Affinage

ACVR1

Activin receptor type-1 · UniProt Q04771

Length
509 aa
Mass
57.2 kDa
Annotated
2026-06-09
100 papers in source corpus 52 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACVR1/ALK2 is a BMP type I serine/threonine kinase receptor that transduces TGF-β superfamily signals to control mesoderm formation, cardiac and craniofacial development, skeletal chondrogenesis, iron homeostasis, and angiogenesis (PMID:10226013, PMID:11376113, PMID:11376112, PMID:25413979, PMID:28864813, PMID:28232325). Signaling proceeds through a tetrameric receptor complex in which the ALK2 kinase domain heterodimerizes with the type II receptor BMPR2 via their C-terminal lobes, a scaffold required for ligand-induced GS-domain phosphorylation and downstream SMAD1/5/8 activation (PMID:34400635); type II receptors ACVR2A/B and BMPR2 are obligate partners, with BMPR2 also restraining activin/BMP signaling by preventing premature ALK2 oligomerization (PMID:23572558, PMID:29739878). ACVR1 activity is held in check by FKBP12 binding to the GS domain, which stabilizes the inactive kinase, and by ubiquitin turnover: Smurf1-mediated K48 ubiquitination (promoted by AMPK via Smad6 and reversed by the deubiquitinase PSMD14) and BRCC3-reversed K63 ubiquitination at Lys-472/475 tune receptor stability and output (PMID:22977237, PMID:28847510, PMID:31685442, PMID:38557054). Physiologically, ALK2 serves as the type I receptor for Müllerian inhibiting substance signaling through SMAD1 (PMID:11376113, PMID:11376112), drives a BMP6-ALK2-SMAD axis governing hepatocyte hepcidin expression and systemic iron handling (PMID:28864813, PMID:30227271), and is required cell-autonomously in neural crest and endocardial cells for outflow tract, aortic arch, and endocardial cushion development (PMID:15226263, PMID:16140292). The recurrent fibrodysplasia ossificans progressiva (FOP) gain-of-function mutation R206H reduces FKBP12 binding, locks the receptor at the plasma membrane, and confers ligand-independent SMAD1/5/8 activation plus a neofunctional response to Activin A driven by Activin-induced receptor clustering and auto-activation, recapitulating heterotopic endochondral ossification in knock-in mice (PMID:18684712, PMID:19855136, PMID:22508565, PMID:26621707, PMID:34003511). The identical activating residues are mutated in DIPG, where ACVR1 mutants arrest glial differentiation and engage STAT3 and ID transcription factors to promote tumorigenesis (PMID:24705254, PMID:24705250, PMID:30833574, PMID:32142668).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Established that ALK2 is a developmentally essential receptor by showing its loss blocks gastrulation through a requirement in extraembryonic visceral endoderm.

    Evidence Gene targeting and reciprocal chimera analyses in mouse with HNF4 marker readout

    PMID:10226013

    Open questions at the time
    • Did not identify the ligand or downstream SMAD effectors in this context
    • Embryonic versus extraembryonic mechanistic basis of mesoderm support not resolved
  2. 2001 High

    Defined ALK2 as the type I receptor transmitting MIS/AMH signaling via SMAD1, placing it in BMP-like rather than TGF-β/SMAD2 signaling.

    Evidence Reporter assays, dominant-negative ALK2, antisense knockdown, and ex vivo Müllerian duct regression assay

    PMID:11376112 PMID:11376113

    Open questions at the time
    • Type II receptor partner in MIS signaling not defined here
    • Direct ligand-receptor binding not demonstrated
  3. 2005 High

    Showed ALK2 acts cell-autonomously in distinct lineages — neural crest and endocardial endothelium — for cardiac development, linking it to EMT and downstream Msx1/Snail.

    Evidence Wnt1-Cre and Tie2-Cre tissue-specific conditional knockouts with explant assays and pSmad immunostaining

    PMID:15226263 PMID:16140292

    Open questions at the time
    • Specific BMP ligand driving each lineage not identified
    • Relative contribution of SMAD versus non-SMAD output unresolved
  4. 2009 High

    Identified the mechanistic basis of the FOP R206H mutation as reduced FKBP12/FKBP1A binding causing ligand-independent constitutive BMP signaling and aberrant plasma membrane retention.

