Affinage

MEN1

Menin · UniProt O00255

Length
610 aa
Mass
67.5 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Menin, encoded by MEN1, is a predominantly nuclear scaffold protein that acts as a tumor suppressor by coordinating chromatin-based transcriptional control with cell cycle restraint, and its inactivation drives neuroendocrine tumorigenesis (PMID:9465067, PMID:21252315). It restrains the G0/G1-to-S transition by maintaining expression of the CDK inhibitors p18(Ink4c) and p27(Kip1); loss of menin elevates CDK2 activity and accelerates S-phase entry, and complementation with wild-type menin reverses this (PMID:16740708). Genetic epistasis establishes that p18(Ink4c) and menin act in the same pathway to suppress neuroendocrine and lung tumors through control of Rb phosphorylation, with CDK4 — not CDK2 — being the kinase required for MEN1-dependent pituitary and islet tumorigenesis (PMID:17145768, PMID:17409423, PMID:24531709); menin and Rb likewise operate in a shared, lineage-specific pathway (PMID:17893233). Menin enforces transcriptional programs through chromatin: it recruits PRMT5 to target promoters such as Gas1 to deposit repressive H4R3me2s marks and suppress Hedgehog signaling, and disease-associated menin mutants fail to bind PRMT5 or impose this mark (PMID:23580576, PMID:35835391); it also represses JunD-mediated transcription, a function conserved to zebrafish (PMID:10818209). Within the MLL1 histone H3K4 methyltransferase complex, menin maintains normal chromatin occupancy, and its loss redistributes MLL1 to repetitive elements, raising H3K4me3 there, inducing double-stranded RNA expression and immune infiltration, such that menin-MLL inhibition restrains tumors in a CD8+ T cell-dependent manner (PMID:39227744). Menin loss also restrains differentiated-cell plasticity, permitting transdifferentiation of pancreatic alpha cells into insulinoma cells and reprogramming of glial cells toward neuroendocrine fates (PMID:20138042, PMID:35835391). Menin protein abundance is set post-translationally by CUL4B-DCAF7-mediated, neddylation-dependent ubiquitination and proteasomal degradation, and is stabilized in response to tissue injury (PMID:32156729, PMID:36939378). Inactivating somatic MEN1 mutations and a 5'UTR/core-promoter deletion that collapses menin expression underlie pancreatic neuroendocrine and MEN1-related tumors (PMID:21252315, PMID:32780883), and clinical resistance to menin inhibitors arises from mutations at the menin-MLL1 drug interface that block inhibitor-induced eviction of menin and MLL1 from chromatin without disrupting the native MLL1 interaction (PMID:36922589).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    Established where menin acts in the cell, defining it as a nuclear protein with discrete C-terminal localization signals — a prerequisite for any chromatin/transcriptional model.

    Evidence Immunofluorescence, subcellular fractionation, and GFP deletion mapping

    PMID:9465067

    Open questions at the time
    • Does not define molecular activity or binding partners
    • NLS mapping does not address cytoplasmic functions later reported
  2. 2000 Medium

    Identified a conserved transcriptional output for menin by showing it binds JunD and represses JunD-driven transcription, the first specific mechanistic activity assigned.

    Evidence Protein binding and reporter assays in a zebrafish ortholog system

    PMID:10818209

    Open questions at the time
    • Ortholog/reporter system, not endogenous human loci
    • Does not establish how JunD repression links to tumor suppression
  3. 2006 High

    Connected menin loss to cell cycle deregulation, showing it maintains CDK inhibitors p18/p27 to restrain S-phase entry, providing a proliferative mechanism for tumor suppression.

    Evidence Conditional Men1 knockout in MEFs and islets with cell cycle, CDK2, and rescue analyses

    PMID:16740708

    Open questions at the time
    • Does not resolve which downstream CDK is rate-limiting in vivo
    • Mechanism by which menin maintains p18/p27 transcription not defined here
  4. 2006 High

    Pinpointed p18(Ink4c) as the genetically relevant collaborator with menin in the same Rb pathway, distinguishing it from p27 in neuroendocrine tumor suppression.

