{"entity":{"id":"npm1","kind":"target","name":"NPM1 mutation","aka":[],"tldr":"NPM1 is the most common mutation in adult leukaemia. It moves a nuclear protein into the cytoplasm and, it turns out, makes the leukaemia dependent on menin.","summary":"NPM1 exon 12 frameshift mutations occur in ~30% of adult AML (50-60% of normal-karyotype AML). Favourable risk without FLT3-ITD (ELN 2022), but relapses are common and MRD by NPM1 transcript PCR is the best-validated molecular MRD marker in AML. NPM1-mutant blasts rely on the menin-KMT2A complex; revumenib (October 2025) and ziftomenib (November 2025) are approved for relapsed/refractory NPM1-mutated AML.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Nucleophosmin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nucleophosmin"}],"tags":["driver","mrd-marker"],"related":["menin","flt3","npm1-mutation"],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["revumenib","ziftomenib"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd-negative-cr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"NPM1","role":[],"sources":[],"specificity":"tumour-specific","distribution":"one-type","specificityNote":"Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (NPM1 mutation) absent from normal cells. HPA NPM1: RNA low tissue specificity; high antibody staining in 45 normal tissues; highest cancer staining breast cancer (12 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 3 specific cancer types at or above 0.5 (non-small cell lung carcinoma, acute myeloid leukemia, dyskeratosis congenita); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"NPM1 mutation label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b650f696-3391-4274-8b55-a5f5e9d04769","note":"Susceptible NPM1 mutation, relapsed or refractory"},{"label":"Human Protein Atlas NPM1 tissue","url":"https://www.proteinatlas.org/ENSG00000181163-NPM1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000181163 associations","url":"https://platform.opentargets.org/target/ENSG00000181163/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7910","ensembl":"ENSG00000181163","uniprot":"P06748","entrez":"4869","firstDescribed":1986,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Chan P.-K. et al, J. Biol. Chem, 1986, \"Amino acid sequence of protein B23 phosphorylation site\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3944116/","biology":"Nucleophosmin is a nucleolar chaperone; the mutant acquires a nuclear export signal, delocalising to the cytoplasm and dysregulating HOX gene expression via menin-dependent chromatin binding.","whereFound":["Adult AML (~30%)","Normal-karyotype AML (50-60%)"],"targetClass":"other","prevalence":[{"cancerId":"aml","pct":30,"measure":"mutation","note":"~50-60% of cytogenetically normal AML"}]},"route":"/targets/npm1/","neighbours":{"target":[{"id":"flt3","kind":"target","name":"FLT3","route":"/targets/flt3/"},{"id":"hoxa9","kind":"target","name":"HOXA9","route":"/targets/hoxa9/"},{"id":"meis1","kind":"target","name":"MEIS1","route":"/targets/meis1/"},{"id":"menin","kind":"target","name":"Menin","route":"/targets/menin/"}],"biomarker":[{"id":"npm1-mutation","kind":"biomarker","name":"NPM1 mutation","route":"/biomarkers/npm1-mutation/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-npm1-kmt2a","kind":"cancer","name":"NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia","route":"/cancers/aml-npm1-kmt2a/"}],"drug":[{"id":"revumenib","kind":"drug","name":"Revumenib","route":"/drugs/revumenib/"},{"id":"ziftomenib","kind":"drug","name":"Ziftomenib","route":"/drugs/ziftomenib/"}],"term":[{"id":"eln-risk","kind":"term","name":"ELN 2022 risk classification","route":"/terms/eln-risk/"},{"id":"mrd-negative-cr","kind":"term","name":"MRD-negative complete remission","route":"/terms/mrd-negative-cr/"}],"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/"}],"person":[{"id":"timothy-ley","kind":"person","name":"Timothy J. Ley","route":"/people/timothy-ley/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"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/"}]}}