    Evidence Overexpression in C2C12/HEK293, co-IP for FKBP12 binding, SMAD phosphorylation, subcellular localization, and zebrafish ventralization

    PMID:18684712 PMID:19855136

    Open questions at the time
    • Did not explain how reduced FKBP12 binding mechanistically unlocks the kinase
    • Endogenous-level consequences not yet tested
  5. 2012 High

    Provided structural and in vivo proof: the ALK2-FKBP12 crystal structure showed FOP mutations break inactivating contacts, and an R206H knock-in mouse recapitulated heterotopic endochondral ossification.

    Evidence X-ray crystallography of ALK2 kinase domain with FKBP12/dorsomorphin, and Acvr1R206H/+ knock-in mouse with lineage tracing

    PMID:22508565 PMID:22977237

    Open questions at the time
    • Cellular origin of all ossifying progenitors not fully resolved
    • Inflammatory trigger of lesions not mechanistically defined
  6. 2012 High

    Defined the minimal active receptor complex by showing constitutively active ALK2 still requires type II receptors BMPR2/ACVR2A via a nonenzymatic scaffolding role.

    Evidence Genetic ablation and rescue with kinase-dead and ligand-binding-dead type II receptor constructs, plus in vivo HO model

    PMID:23572558

    Open questions at the time
    • Atomic basis of the scaffolding contribution not defined in this study
    • Stoichiometry of the active complex unresolved here
  7. 2014 Medium

    Showed the FOP-activating residues are recurrently mutated in DIPG and drive constitutive SMAD signaling and ID1/ID2 upregulation in tumor cells, extending ACVR1 from skeletal disease into oncogenesis.

    Evidence Whole-genome sequencing and functional SMAD/target expression assays in tumor cells

    PMID:24705250 PMID:24705254

    Open questions at the time
    • Did not establish how SMAD output drives the differentiation block
    • Cooperating lesions not yet defined at this stage
  8. 2015 High

    Demonstrated the neofunction of FOP-ACVR1: the mutant aberrantly transduces BMP signaling in response to Activin A, which normally only drives TGF-β signaling, explaining ligand-driven heterotopic ossification.

    Evidence FOP patient-derived iPSC mesenchymal stromal cells with Activin A reporter assays and in vivo implantation

    PMID:26621707

    Open questions at the time
    • Did not resolve the conformational mechanism of Activin A neofunction
    • Cell-type specificity of the neofunction not fully mapped
  9. 2017 High

    Connected ACVR1 to systemic iron homeostasis by showing FKBP12 preferentially restrains ALK2 in hepatocytes to limit hepcidin, and that this axis is pharmacologically druggable.

    Evidence Pharmacologic/genetic FKBP12 manipulation, FKBP12-binding mutants, hepcidin assays, and the kinase inhibitor momelotinib in an anemia model

    PMID:28188131 PMID:28864813

    Open questions at the time
    • Physiological ligand integrating inflammatory signals into the hepatic axis not fully resolved
    • Type II receptor usage in hepatocytes addressed only partially
  10. 2019 Medium

    Defined how ACVR1 mutations drive DIPG by arresting oligodendroglial differentiation through STAT3 and transcription-factor upregulation, cooperating with H3K27M and PDGFA, and nominated dual ACVR1/MEK inhibition.

    Evidence In vivo mouse glioma models with genetic epistasis, differentiation and transcription-factor analyses, and inhibitor treatment

    PMID:30833574 PMID:32142668

    Open questions at the time
    • Direct SMAD-dependence of the differentiation arrest not isolated
    • Single-lab in vivo models
  11. 2021 High

    Resolved the activation mechanism: wild-type ALK2 requires upstream ACVR1B/C kinases, whereas R206H bypasses this and is instead activated by Activin A-induced, type-II-receptor-dependent receptor clustering and auto-activation.