    Evidence Double-mutant mouse epistasis, Rb phosphorylation, and LOH analysis

    PMID:17145768

    Open questions at the time
    • Tissue specificity of p18 vs p27 contribution not fully explained
    • Does not identify the CDK enforcing the Rb phenotype
  5. 2007 High

    Extended the menin-p18 collaboration to lung stem cell expansion and NSCLC, showing the pathway operates beyond endocrine tissues.

    Evidence p18(-/-);Men1(+/-) mouse lung tumor model with stem cell quantification and Rb phosphorylation

    PMID:17409423

    Open questions at the time
    • Does not define menin's molecular role in stem cell compartment
    • Relative contribution of CDK2 vs CDK4/6 sites not resolved
  6. 2007 Medium

    Placed Men1 and Rb in the same pathway via mutually exclusive allele loss and revealed lineage-specific consequences of menin loss.

    Evidence Men1;Rb compound mouse model, LOH, phospho-Rb, and RNAi in tumor cells

    PMID:17893233

    Open questions at the time
    • Mechanism of cell-lineage-specific apoptosis on Men1 knockdown unclear
    • Single lab
  7. 2010 High

    Demonstrated that menin restrains differentiated cell plasticity, with its loss permitting alpha-to-beta cell transdifferentiation into insulinoma — a fate-control rather than purely proliferative role.

    Evidence Alpha cell-specific Men1 knockout with genetic lineage tracing

    PMID:20138042

    Open questions at the time
    • Molecular mediators of the transdifferentiation not identified
    • Does not link fate change to specific menin chromatin targets
  8. 2011 Medium

    Established the clinical and biological weight of MEN1 loss by showing somatic inactivating mutations in ~44% of PanNETs and framing menin as a chromatin/HMT-complex component.

    Evidence Exome sequencing of 68 pancreatic neuroendocrine tumors

    PMID:21252315

    Open questions at the time
    • Sequencing alone does not demonstrate mechanism
    • Does not show which chromatin function is lost in tumors
  9. 2013 High

    Defined a direct epigenetic-repressive mechanism: menin recruits PRMT5 to deposit H4R3me2s and silence Hedgehog target Gas1, with disease mutants failing this — linking chromatin marks to a tumorigenic pathway.

    Evidence Reciprocal Co-IP, ChIP, reporter assays, mutant binding, and pharmacologic Hedgehog inhibition in MEN1 tumors

    PMID:23580576

    Open questions at the time
    • Genome-wide extent of PRMT5 recruitment not mapped
    • Relationship between PRMT5 and MLL1 complexes not resolved
  10. 2014 High

    Resolved which CDK is rate-limiting, showing CDK4 (not CDK2) is required for MEN1-dependent pituitary and islet tumorigenesis, refining therapeutic targeting downstream of menin.

    Evidence Men1;Cdk4 and Men1;Cdk2 double-mutant mice plus CDK knockdown in insulinoma cells with phospho-RB readout

    PMID:24531709

    Open questions at the time
    • Does not reconcile with earlier CDK2 activity findings across tissues
    • Mechanism connecting menin loss to CDK4 activation not defined
  11. 2016 Medium

    Proposed a DNA-methylation arm of menin tumor suppression, where loss activates DNMT1 via Rbbp5, causing hypermethylation that silences Sox genes and activates Wnt/beta-catenin.

    Evidence Genome-wide methylation analysis in MEN1 tumors, Men1 KO mice and MEFs, DNMT1 activity assays

    PMID:26871472

    Open questions at the time
    • Single lab; mechanism of Rbbp5-DNMT1 activation needs orthogonal validation
    • Causal link between hypermethylation and Wnt activation not fully established
  12. 2020 High

    Showed menin governs exocrine pancreas injury response and regeneration partly via JunD target restraint, and cooperates with mutant Kras in oncogenesis, with menin protein stabilized upon insult.

    Evidence Conditional Men1 KO with caerulein pancreatitis, KrasG12D compound model, and protein stability assay

    PMID:32156729

    Open questions at the time
    • How injury stabilizes menin protein not mechanistically defined
    • Direct JunD target set in exocrine pancreas not enumerated
  13. 2020 Medium

    Revealed that menin loss antagonizes Kras-induced senescence and EMT and drives neuroendocrine differentiation of lung cancer, with DNA damage accumulation.

