{"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","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 (Momelotinib, Pacritinib) 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 ACVR1: RNA low tissue specificity; high antibody staining in 2 normal tissues. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms); Open Targets associates it with 2 specific cancer types at or above 0.5 (myelofibrosis, primary myelofibrosis); 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 ACVR1 tissue","url":"https://www.proteinatlas.org/ENSG00000115170-ACVR1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000115170 associations","url":"https://platform.opentargets.org/target/ENSG00000115170/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:171","ensembl":"ENSG00000115170","uniprot":"Q04771","entrez":"90","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Matsuzaki et al, J. Biol. Chem, 1993, \"A widely expressed transmembrane serine/threonine kinase that does not bind activin, inhibin, transforming growth factor beta, or bone morphogenic factor\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8389764/","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/"}]}}