    Evidence Optogenetics, live-imaging of receptor clustering, phospho-SMAD assays, kinase-dead constructs, and ACVR2A/B knockdown

    PMID:34003511

    Open questions at the time
    • Quantitative threshold of clustering needed for auto-activation not defined
    • Generalizability across all FOP/DIPG mutants not tested
  12. 2021 High

    Provided the structural framework for signaling, showing the ALK2 and BMPR2 kinase domains heterodimerize via C-terminal lobes to scaffold the active tetrameric complex enabling GS-domain phosphorylation.

    Evidence HDX-MS, SAXS, molecular dynamics, and SMAD signaling assays

    PMID:34400635

    Open questions at the time
    • Full ligand-bound tetramer at high resolution not obtained
    • How disease mutations alter this heterodimer geometry not addressed
  13. 2024 High

    Extended ACVR1 regulation to deubiquitination control, showing BRCC3 removes K63 ubiquitin at Lys-472/475 to activate ALK2-SMAD-BMP signaling in pulmonary artery smooth muscle, with disease relevance to pulmonary hypertension.

    Evidence Ubiquitination site mapping, co-IP, gain/loss-of-function in PASMCs, BRCC3-Tg and Brcc3-/- mouse models, and patient samples

    PMID:38557054

    Open questions at the time
    • Interplay between K63 (BRCC3) and K48 (Smurf1/PSMD14) ubiquitin regulation not integrated
    • Upstream signals controlling BRCC3 activity not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse regulatory inputs — FKBP12 occupancy, K48 and K63 ubiquitin codes, type II receptor scaffolding, and ligand-induced clustering — are quantitatively integrated to set tissue-specific ACVR1 output thresholds remains unresolved.
  • No unified model linking ubiquitin regulation to clustering-based activation
  • Cell-type determinants of Activin A neofunction not fully mapped
  • Structural basis of the active ligand-bound tetramer not yet defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0060089 molecular transducer activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3
Partners
ACVR2AACVR2BBMPR2BRCC3FKBP12PSMD14SMURF1STIP1
Complex memberships
ALK2-BMPR2 type I/type II receptor heterotetramerALK2-FKBP12 inhibitory complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 ActRIA/ALK2 is required for gastrulation; it functions in extraembryonic visceral endoderm to support mesoderm formation, and its absence reduces HNF4 expression. Chimera analyses showed that ActRIA in extraembryonic cells (not embryonic cells) is the critical locus of function during early gastrulation. Gene targeting (knockout), reciprocal chimera analyses, molecular marker analysis (HNF4) Development High 10226013
1999 ALK2 mediates a BMP/Smad signaling pathway on the right side of the Xenopus embryo that antagonizes left-sided Vg1 activity to control cardiac looping. Truncated (dominant-negative) or constitutively active ALK2 on inappropriate sides causes heart reversals; Smad1 and Smad7 are downstream modulators of this pathway. RNA injection into Xenopus embryos (dominant-negative and constitutively active constructs), epistasis with Vg1, Smad1, Smad7 Development High 10556046
2001 ALK2 acts as the type I receptor for Müllerian inhibiting substance (MIS) signaling in the mesenchyme surrounding the Müllerian duct, activating a BMP-like pathway through SMAD1 (not SMAD2) and inducing SMAD6 expression. Dominant-negative ALK2 blocked MIS-induced signaling and Müllerian duct regression; ALK6 was not required. Reporter assays (Tlx2-luc, Gal4DBD-Smad1 fusion), dominant-negative ALK2, antisense knockdown, organ culture regression assay, expression analysis, ALK6 knockout mouse analysis Molecular endocrinology High 11376112 11376113
2003 ALK2 functions as a BMP type I receptor in chondrocytes and, when constitutively activated, induces Indian hedgehog (Ihh) expression in a maturation-independent manner in vitro and in vivo, linking BMP signaling to the Ihh/PTHrP axis during skeletal development. Overexpression of constitutively active ALK2 in chick chondrocytes (in vitro) and chick limb bud (in vivo retroviral infection), gene expression analysis Journal of bone and mineral research Medium 12968668