    Evidence ATII KrasG12D/Men1-/- mouse model with DNA damage, senescence, EMT and NE marker analysis

    PMID:32081882

    Open questions at the time
    • Molecular mechanism linking menin loss to NE reprogramming not defined
    • Single lab
  14. 2020 Medium

    Demonstrated that the MEN1 5'UTR/core promoter is required for menin expression, identifying a regulatory cause of menin loss beyond coding mutations.

    Evidence Luciferase reporter, qRT-PCR, and Western blotting in patient-derived lymphoblastoid cells

    PMID:32780883

    Open questions at the time
    • Transcription factors acting at this promoter not identified
    • Single patient-derived deletion characterized
  15. 2022 Medium

    Identified a metabolic tumor-suppressive function in which menin promotes ferroptosis by inhibiting the mTOR-SCD1 axis in pNET cells.

    Evidence Metabolomics, MEN1 gain/loss, mTOR/SCD1 readouts, lipid peroxidation, and oleic acid/everolimus rescue

    PMID:36604142

    Open questions at the time
    • How nuclear menin suppresses mTOR mechanistically unclear
    • Single lab
  16. 2022 Medium

    Showed menin loss reprograms glial cells toward neuroendocrine fates via downstream Hedgehog signaling, linking fate control to the PRMT5/Hedgehog axis.

    Evidence GFAP-Cre Men1 KO with lineage tracing and Kif3a/Sox10 genetic epistasis

    PMID:35835391

    Open questions at the time
    • Direct chromatin targets driving reprogramming not mapped
    • Single lab
  17. 2023 High

    Defined the post-translational control of menin abundance, identifying CUL4B-DCAF7 as the E3 machinery and neddylation as required for its degradation.

    Evidence Reciprocal Co-IP, in vitro ubiquitination, RNAi, MLN4924, and in vivo genetic rescue

    PMID:36939378

    Open questions at the time
    • Signals triggering DCAF7-mediated degradation not defined
    • Site(s) of menin ubiquitination not mapped
  18. 2023 High

    Explained clinical menin-inhibitor resistance, showing mutations at the menin-MLL1 drug interface block inhibitor-induced chromatin eviction without disrupting the native interaction.

    Evidence Clinical resistance sequencing, xenografts, base-editor screen, structural and ChIP analysis

    PMID:36922589

    Open questions at the time
    • Strategies to overcome interface resistance not established
    • Does not address resistance arising outside the interface
  19. 2024 High

    Uncovered a tumor microenvironment-dependent function: menin loss redistributes MLL1, activates dsRNA/immune responses, and renders tumors sensitive to menin-MLL inhibition via CD8+ T cells.

    Evidence In vivo CRISPR screen, H3K4me3 ChIP-seq, dsRNA and immune profiling, and immune-competent vs depleted mouse models

