinsulinism DISHQKQE Strong Genetic Variation [13]
Familial primary hyperparathyroidism DIS6NA55 Strong Genetic Variation [14]
Gastrinoma DIS4IMNF Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
Hyperinsulinemic hypoglycemia DIS3KP5D Strong Genetic Variation [13]
Hyperparathyroidism DIS4FVAT Strong Genetic Variation [17]
Lung carcinoid tumor DISH3GHR Strong Genetic Variation [18]
Medullary thyroid gland carcinoma DISHBL3K Strong Altered Expression [19]
Meningioma DISPT4TG Strong Biomarker [20]
Multiple endocrine neoplasia DISZGBKW Strong Biomarker [21]
Multiple endocrine neoplasia type 2 DISPQ4Y5 Strong Biomarker [21]
Multiple endocrine neoplasia type 2A DIS7D3W2 Strong Genetic Variation [22]
Neuroendocrine cancer DISVGJET Strong Biomarker [23]
Osteoporosis DISF2JE0 Strong Biomarker [24]
Pheochromocytoma DIS56IFV Strong Biomarker [25]
Pituitary tumor DISN67JD Strong Genetic Variation [26]
Trichohepatoenteric syndrome DISL3ODF Strong Genetic Variation [27]
Adrenocortical carcinoma DISZF4HX moderate Biomarker [28]
Hereditary pheochromocytoma-paraganglioma DISP9K7L moderate Biomarker [29]
Hypercalcaemia DISKQ2K7 moderate Biomarker [30]
Lung cancer DISCM4YA moderate Altered Expression [31]
Lung carcinoma DISTR26C moderate Altered Expression [31]
Pancreatic endocrine carcinoma DISYZ23O moderate Genetic Variation [32]
Paraganglioma DIS2XXH5 moderate Biomarker [33]
Familial isolated hyperparathyroidism DISC2Y84 Supportive Autosomal dominant [34]
Pituitary gigantism DISIUHNT Supportive Autosomal dominant [35]
Carcinoma DISH9F1N Limited Genetic Variation [36]
Glucagonoma DISDU90K Limited Biomarker [37]
Hyperparathyroidism 2 with jaw tumors DISWEGI1 Limited Biomarker [38]
Hypoglycemia DISRCKR7 Limited Genetic Variation [39]
leukaemia DISS7D1V Limited Biomarker [40]
Leukemia DISNAKFL Limited Biomarker [40]
Melanoma DIS1RRCY Limited Biomarker [41]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) 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 Menin (MEN1). [42]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Menin (MEN1). [47]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Menin (MEN1). [50]
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8 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 Menin (MEN1). [43]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Menin (MEN1). [44]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Menin (MEN1). [45]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Menin (MEN1). [46]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Menin (MEN1). [48]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Menin (MEN1). [49]
geraniol DMS3CBD Investigative geraniol increases the expression of Menin (MEN1). [51]
AHPN DM8G6O4 Investigative AHPN decreases the expression of Menin (MEN1). [52]
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⏷ Show the Full List of 8 Drug(s)

References

1 Caspase 8 and menin expressions are not correlated in human parathyroid tumors.Endocr J. 2010;57(9):825-32. doi: 10.1507/endocrj.k10e-085. Epub 2010 Jul 3.
2 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
3 miR-762 can negatively regulate menin in ovarian cancer.Onco Targets Ther. 2017 Apr 12;10:2127-2137. doi: 10.2147/OTT.S127872. eCollection 2017.
4 Transcriptional alterations in hereditary and sporadic nonfunctioning pancreatic neuroendocrine tumors according to genotype.Cancer. 2018 Feb 1;124(3):636-647. doi: 10.1002/cncr.31057. Epub 2017 Nov 17.
5 Three Novel MEN1 Variants in AIP-Negative Familial Isolated Pituitary Adenoma Patients.Pathobiology. 2019;86(2-3):128-134. doi: 10.1159/000495252. Epub 2019 Jan 10.
6 Multiple endocrine neoplasias: advances and challenges for the future.J Intern Med. 2009 Jul;266(1):1-4. doi: 10.1111/j.1365-2796.2009.02108.x.