2004 Neural crest cell-autonomous ALK2 signaling is required for cardiac outflow tract formation and aortic arch development; neural crest-specific deletion impairs migration to the outflow tract, deficient smooth muscle differentiation around aortic arch arteries, and loss of Msx1 expression. Cre/loxP neural crest-specific conditional knockout (Wnt1-Cre), histology, molecular marker analysis Development High 15226263
2005 Endothelial-cell-autonomous ALK2 is required for endocardial cushion formation; endothelial-specific Alk2 deletion impairs endothelial-to-mesenchymal transdifferentiation in the AV canal, reduces Msx1 and Snail expression, and decreases phosphorylation of both BMP and TGF-β Smads. Cre/loxP endothelial-specific conditional knockout (Tie2-Cre), AV canal explant delamination assay, immunostaining for pSmad Developmental biology High 16140292
2007 In silico modeling predicts that the FOP R206H mutation disrupts a salt bridge between R206 and an invariant aspartate in the GS activation domain, creating a pH-sensitive switch that promotes ligand-independent ACVR1 activation; only histidine (not conservative substitutions) creates this effect. Homology modeling of wild-type and mutant ACVR1 based on TβRI crystal structure Clinical orthopaedics and related research Low 17572636
2007 Endoglin activates the ALK2-Smad1 pathway to inhibit prostate cancer cell motility; knockdown of ALK2 (but not ALK5) abolished endoglin-mediated reduction of motility, and constitutively active ALK2 restored low-motility phenotype in endoglin-deficient cells. siRNA knockdown, constitutively active ALK2 overexpression, Smad-specific phosphorylation and promoter activity assays, cell motility assay Oncogene Medium 17496924
2008 ALK2 R206H (FOP mutation) constitutively activates BMP signaling (pSmad1/5 phosphorylation) without ligand binding; R206H shows decreased binding to FKBP12, leading to leaky BMP signal activation and altered subcellular distribution (plasma membrane localization regardless of BMP-2 stimulation). Overexpression in C2C12 and HEK293 cells, co-immunoprecipitation for FKBP12 binding, Smad phosphorylation assays, subcellular fractionation/immunofluorescence Journal of biological chemistry High 18684712
2009 R206H ACVR1 activates BMP signaling in the absence of BMP ligand and mediates BMP-independent chondrogenesis; the mutant exhibits reduced binding to FKBP1A, accounting for increased BMP pathway activity. In zebrafish, R206H causes BMP-independent hyperactivation of BMP signaling and embryonic ventralization. In vitro assays in multiple mammalian cell lines and chick limb bud micromass cultures; COS-7 co-immunoprecipitation for FKBP1A binding; zebrafish embryo injection Journal of Clinical Investigation High 19855136
2009 ALK2 endoglin phosphorylation: ALK2 (and ALK5) phosphorylate endoglin on cytosolic domain threonine residues in prostate cancer cells; constitutively active ALK2 abrogated endoglin's inhibition of cell migration, demonstrating that ALK2-mediated endoglin phosphorylation is a Smad-independent mechanism regulating cell migration. Co-immunoprecipitation, phosphorylation assays with constitutively active ALK2, cell migration assay Carcinogenesis Medium 19736306
2009 ALK2 is required for cardiac looping: dominant-negative ALK2 L343P allele, identified in a patient with atrioventricular septal defects, has impaired kinase activity and dominant-interfering activity in vivo in zebrafish, causing improper AV canal formation. In vitro kinase assay, BMP-specific transcriptional reporter assay, zebrafish embryo RNA injection Circulation Medium 19506109