    PMID:39227744

    Open questions at the time
    • Mechanism restraining MLL1 redistribution by menin not detailed
    • Generalizability across tumor types not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How menin's distinct nuclear activities — MLL1 H3K4 methylation, PRMT5 recruitment, JunD repression, and DNMT1 regulation — are integrated on chromatin, and how these connect to cytoplasmic mTOR/ferroptosis control, remains unresolved.
  • No unified model linking menin's repressive and activating chromatin functions
  • Mechanism by which a nuclear scaffold modulates mTOR signaling unclear
  • Cell-type determinants of menin's opposing roles not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005654 nucleoplasm 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-392499 Metabolism of proteins 1
Partners
CUL4BDCAF7JUNDMLL1PRMT5RBBP5
Complex memberships
CUL4B-DCAF7 E3 ubiquitin ligase complexMLL1 H3K4 methyltransferase complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Menin is located primarily in the nucleus, with at least two independent nuclear localization signals (NLS) both located in the C-terminal fourth of the protein, as determined by immunofluorescence, subcellular fractionation Western blotting, and GFP-tagging of deletion constructs. Immunofluorescence, Western blotting of subcellular fractions, epitope-tagged GFP deletion constructs Proceedings of the National Academy of Sciences of the United States of America High 9465067
2000 Zebrafish menin binds both human and mouse JunD and represses JunD-induced transcription, demonstrating that the JunD-binding and transcriptional repression function of menin is evolutionarily conserved. Protein binding assay, transcriptional reporter assay in zebrafish Mammalian genome : official journal of the International Mammalian Genome Society Medium 10818209
2006 Men1 excision in mouse embryonic fibroblasts accelerates G0/G1 to S phase entry, accompanied by increased CDK2 activity and decreased expression of CDK inhibitors p18(Ink4c) and p27(Kip1). Complementation with wild-type menin represses S-phase entry. In vivo, Men1 excision in pancreatic islets increases proliferation within 7 days. Conditional Men1 knockout in MEFs (Cre-lox), cell cycle analysis, CDK2 kinase assay, in vivo tamoxifen-inducible Men1 deletion in pancreatic islets with BrdU labeling Cancer research High 16740708
2006 Genetic epistasis in mice shows that p18(Ink4c), but not p27(Kip1), functionally collaborates with Men1 to suppress neuroendocrine organ tumors. p18(-/-);Men1(+/-) mice develop tumors at accelerated rates with increased Rb phosphorylation at both CDK2 and CDK4/6 sites, and the remaining wild-type Men1 allele is often retained in p18-null compound tumors, indicating functional redundancy between p18 and Men1 in the same pathway. Double-mutant mouse epistasis, tumor incidence analysis, Rb phosphorylation western blotting, LOH analysis Molecular and cellular biology High 17145768
2007 p18(Ink4c) functionally collaborates with Men1 to constrain lung stem cell expansion and suppress non-small-cell lung cancers; bronchioalveolar stem cells are further expanded in p18(-/-);Men1(+/-) compound mice compared to single mutants, and Rb phosphorylation at CDK2 and CDK4/CDK6 sites is significantly increased. Double-mutant mouse model, lung tumor characterization, Rb phosphorylation analysis, bronchioalveolar stem cell quantification Cancer research High 17409423
2013 Menin directly interacts with PRMT5, a negative regulator of gene transcription. Menin recruits PRMT5 to the Gas1 gene promoter, increases repressive histone arginine symmetric dimethylation (H4R3m2s), and suppresses Gas1 expression, thereby epigenetically suppressing Hedgehog signaling. MEN1 disease-related menin mutants show reduced PRMT5 binding and fail to impart the H4R3m2s mark at the Gas1 promoter. Co-immunoprecipitation, ChIP assay, histone methylation analysis, luciferase reporter, pharmacologic Hedgehog inhibition in MEN1 mouse tumors, mutant menin binding analysis Cancer research High 23580576