7 Differential expression of menin in various adrenal tumors. The role of menin in adrenal tumors.Cancer. 2001 Sep 15;92(6):1393-401. doi: 10.1002/1097-0142(20010915)92:6<1393::aid-cncr1462>3.0.co;2-4.
8 Role of multiple endocrine neoplasia type 1 mutational analysis in clinical practice.Endocr Pract. 2011 Jul-Aug;17 Suppl 3:8-17. doi: 10.4158/EP10379.RA.
9 Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A.Oncology. 2019;96(3):147-155. doi: 10.1159/000493348. Epub 2018 Oct 3.
10 Screening for genetic causes of growth hormone hypersecretion.Growth Horm IGF Res. 2016 Oct-Dec;30-31:52-57. doi: 10.1016/j.ghir.2016.10.004. Epub 2016 Oct 12.
11 Reduction of menin expression enhances cell proliferation and is tumorigenic in intestinal epithelial cells.J Biol Chem. 2004 Jun 4;279(23):24477-84. doi: 10.1074/jbc.M401835200. Epub 2004 Mar 30.
12 Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1).Hum Mutat. 2010 Jan;31(1):E1089-101. doi: 10.1002/humu.21170.
13 Multiple Endocrine Neoplasia Type 1 Presenting as Hypoglycemia due to Insulinoma.J Korean Med Sci. 2016 Jun;31(6):1003-6. doi: 10.3346/jkms.2016.31.6.1003. Epub 2016 Apr 11.
14 Frequent germ-line mutations of the MEN1, CASR, and HRPT2/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism.Horm Cancer. 2012 Apr;3(1-2):44-51. doi: 10.1007/s12672-011-0100-8.
15 Contemporary surgical management of the Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1.Best Pract Res Clin Endocrinol Metab. 2019 Oct;33(5):101318. doi: 10.1016/j.beem.2019.101318. Epub 2019 Aug 31.
16 Pharmacologic Inhibition of the Menin-MLL Interaction Leads to Transcriptional Repression of PEG10 and Blocks Hepatocellular Carcinoma.Mol Cancer Ther. 2018 Jan;17(1):26-38. doi: 10.1158/1535-7163.MCT-17-0580. Epub 2017 Nov 15.
17 Perioperative Hypotensive Crisis in an Adolescent with a Pancreatic VIPoma and MEN1-Gene Variant.Horm Res Paediatr. 2019;91(4):285-289. doi: 10.1159/000493396. Epub 2018 Oct 16.
18 Localization of the multiple endocrine neoplasia type I (MEN1) gene based on tumor loss of heterozygosity analysis.Cancer Res. 1997 May 15;57(10):1855-8.
19 Familial and Hereditary Forms of Primary Hyperparathyroidism.Front Horm Res. 2019;51:40-51. doi: 10.1159/000491037. Epub 2018 Nov 19.
20 Cytoplasmic overexpression of RNA-binding protein HuR is a marker of poor prognosis in meningioma, and HuR knockdown decreases meningioma cell growth and resistance to hypoxia.J Pathol. 2017 Aug;242(4):421-434. doi: 10.1002/path.4916. Epub 2017 Jul 5.
21 CT- and ultrasound-characteristics of hepatic lesions in patients with multiple endocrine neoplasia syndrome. A retrospective image review of 25 cases.PLoS One. 2019 Feb 28;14(2):e0212865. doi: 10.1371/journal.pone.0212865. eCollection 2019.
22 The genetics of neuroendocrine tumors.Semin Oncol. 2013 Feb;40(1):37-44. doi: 10.1053/j.seminoncol.2012.11.005.
23 Two well-differentiated pancreatic neuroendocrine tumor mouse models.Cell Death Differ. 2020 Jan;27(1):269-283. doi: 10.1038/s41418-019-0355-0. Epub 2019 Jun 3.
24 Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis.Cell Death Differ. 2017 Apr;24(4):672-682. doi: 10.1038/cdd.2016.165. Epub 2017 Jan 20.