2010 ALK2 R206H confers constitutive activity to the BMP receptor, leading to increased Smad1 phosphorylation and BMP transcriptional activity; unlike wild-type ALK2, FOP-ALK2 is not inhibited by FKBP12. Mesenchymal cells expressing R206H are hypersensitized to BMP-induced osteoblast differentiation and mineralization in vitro and form increased bone in vivo. Smad1 phosphorylation assay, BMP transcriptional reporter assay, overexpression of inhibitory Smads, FKBP12 binding assay, osteoblast differentiation assay, in vivo implantation of hMSCs in nude mice Journal of bone and mineral research High 19929436
2010 ACVR1 R206H shows weak constitutive BMP pathway activation (pSmad1/5/8), distinct from the strong constitutive Q207D mutant; it shows decreased FKBP1A binding affinity leading to leaky BMP signaling and decreased steady-state R206H protein levels. Wild-type ACVR1 and FKBP1A localize to the plasma membrane upon BMP-2 stimulation, while R206H localizes to the plasma membrane regardless of stimulation. Smad phosphorylation assays, co-immunoprecipitation (FKBP1A binding), immunofluorescence/subcellular localization in C2C12 and HEK293 cells Journal of biological chemistry High 20463014
2011 Loss of ACVR1 in osteoblasts increases bone mass by activating canonical Wnt signaling; osteoblast-specific Acvr1 knockout upregulates Wnt signaling and suppresses Wnt inhibitors SOST and DKK1. BMP7 dose-dependently upregulates SOST and DKK1 in vitro, defining a BMP7-ACVR1-SOST/DKK1 axis that normally inhibits osteogenesis. Inducible Cre-loxP osteoblast-specific knockout, micro-CT bone analysis, Wnt pathway and gene expression analysis, in vitro BMP7 treatment Biochemical and biophysical research communications Medium 21945937
2012 The R206H knock-in mouse (Acvr1R206H/+) recapitulates FOP: first digit malformations and postnatal heterotopic endochondral bone formation. Lesions show inflammatory infiltration followed by robust heterotopic bone formation. Tie2+ lineage progenitor cells contribute to endochondral osteogenesis, and both wild-type and mutant cells contribute to ectopic bone. Gene targeting (knock-in mouse model), radiographic analysis, histology, lineage tracing (Tie2-Cre) Journal of bone and mineral research High 22508565
2012 Crystal structure of ALK2 kinase domain in complex with FKBP12 and dorsomorphin reveals that FOP mutations break critical interactions stabilizing the inactive kinase state, reducing FKBP12 binding and promoting GS-loop and αC-helix rearrangements that enable kinase activation. X-ray crystallography (crystal structure of ALK2 cytoplasmic domain in complex with FKBP12 and dorsomorphin) Journal of biological chemistry High 22977237
2012 Constitutively active ALK2 GS-domain mutants require type II BMP receptors (BmpRII and ActRIIa) for signaling and heterotopic ossification in vivo; the type II receptor contribution is independent of their ligand-binding or kinase function but requires an intact cytoplasmic domain, suggesting a nonenzymatic scaffolding role. Genetic ablation of BmpRII and ActRIIa in cells, rescue by type II receptor expression constructs (kinase-dead, ligand-binding-dead mutants), in vivo HO mouse model Molecular and cellular biology High 23572558
2012 STIP1 (stress-induced phosphoprotein 1) binds ALK2 and activates the SMAD-ID3 signaling pathway to promote ovarian cancer cell proliferation; STIP1 binding to ALK2 (not prion protein) was necessary and sufficient for this proliferative effect. Co-immunoprecipitation, siRNA knockdown, transcriptional reporter assays, cell proliferation assays Cell reports Medium 22884369
2012 Pathogenic FOP ALK2 mutation inhibits iPSC reprogramming and maintenance through constitutive ALK2 activation; specific suppression of ALK2 expression or ALK2 inhibitor treatment rescued iPSC generation, confirming that constitutive ALK2 kinase activity is causally responsible for the reprogramming block. iPSC generation from FOP fibroblasts, ALK2 siRNA knockdown, ALK2 kinase inhibitor treatment Stem cells Medium 22949078