2014 CDK4, but not CDK2, is required for MEN1-dependent tumorigenesis in pituitary and pancreatic islets. Men1(+/-);Cdk4(-/-) mice do not develop tumors and remain hypoplastic, while Men1(+/-);Cdk2(-/-) mice show normal tumorigenesis. CDK4 knockdown in INS-1 insulinoma cells inhibits glucose-stimulated cell cycle progression with decreased RB phosphorylation at Ser780, while CDK2 knockdown has minimal effect. Double-mutant mouse epistasis, tumor incidence analysis, LOH analysis, CDK4/CDK2 knockdown in insulinoma cells, RB phosphorylation western blotting Oncogene High 24531709
2010 Alpha cell-specific Men1 ablation in mice leads to the transdifferentiation of glucagon-expressing cells into insulinoma cells, demonstrating that menin regulates the plasticity of differentiated pancreatic alpha cells in vivo. Genetic cell lineage tracing confirmed that insulinoma cells were directly derived from glucagon-expressing cells. Conditional Men1 knockout (GluCre-loxP), genetic cell lineage tracing, immunohistochemistry, transcription factor expression analysis Gastroenterology High 20138042
2016 Loss of menin activates DNMT1 by activating retinoblastoma-binding protein 5 (Rbbp5), leading to global DNA hypermethylation. This aberrant methylation inactivates Sox regulatory genes and aberrantly activates Wnt/β-catenin signaling. Demonstrated in MEN1 parathyroid tumors, Men1 knockout mice, and Men1-null MEF cell lines. Genome-wide methylation analysis, Men1 KO mouse and MEF cell lines, DNMT1 activity assay, Rbbp5 pathway analysis Oncotarget Medium 26871472
2020 Men1 loss in the exocrine pancreas causes increased injury and impaired regeneration following acute caerulein-induced pancreatitis. Men1 protein is stabilized in response to pancreatic insult. Loss of Men1 is associated with overexpression of pro-inflammatory JunD target genes, suggesting menin suppresses JunD activity in the exocrine pancreas. Men1 loss also significantly accelerates mutant Kras-dependent pancreatic oncogenesis. Conditional Men1 KO mouse model, caerulein pancreatitis model, KrasG12D compound mouse model, Men1 protein stability assay, JunD target gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 32156729
2023 Somatic mutations at the menin-MLL1 interface (revumenib-menin interface) confer clinical resistance to menin inhibition. These mutations attenuate drug-target binding via structural perturbations that impact small-molecule binding but not the natural MLL1 interaction, and prevent inhibitor-induced eviction of menin and MLL1 from chromatin. Clinical resistance mutation sequencing, xenograft models, base-editor screen, structural perturbation analysis, chromatin immunoprecipitation Nature High 36922589
2023 MEN1 protein is degraded via the neddylation pathway and CUL4B-DCAF7-mediated ubiquitination. DCAF7 binds menin and catalyzes its ubiquitination, leading to proteasomal degradation. Suppression of neddylation (MLN4924) or DCAF7 knockdown induces MEN1 accumulation, and the oncogenic effects of DCAF7 loss are counteracted by simultaneous MEN1 knockdown. Co-immunoprecipitation, ubiquitination assay, RNAi knockdown, neddylation inhibitor (MLN4924), in vitro and in vivo rescue experiments Cancer research High 36939378
2024 MEN1 knockout redistributes MLL1 chromatin occupancy, increasing H3K4me3 at repetitive genomic regions, activating double-stranded RNA expression, and increasing immune cell infiltration. Pharmacological inhibition of the menin-MLL interaction reduces tumor growth in a CD8+ T cell-dependent manner, revealing a tumor microenvironment-dependent function of MEN1. In vivo CRISPR-Cas9 screen in xenograft vs. 2D culture, ChIP-seq (H3K4me3), dsRNA expression analysis, immune cell profiling, pharmacologic menin-MLL inhibition in immunocompetent and immunodeficient mice, CD8+ T cell depletion Nature genetics High 39227744
