{"entity":{"id":"mpl","kind":"target","name":"MPL (thrombopoietin receptor)","aka":["TPO receptor","TPOR","THPOR","CD110","MPL proto-oncogene, thrombopoietin receptor"],"tldr":"MPL is the receptor that tells the bone marrow to make platelets. Romiplostim and eltrombopag switch it on to raise platelet counts; in some myeloproliferative neoplasms a mutant partner protein, calreticulin, grips it and keeps it on.","summary":"MPL (chromosome 1p34.2) is the thrombopoietin receptor that regulates haematopoietic stem cell renewal, megakaryocyte differentiation and platelet formation; thrombopoietin binding triggers rapid JAK2 phosphorylation and docking of STAT5, SHIP, GRB2, SOS1 and PI3K, and the cascades that follow drive megakaryocyte proliferation, survival and differentiation (UniProt P40238). In OnCo it is the receptor that the TPO agonists romiplostim (a peptide fused to an antibody Fc fragment) and eltrombopag (a small molecule binding the transmembrane region) activate; the receptor that frameshift-mutant calreticulin binds and activates in CALR-mutant essential thrombocythaemia and primary myelofibrosis, which the antibody INCA033989 blocks; and one of the three drivers (JAK2, CALR, MPL) that ruxolitinib acts regardless of.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:7217","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7217"},{"label":"UniProt P40238","url":"https://www.uniprot.org/uniprotkb/P40238/entry"},{"label":"NCBI Gene 4352","url":"https://www.ncbi.nlm.nih.gov/gene/4352"}],"tags":["wave5-target"],"related":["inca033989","ruxolitinib","jak2"],"cancers":["myeloproliferative-neoplasms","essential-thrombocythaemia","aml","mds"],"sections":[],"technologies":["transfusion-support"],"targets":[],"drugs":["romiplostim","eltrombopag"],"companies":[],"institutions":[],"pathways":["jak-stat"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"MPL","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"Tumour-associated overexpression: 1 antibody (Romiplostim) aim at the antigen, which HPA finds with no normal tissue stained high; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA MPL: RNA low tissue specificity; blood lineage lineage enriched (granulocytes 1 nTPM); no normal tissue stained high. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Leukaemia); Open Targets associates it with 2 specific cancer types at or above 0.5 (primary myelofibrosis, essential thrombocythemia). (Rule 5 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas MPL tissue","url":"https://www.proteinatlas.org/ENSG00000117400-MPL/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas MPL pathology","url":"https://www.proteinatlas.org/ENSG00000117400-MPL/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000117400 associations","url":"https://platform.opentargets.org/target/ENSG00000117400/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7217","ensembl":"ENSG00000117400","uniprot":"P40238","entrez":"4352","firstDescribed":1992,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Vigon et al, Proc. Natl. Acad. Sci. U.S.A, 1992, \"Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1608974/","biology":"MPL has no kinase of its own and signals through JAK2, so JAK inhibitors act below it whatever the driver. The INCA033989 record explains that CALR frameshift mutations give the protein a positively charged tail that lets it bind and activate MPL on the cell surface, switching on JAK-STAT signalling without thrombopoietin.","whereFound":["Megakaryocytes and haematopoietic stem cells","Essential thrombocythaemia and primary myelofibrosis (MPL as driver; CALR-mutant activation)","Thrombocytopenia in AML and MDS (TPO agonist use in the corpus records)"],"targetClass":"surface-antigen","prevalence":[]},"route":"/targets/mpl/","neighbours":{"drug":[{"id":"eltrombopag","kind":"drug","name":"Eltrombopag","route":"/drugs/eltrombopag/"},{"id":"inca033989","kind":"drug","name":"INCA033989","route":"/drugs/inca033989/"},{"id":"romiplostim","kind":"drug","name":"Romiplostim","route":"/drugs/romiplostim/"},{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"}],"target":[{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"},{"id":"stat5","kind":"target","name":"STAT5 (STAT5A, STAT5B)","route":"/targets/stat5/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"essential-thrombocythaemia","kind":"cancer","name":"Essential thrombocythaemia (ET)","route":"/cancers/essential-thrombocythaemia/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"},{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"}],"technology":[{"id":"transfusion-support","kind":"technology","name":"Transfusion support and anaemia management","route":"/technologies/transfusion-support/"}],"pathway":[{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"}]}}