{"entity":{"id":"menin","kind":"target","name":"Menin","aka":[],"tldr":"A scaffold protein that certain leukaemias need to keep their genes switched on; the first drug against it was approved in 2024.","summary":"Menin (encoded by MEN1) is a scaffold protein that links KMT2A fusion proteins to chromatin; small-molecule inhibitors displace the complex, switch off the leukaemia gene programme and let blasts differentiate. Revumenib (Revuforj) is approved for KMT2A-rearranged and NPM1-mutant acute leukaemia, and ziftomenib followed. NPM1 mutation is found in roughly 25 to 30 percent of AML and KMT2A rearrangement in about 5 to 10 percent, while KMT2A rearrangement drives around 70 percent of infant ALL. Menin inhibitors are the first transcription-complex disruptors in routine haematology, and combinations with venetoclax and azacitidine are in phase 3. Differentiation syndrome, QT prolongation and acquired MEN1 mutations that restore binding are the recognised open problems. It is a scaffold certain leukaemias need to keep their genes on, and the first drug against it was approved in 2024.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Menin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Menin"}],"tags":["epigenetic"],"related":[],"cancers":["aml","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["revumenib","ziftomenib"],"companies":[],"institutions":[],"pathways":["menin-kmt2a"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"MEN1","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"one-type","specificityNote":"Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 2 medicines aimed at it (Revumenib, Ziftomenib) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA MEN1: RNA low tissue specificity; no normal tissue stained high; highest cancer staining liver cancer (6 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 8 specific cancer types at or above 0.5 (multiple endocrine neoplasia type 1, parathyroid gland adenoma, multiple endocrine neoplasia, Angiofibroma, lung carcinoid tumor, hereditary neoplastic syndrome and more); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas MEN1 tissue","url":"https://www.proteinatlas.org/ENSG00000133895-MEN1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000133895 associations","url":"https://platform.opentargets.org/target/ENSG00000133895/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7010","ensembl":"ENSG00000133895","uniprot":"O00255","entrez":"4221","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Chandrasekharappa S.C. et al, Science, 1997, \"Positional cloning of the gene for multiple endocrine neoplasia-type 1\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9103196/","biology":"Menin is a scaffold linking KMT2A fusion proteins to chromatin; inhibitors displace the complex and differentiate blasts.","whereFound":["KMT2A-rearranged AML/ALL","NPM1-mutant AML"],"targetClass":"transcription","prevalence":[{"cancerId":"aml","pct":"25-30","measure":"NPM1 mutation","source":"https://www.cbioportal.org/study/summary?id=laml_tcga_pan_can_atlas_2018","note":"KMT2A rearrangement ~5-10%"},{"cancerId":"all-leukemia","pct":"5-10","measure":"KMT2A rearrangement (adult); ~70% infant ALL","source":"https://en.wikipedia.org/wiki/Menin"}]},"route":"/targets/menin/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"id":"grade-3-net","kind":"cancer","name":"Grade 3 well-differentiated neuroendocrine tumour","route":"/cancers/grade-3-net/"},{"id":"all-infant","kind":"cancer","name":"Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)","route":"/cancers/all-infant/"},{"id":"multiple-endocrine-neoplasia","kind":"cancer","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/cancers/multiple-endocrine-neoplasia/"},{"id":"men1-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 1 (MEN1)","route":"/cancers/men1-syndrome/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"aml-npm1-kmt2a","kind":"cancer","name":"NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia","route":"/cancers/aml-npm1-kmt2a/"},{"id":"pancreatic-net","kind":"cancer","name":"Pancreatic neuroendocrine tumours","route":"/cancers/pancreatic-net/"}],"drug":[{"id":"revumenib","kind":"drug","name":"Revumenib","route":"/drugs/revumenib/"},{"id":"ziftomenib","kind":"drug","name":"Ziftomenib","route":"/drugs/ziftomenib/"}],"pathway":[{"id":"cancer-stem-cells-plasticity","kind":"pathway","name":"Cancer stem cells & phenotypic plasticity","route":"/pathways/cancer-stem-cells-plasticity/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"apoptosis-bcl2","kind":"pathway","name":"Intrinsic apoptosis (BCL-2 family)","route":"/pathways/apoptosis-bcl2/"},{"id":"menin-kmt2a","kind":"pathway","name":"Menin / KMT2A (HOXA9-MEIS1 axis)","route":"/pathways/menin-kmt2a/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"term":[{"id":"cancer-stem-cell-theory","kind":"term","name":"Cancer stem cell theory and phenotypic plasticity","route":"/terms/cancer-stem-cell-theory/"},{"id":"differentiation-syndrome","kind":"term","name":"Differentiation syndrome","route":"/terms/differentiation-syndrome/"},{"id":"epigenetic-progenitor-theory","kind":"term","name":"Epigenetic progenitor theory: cancer without a first mutation","route":"/terms/epigenetic-progenitor-theory/"},{"id":"unlocking-phenotypic-plasticity","kind":"term","name":"Hallmark (2022): unlocking phenotypic plasticity","route":"/terms/unlocking-phenotypic-plasticity/"},{"id":"men1-hereditary-net","kind":"term","name":"MEN1 and hereditary neuroendocrine syndromes","route":"/terms/men1-hereditary-net/"}],"target":[{"id":"hoxa9","kind":"target","name":"HOXA9","route":"/targets/hoxa9/"},{"id":"kmt2a","kind":"target","name":"KMT2A (MLL) rearrangement","route":"/targets/kmt2a/"},{"id":"meis1","kind":"target","name":"MEIS1","route":"/targets/meis1/"},{"id":"npm1","kind":"target","name":"NPM1 mutation","route":"/targets/npm1/"}],"trial":[{"id":"augment-101","kind":"trial","name":"AUGMENT-101","route":"/trials/augment-101/"},{"id":"komet-001","kind":"trial","name":"KOMET-001","route":"/trials/komet-001/"}],"pairing":[{"id":"menin-plus-venetoclax-hma","kind":"pairing","name":"Menin inhibitor + venetoclax + azacitidine","route":"/pairings/menin-plus-venetoclax-hma/"}],"idea":[{"id":"idea-fund-precompetitive-undruggable-consortium","kind":"idea","name":"An open-science consortium on the undruggable drivers, open until a candidate","route":"/ideas/idea-fund-precompetitive-undruggable-consortium/"},{"id":"idea-menin-infant-all","kind":"idea","name":"Menin inhibitors for infant KMT2A-rearranged ALL","route":"/ideas/idea-menin-infant-all/"}],"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"},{"id":"menin-inhibitors","kind":"technology","name":"Menin inhibitors","route":"/technologies/menin-inhibitors/"}],"person":[{"id":"eunice-wang","kind":"person","name":"Eunice S. Wang","route":"/people/eunice-wang/"},{"id":"eytan-stein","kind":"person","name":"Eytan M. Stein","route":"/people/eytan-stein/"},{"id":"ghayas-issa","kind":"person","name":"Ghayas C. Issa","route":"/people/ghayas-issa/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-augment-101-revumenib-menin-nature-2023","kind":"paper","name":"AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation","route":"/key-papers/paper-augment-101-revumenib-menin-nature-2023/"}],"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"}]}}