2011 MEN1, encoding menin, is a component of a histone methyltransferase complex; 44% of pancreatic neuroendocrine tumors carry somatic inactivating mutations in MEN1, establishing menin as a chromatin remodeling factor whose loss contributes to PanNET tumorigenesis. Exome sequencing of 68 PanNETs, mutation screening Science (New York, N.Y.) Medium 21252315
2020 MEN1 deficiency in a KrasG12D lung cancer mouse model leads to accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition, resulting in neuroendocrine differentiation of lung cancer. ATII-specific KrasG12D/Men1-/- genetically engineered mouse model, DNA damage markers, senescence assays, EMT marker analysis, NE differentiation markers Nature communications Medium 32081882
2007 In Men1(+/-)Rb(+/-) compound mice, loss of the remaining wild-type Men1 and Rb alleles is mutually exclusive in all tumors, indicating that Men1 and Rb act in the same pathway. Down-regulation of Men1 targets p18 and p27 and increased phospho-Rb were observed in Men1-deficient pheochromocytomas. RNAi knockdown of Men1 increased apoptosis in Rb-deficient medullary thyroid carcinoma cells, revealing cell lineage-specific interactions. Compound mutant mouse model, LOH analysis, p18/p27 expression analysis, phospho-Rb western blot, RNAi knockdown in cell lines Carcinogenesis Medium 17893233
2022 GFAP-directed Men1 inactivation in glial cells induces neuroendocrine differentiation and tumorigenesis (pancreatic NETs, prolactinomas). Men1 deletion causes loss of glial progenitor markers and gain of neuroendocrine genes. Co-deletion of Kif3a (Hedgehog mediator) attenuates neuroendocrine hyperplasia, implicating Hedgehog signaling downstream of Men1 in glial-to-neuroendocrine reprogramming. Conditional Men1 KO (GFAP-Cre), Cre lineage tracing (tdTomato), gene expression analysis, double KO (Kif3a/Men1 and Sox10/Men1) Cellular and molecular gastroenterology and hepatology Medium 35835391
2022 Menin promotes ferroptosis in pancreatic neuroendocrine tumor cells by inhibiting the mTOR-SCD1 axis. MEN1 overexpression suppresses mTOR signaling and reduces SCD1 expression; oleic acid (an SCD1 metabolite) rescues lipid peroxidation caused by MEN1 overexpression. MEN1-overexpressing cells are more sensitive to the mTOR inhibitor everolimus. Targeted metabolomics, MEN1 overexpression/knockdown in pNET cells, mTOR pathway analysis, SCD1 expression assay, ferroptosis assays, lipid peroxidation measurement, everolimus sensitivity assay Acta biochimica et biophysica Sinica Medium 36604142
2017 MEN1/Menin suppresses the PI3K/Akt/mTOR pathway in bovine mammary epithelial cells; menin overexpression significantly suppresses mTOR pathway factors and milk protein κ-casein, while MEN1 knockdown increases them. Menin also negatively modulates responses to prolactin and insulin upstream of mTOR. MEN1 overexpression and knockdown in bovine mammary epithelial cells and tissues, mTOR pathway western blotting, milk protein (κ-casein) expression analysis Scientific reports Low 28710500
2020 A 596 bp deletion in the 5' UTR of MEN1 including the core promoter causes significant reductions (37-fold in HEK293, 16-fold in BON-1) in promoter-driven luciferase expression, and 84% and 88% reductions in MEN1 mRNA and menin protein, respectively, in patient-derived lymphoblastoid cells, establishing a regulatory role for the MEN1 5' UTR in menin expression. Luciferase reporter assay, qRT-PCR, Western blotting in patient-derived EBV-transformed lymphoblastoid cells Journal of bone and mineral research Medium 32780883