25 First report of concomitant pheochromocytoma and duodenal neuroendocrine tumour in a sporadic multiple endocrine neoplasia type 1.BMJ Case Rep. 2018 Sep 4;2018:bcr2017222947. doi: 10.1136/bcr-2017-222947.
26 Loss of heterozygosity of the MEN1 gene in a large series of TSH-secreting pituitary adenomas.J Endocrinol Invest. 2001 Nov;24(10):796-801. doi: 10.1007/BF03343929.
27 Multiple endocrine neoplasia type 1 in Poland: a two-centre experience.Endokrynol Pol. 2019;70(5):385-391. doi: 10.5603/EP.a2019.0031. Epub 2019 Jul 5.
28 Integrated genomic characterization of adrenocortical carcinoma.Nat Genet. 2014 Jun;46(6):607-12. doi: 10.1038/ng.2953. Epub 2014 Apr 20.
29 Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.J Clin Endocrinol Metab. 2015 Mar;100(3):E531-41. doi: 10.1210/jc.2014-3399. Epub 2014 Dec 12.
30 Parental Multiple Endocrine Neoplasia Type 1 (MEN 1) Is Associated with Increased Offspring Childhood Mortality.J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz231. doi: 10.1210/clinem/dgz231.
31 miR?4 may be a negative regulator of menin in lung cancer.Oncol Rep. 2018 May;39(5):2342-2350. doi: 10.3892/or.2018.6327. Epub 2018 Mar 20.
32 Pancreatic neuroendocrine carcinomas reveal a closer relationship to ductal adenocarcinomas than to neuroendocrine tumors G3.Hum Pathol. 2018 Jul;77:70-79. doi: 10.1016/j.humpath.2018.03.018. Epub 2018 Mar 26.
33 MEN1-associated primary hyperparathyroidism in the Spanish Registry: clinical characterictics and surgical outcomes.Endocr Connect. 2019 Oct;8(10):1416-1424. doi: 10.1530/EC-19-0321.
34 A family with isolated hyperparathyroidism segregating a missense MEN1 mutation and showing loss of the wild-type alleles in the parathyroid tumors. Am J Hum Genet. 1998 Nov;63(5):1544-9. doi: 10.1086/302097.
35 Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocr Relat Cancer. 2015 Oct;22(5):745-57. doi: 10.1530/ERC-15-0320. Epub 2015 Jul 17.
36 Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin-remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D.J Pathol. 2017 Mar;241(4):488-500. doi: 10.1002/path.4853. Epub 2016 Dec 29.
37 Foxa2, a novel protein partner of the tumour suppressor menin, is deregulated in mouse and human MEN1 glucagonomas.J Pathol. 2017 May;242(1):90-101. doi: 10.1002/path.4885. Epub 2017 Mar 27.
38 Molecular genetics of syndromic and non-syndromic forms of parathyroid carcinoma.Hum Mutat. 2017 Dec;38(12):1621-1648. doi: 10.1002/humu.23337. Epub 2017 Sep 25.
39 Creating a patient carried Men1 gene point mutation on wild type iPSCs locus mediated by CRISPR/Cas9 and ssODN.Stem Cell Res. 2017 Jan;18:67-69. doi: 10.1016/j.scr.2016.12.007. Epub 2016 Dec 9.
40 Distinct pathways affected by menin versus MLL1/MLL2 in MLL-rearranged acute myeloid leukemia.Exp Hematol. 2019 Jan;69:37-42. doi: 10.1016/j.exphem.2018.10.001. Epub 2018 Oct 10.
41 Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation in a family with atypical tumor phenotype.Hormones (Athens). 2016 Jan-Mar;15(1):113-7. doi: 10.14310/horm.2002.1626.
42 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.
43 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
44 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
45 Molecular analysis of MEN1 expression in MCF7, T47D and MDA-MB 468 breast cancer cell lines treated with adriamycin using RT-PCR and immunocytochemistry. Daru. 2010;18(1):17-22.
46 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
47 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.
48 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
49 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.
50 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
51 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
52 ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.