{"entity":{"id":"acvr1","kind":"target","name":"ACVR1 (ALK2)","aka":["ALK2"],"tldr":"ACVR1 (ALK2) is the receptor that raises hepcidin, the hormone that hides iron from the bone marrow. Momelotinib and pacritinib block it as well as JAK2, which is why they improve, rather than worsen, the low red-cell counts of myelofibrosis.","summary":"ACVR1 (chromosome 2q24.1) encodes ALK2, a bone morphogenetic protein type I receptor that forms heterotetrameric complexes with the type II receptors AMHR2, ACVR2A or ACVR2B; on binding of ligands such as BMP7 or BMP9 the type II receptors transphosphorylate it, and its kinase domain then phosphorylates SMAD1, SMAD5 and SMAD8; it acts across bone, heart, cartilage, nervous and reproductive development and also suppresses TGF-beta/activin signalling by competing for the type II receptor (UniProt Q04771). In OnCo, ACVR1 is the receptor that drives hepcidin production and that momelotinib and pacritinib inhibit in addition to JAK2, lowering hepcidin, freeing iron for red-cell production and improving the anaemia of myelofibrosis.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:171","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:171"},{"label":"UniProt Q04771","url":"https://www.uniprot.org/uniprotkb/Q04771/entry"},{"label":"NCBI Gene 90","url":"https://www.ncbi.nlm.nih.gov/gene/90"}],"tags":["wave5-target"],"related":["jak2"],"cancers":["myeloproliferative-neoplasms","primary-myelofibrosis"],"sections":[],"technologies":["kinase-inhibitors"],"targets":[],"drugs":["momelotinib","pacritinib"],"companies":[],"institutions":[],"pathways":["tgf-beta","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":"ACVR1","hgnc":"HGNC:171","ensembl":"ENSG00000115170","uniprot":"Q04771","entrez":"90","biology":"In myelofibrosis the target is ACVR1 in the hepcidin pathway rather than in the malignant clone: the pacritinib record notes that sparing JAK1 while blocking JAK2, FLT3, IRAK1 and ACVR1 lets it be used with very low platelet counts, and the momelotinib record credits ACVR1 inhibition for its effect on anaemia.","whereFound":["Hepcidin regulation (anaemia of myelofibrosis)","Bone morphogenetic protein signalling in normal development"],"targetClass":"kinase","prevalence":[]},"route":"/targets/acvr1/","neighbours":{"target":[{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"}],"cancer":[{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"primary-myelofibrosis","kind":"cancer","name":"Primary myelofibrosis","route":"/cancers/primary-myelofibrosis/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"momelotinib","kind":"drug","name":"Momelotinib","route":"/drugs/momelotinib/"},{"id":"pacritinib","kind":"drug","name":"Pacritinib","route":"/drugs/pacritinib/"}],"pathway":[{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"}]}}