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science (New York, N.Y.) 1396 21252315
2012 Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). The Journal of clinical endocrinology and metabolism 959 22723327
1997 Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Human molecular genetics 518 9215690
2008 Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Human mutation 456 17879353
1998 Menin, the product of the MEN1 gene, is a nuclear protein. Proceedings of the National Academy of Sciences of the United States of America 357 9465067
1997 Somatic mutation of the MEN1 gene in parathyroid tumours. Nature genetics 347 9241276
2013 Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Molecular and cellular endocrinology 267 23933118
1997 Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Human molecular genetics 198 9361035
2023 MEN1 mutations mediate clinical resistance to menin inhibition. Nature 197 36922589
2003 Of mice and MEN1: Insulinomas in a conditional mouse knockout. Molecular and cellular biology 195 12917331
2018 ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup. Nature communications 178 30315258
2010 Multiple endocrine neoplasia type 1 (MEN1). Best practice & research. Clinical endocrinology & metabolism 165 20833329
2012 Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 142 22575867
2019 Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis. Frontiers in endocrinology 140 31263451
2010 MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169 sporadic neoplasms reveals alterations in the vast majority of cases. Endocrine-related cancer 131 20566584
1998 Characterization of the mouse Men1 gene and its expression during development. Oncogene 118 9824159
2004 Conditional inactivation of the MEN1 gene leads to pancreatic and pituitary tumorigenesis but does not affect normal development of these tissues. Molecular and cellular biology 114 15060136
2009 Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 109 19309299
2016 MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients. BMC medicine 108 27842554
2010 Alpha cell-specific Men1 ablation triggers the transdifferentiation of glucagon-expressing cells and insulinoma development. Gastroenterology 105 20138042
2015 Multiple endocrine neoplasia type 1 (MEN1): An update of 208 new germline variants reported in the last nine years. Cancer genetics 102 26767918
2004 Molecular pathology of the MEN1 gene. Annals of the New York Academy of Sciences 102 15153434
2006 Mutation of tumor suppressor gene Men1 acutely enhances proliferation of pancreatic islet cells. Cancer research 95 16740708
2013 Menin epigenetically represses Hedgehog signaling in MEN1 tumor syndrome. Cancer research 88 23580576
1999 MEN1 gene mutation analysis of sporadic adrenocortical lesions. International journal of cancer 77 9935177
2009 Multiple endocrine neoplasia type 1 (MEN1): not only inherited endocrine tumors. Genetics in medicine : official journal of the American College of Medical Genetics 76 19904212
1999 Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases. Human mutation 76 9888389
1999 MEN1 gene analysis in sporadic adrenocortical neoplasms. The Journal of clinical endocrinology and metabolism 75 9920087
2017 The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocrine-related cancer 66 28899949
2007 Endocrine precursor lesions and microadenomas of the duodenum and pancreas with and without MEN1: criteria, molecular concepts and clinical significance. Pathobiology : journal of immunopathology, molecular and cellular biology 62 17890894
1999 Isolation, genomic organization, and expression analysis of Men1, the murine homolog of the MEN1 gene. Mammalian genome : official journal of the International Mammalian Genome Society 58 10341092
2003 Functional studies of the MEN1 gene. Journal of internal medicine 57 12755956
2019 UMD-MEN1 Database: An Overview of the 370 MEN1 Variants Present in 1676 Patients From the French Population. The Journal of clinical endocrinology and metabolism 55 30339208
2015 MEN1, MEN4, and Carney Complex: Pathology and Molecular Genetics. Neuroendocrinology 54 25592387
2018 Current and emerging therapies for PNETs in patients with or without MEN1. Nature reviews. Endocrinology 51 29449689
2017 Genome-Wide Analysis Identifies MEN1 and MAX Mutations and a Neuroendocrine-Like Molecular Heterogeneity in Quadruple WT GIST. Molecular cancer research : MCR 51 28130400
1999 Sequence analysis and transcript expression of the MEN1 gene in sporadic pituitary tumours. British journal of cancer 50 10389976
1999 Somatic MEN1 gene mutation does not contribute significantly to sporadic pituitary tumorigenesis. European journal of endocrinology 48 10366412
2006 p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Molecular and cellular biology 47 17145768
1998 MEN1 gene mutations in 12 MEN1 families and their associated tumors. European journal of endocrinology 47 9820618
2000 MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma. Genes, chromosomes & cancer 45 10738303
2000 Identification of MEN1 gene mutations in families with MEN 1 and related disorders. British journal of cancer 45 10993647
2017 Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1. Endocrine-related cancer 43 28811299
2012 MEN1-related hyperparathyroidism: response to cinacalcet and its relationship with the calcium-sensing receptor gene variant Arg990Gly. European journal of endocrinology 42 22577108
2018 The Importance of an Early and Accurate MEN1 Diagnosis. Frontiers in endocrinology 41 30254610
2001 Characterization of a MEN1 ortholog from Drosophila melanogaster. Gene 41 11223240
2007 p18Ink4c collaborates with Men1 to constrain lung stem cell expansion and suppress non-small-cell lung cancers. Cancer research 38 17409423
1999 Studies of the murine homolog of the multiple endocrine neoplasia type 1 (MEN1) gene, men1. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38 9893060
2025 Multiple endocrine neoplasia type 1 (MEN1): recommendations and guidelines for best practice. The lancet. Diabetes & endocrinology 37 40523372
2020 MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response. Nature communications 37 32081882