2013 LDN-212854, a selective ALK2-biased BMP type I receptor kinase inhibitor, potently inhibits ALK2 with ~4 orders of magnitude selectivity for BMP over TGF-β/Activin type I receptors and some preference for ALK2 over ALK1 and ALK3; it inhibits heterotopic ossification in a mutant ALK2 transgenic mouse model. In vitro kinase selectivity profiling, cell-based BMP signaling assays, in vivo HO mouse model ACS chemical biology Medium 23547776
2014 ACVR1 mutations in DIPG (same residues mutated in FOP) are constitutively activating, leading to SMAD phosphorylation and increased expression of ID1 and ID2 in tumor cells. Whole-genome sequencing for mutation identification; functional assays showing SMAD phosphorylation and downstream target expression in tumor cells Nature genetics Medium 24705250 24705254
2014 Alk2 R206H mutation accelerates chondrogenic differentiation in mouse embryonic fibroblasts, due in part to enhanced BMP ligand sensitivity; loss of Alk2 severely impairs chondrogenesis despite expression of other BMP type I receptors, demonstrating Alk2 as a direct regulator of early chondrogenic commitment. Acvr1R206H/+ and Acvr1CKO (loss-of-function) mouse embryonic fibroblast chondrogenesis assays, in vivo HEO recruitment assay Stem cells High 24449086
2015 FOP-ACVR1 (R206H) displays neofunction: it abnormally transduces BMP signaling in response to Activin A (which normally only activates TGF-β signaling), enhancing chondrogenesis via aberrant BMP signaling activation in FOP-iPSC-derived mesenchymal stromal cells in vitro and inducing endochondral ossification in vivo. FOP patient-derived iPSC differentiation to mesenchymal stromal cells, BMP/TGF-β pathway reporter assays with Activin A stimulation, in vivo implantation of FOP-iMSCs PNAS High 26621707
2015 ACVR1/ALK2 is required for chondrocyte proliferation and differentiation particularly in craniofacial and axial skeleton; cartilage-specific Acvr1 conditional knockout mice show shortened cranial base, hypoplastic cervical vertebrae, progressive kyphosis, and decreased Smad1/5 and p38 activation. Double knockouts of Acvr1/Bmpr1a or Acvr1/Bmpr1b show perinatal lethal chondrodysplasia, demonstrating coordinated function. Cre/loxP cartilage-specific conditional knockout, skeletal analysis, signaling assays (pSmad, p38), double mutant analysis Journal of bone and mineral research High 25413979
2017 FKBP12 preferentially targets ALK2 in hepatocytes to inhibit hepcidin expression; sequestration of FKBP12 (by rapamycin or tacrolimus) activates hepcidin via BMP-SMAD signaling. ALK2 mutants defective in FKBP12 binding increase hepcidin ligand-independently, and ALK2 free of FKBP12 becomes responsive to the noncanonical inflammatory ligand Activin A. Pharmacologic and genetic FKBP12 manipulation in hepatocytes and mice, ALK2 FKBP12-binding mutants, hepcidin expression assays Blood High 28864813
2017 Momelotinib directly inhibits ACVR1 kinase, reducing hepatocyte hepcidin production via suppression of BMP-SMAD signaling, leading to increased iron mobilization and erythropoiesis; this mechanism (not JAK2-mediated ferroportin regulation) explains momelotinib's anemia benefit. In vitro kinase inhibition assay, rat model of anemia of chronic disease, hepcidin assays, myeloid-specific JAK2 deletion for negative control Blood High 28188131
2017 Crystal structure of ALK2 in complex with LDN-212854 shows type I ATP-competitive inhibitor binding to the kinase hinge region via a single hydrogen bond to His286; specificity arises from the 5-quinoline moiety interacting with water-mediated hydrogen bonds involving Lys235 and Glu248 in the inactive ALK2 conformation. X-ray crystallography Bone High 28918311
2017 FOP ACVR1 mutations in the kinase domain show greater sensitivity to low BMP levels than GS-domain mutations; FOP mutant receptors respond to both BMP and Activin A; constructs lacking the ligand-binding domain retain increased BMP-pSmad1/5/8 pathway activation relative to wild-type, supporting ligand-independent signaling by the mutant receptors. Cell-based signaling assays with various ACVR1 mutant constructs including ligand-binding-domain deletions, dose-response to BMP and Activin A Bone Medium 29097342