2009 MEN1 gene and its mutations: basic and clinical implications. Cancer science 37 19068082
2023 MEN1 Degradation Induced by Neddylation and the CUL4B-DCAF7 Axis Promotes Pancreatic Neuroendocrine Tumor Progression. Cancer research 36 36939378
2000 MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1. European journal of endocrinology 36 10664520
2020 Phenotypes Associated With MEN1 Syndrome: A Focus on Genotype-Phenotype Correlations. Frontiers in endocrinology 35 33312161
1998 Identification and characterization of the multiple endocrine neoplasia type 1 (MEN1) gene. Journal of internal medicine 34 9681840
1998 Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN1). Journal of internal medicine 34 9681842
2000 Isolation, characterization, expression and functional analysis of the zebrafish ortholog of MEN1. Mammalian genome : official journal of the International Mammalian Genome Society 33 10818209
2016 Loss of p27 expression is associated with MEN1 gene mutations in sporadic parathyroid adenomas. Endocrine 32 27038812
2012 Variable clinical expression in patients with a germline MEN1 disease gene mutation: clues to a genotype-phenotype correlation. Clinics (Sao Paulo, Brazil) 32 22584706
2009 The MEN1 gene and pituitary tumours. Hormone research 32 19407509
2007 Cell lineage-specific interactions between Men1 and Rb in neuroendocrine neoplasia. Carcinogenesis 32 17893233
2014 MEN1 tumorigenesis in the pituitary and pancreatic islet requires Cdk4 but not Cdk2. Oncogene 31 24531709
2018 DNA methylation profiling in MEN1-related pancreatic neuroendocrine tumors reveals a potential epigenetic target for treatment. European journal of endocrinology 30 29903750
2016 Deletion of Men1 and somatostatin induces hypergastrinemia and gastric carcinoids. Gut 30 26860771
2020 Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer. Cancers 29 32937789
2002 Genetic analysis of the MEN1 gene and HPRT2 locus in two Italian kindreds with familial isolated hyperparathyroidism. Clinical endocrinology 29 11966738
1999 MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation. Pathology international 28 10594843
2021 Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs). Seminars in cancer biology 27 33905872
2007 Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. Human molecular genetics 26 17613551
1999 Characterization of the MEN1 ortholog in zebrafish. Biochemical and biophysical research communications 26 10529376
2020 Clinical MEN-1 Among a Large Cohort of Patients With Acromegaly. The Journal of clinical endocrinology and metabolism 25 32311048
2019 A somatic mutation in MEN1 gene detected in periventricular nodular heterotopia tissue obtained from depth electrodes. Epilepsia 25 31489630
2019 Adrenocortical carcinoma in patients with MEN1: a kindred report and review of the literature. Endocrine connections 24 30721134
2017 Analysis of differentially expressed microRNAs in MEN1 parathyroid adenomas. American journal of translational research 24 28469779
2019 True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome. Endocrine 23 31044390
2016 Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis. Oncotarget 23 26871472
2012 MEN1 gene replacement therapy reduces proliferation rates in a mouse model of pituitary adenomas. Cancer research 23 22915754
2009 Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition. Journal of endocrinological investigation 23 19474519
2000 Heterogeneity at the 5'-end of MEN1 transcripts. Biochemical and biophysical research communications 23 11027505
2013 A MEN1 syndrome with a paraganglioma. European journal of human genetics : EJHG 22 23778871
2012 Alterations of MEN1 and E-cadherin/β-catenin complex in sporadic pulmonary carcinoids. International journal of oncology 21 22825745
2024 In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions. Nature genetics 20 39227744
2020 Whole genome sequencing of apparently mutation-negative MEN1 patients. European journal of endocrinology 20 31658439
2017 MEN1/Menin regulates milk protein synthesis through mTOR signaling in mammary epithelial cells. Scientific reports 20 28710500
2001 The MEN1 gene and associated diseases: an update. Endocrine pathology 20 11740047
2018 Epigenetic regulation in the tumorigenesis of MEN1-associated endocrine cell types. Journal of molecular endocrinology 19 29615472
2018 Children with MEN1 gene mutations may present first (and at a young age) with Cushing disease. Clinical endocrinology 19 29927501
2017 MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism. Virchows Archiv : an international journal of pathology 19 28597079
2017 A MEN1 pancreatic neuroendocrine tumour mouse model under temporal control. Endocrine connections 18 28420716
2015 MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma. The Journal of clinical endocrinology and metabolism 18 25625803
2022 GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming. Cellular and molecular gastroenterology and hepatology 17 35835391
2019 MEN1-associated primary hyperparathyroidism in the Spanish Registry: clinical characterictics and surgical outcomes. Endocrine connections 17 31557724
2007 MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1. Clinical endocrinology 17 17953629
2004 Novel somatic MEN1 gene alterations in sporadic primary hyperparathyroidism and correlation with clinical characteristics. Journal of endocrinological investigation 17 15754732
2020 Men1 maintains exocrine pancreas homeostasis in response to inflammation and oncogenic stress. Proceedings of the National Academy of Sciences of the United States of America 16 32156729
2020 Multiple Endocrine Neoplasia Type 1 (MEN1) 5'UTR Deletion, in MEN1 Family, Decreases Menin Expression. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 32780883
2017 Animal models of MEN1. Endocrine-related cancer 16 28743793
2012 MEN1 and pituitary adenomas. Annales d'endocrinologie 16 22542456
2022 MEN1 promotes ferroptosis by inhibiting mTOR-SCD1 axis in pancreatic neuroendocrine tumors. Acta biochimica et biophysica Sinica 15 36604142
2013 Diagnosis and treatment of multiple endocrine neoplasia type 1 (MEN1). Minerva endocrinologica 15 23435440

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