2017 AMPK activation (by metformin/aspirin) downregulates ALK2 by enhancing the interaction between Smad6 and Smurf1, leading to Smurf1-mediated K48-linked ubiquitination and proteasomal degradation of ALK2; knockdown of Smad6 or Smurf1 prevented metformin-induced ALK2 reduction. Pharmacological AMPK activation/inhibition, dominant-negative/constitutively-active AMPK, siRNA knockdown of Smad6/Smurf1, co-immunoprecipitation, ubiquitination assay, FOP-iPSC osteogenic differentiation Biochimica et biophysica acta Medium 28847510
2018 ACVR1 R206H mutation (FOP) causes a proinflammatory state through NF-κB and p38MAPK pathway activation in primary monocytes/macrophages; FOP monocytes show prolonged NF-κB activation and abnormal cytokine secretion after LPS stimulation; SMAD phosphorylation was not significantly altered in these immune cells. Primary blood/monocyte/macrophage samples from FOP and control subjects, multiplex cytokine assays, gene expression analysis, NF-κB and p38MAPK pathway assays JCI insight Medium 30429363
2018 BMPR2 inhibits ALK2-mediated activin A and BMP signaling via wild-type ALK2 by preventing ALK2 from oligomerizing with the type II receptors ACVR2A and ACVR2B that are necessary for ALK2 activation; knockdown of BMPR2 potentiates activin A/B-induced SMAD1/5/8 activation through endogenous wild-type ALK2. siRNA knockdown of BMPR2 in multiple myeloma and HepG2 cells, SMAD1/5/8 phosphorylation assays, cell death assays Journal of cell science Medium 29739878
2019 ACVR1 R206H and G328V mutations in DIPG promote tumor initiation by arresting glial/oligodendroglial differentiation and activate STAT3 signaling in vitro; in vivo, ACVR1 R206H with H3.1K27M and p53 deletion in combination with PDGFA signaling significantly decreases survival and increases tumor incidence. In vitro signaling assays, in vivo mouse glioma model (intracranial injection), genetic epistasis, ACVR1 inhibitor treatment Nature communications Medium 30833574
2019 Acvr1 G328V mutation arrests oligodendroglial lineage cell differentiation, driving tumorigenesis in a mouse model of DIPG; mechanistically, mutant Acvr1 upregulates transcription factors controlling differentiation and tumor cell fitness. E6201 was identified as a dual ACVR1/MEK1/2 inhibitor effective against tumor cells in vivo. Mouse models of gliomagenesis, differentiation assays, transcription factor expression analysis, in vivo drug treatment Cancer cell Medium 32142668
2019 PSMD14 deubiquitinase stabilizes ALK2 by removing K48-linked ubiquitin chains (mediated by Smurf1 E3 ligase), thereby positively regulating initiation of the BMP6 signaling pathway; PSMD14 or ALK2 depletion reduces colorectal cancer tumorigenesis and cancer stemness. DUB siRNA library screen, immunoprecipitation, ubiquitination assay, siRNA knockdown, in vivo xenograft model EBioMedicine Medium 31685442
2020 FOP-ACVR1 mutants R206H and G328R signal through multiple modalities in zebrafish: they do not require their ligand-binding domain for ligand-independent BMP signaling; however, intact R206H can respond to both Bmp7 and Activin A. The normal type I BMP receptor BMPR1 is dispensable for FOP-ACVR1-mediated signaling. Zebrafish DV patterning assay, injection of FOP-ACVR1 deletion constructs (ligand-binding domain removed), genetic epistasis with BMPR1 eLife High 32897189
2021 ACVR1R206H is activated by two distinct mechanisms: (1) wild-type ACVR1 is activated by upstream ACVR1B/C kinases; (2) ACVR1R206H activation does not require upstream kinases but is predominantly activated via Activin A-induced receptor clustering that causes auto-activation. Activin A-induced clustering requires type II receptors ACVR2A/B. Optogenetics, live-imaging of receptor clustering, phospho-SMAD1/5 signaling assays, kinase-dead constructs, ACVR2A/B knockdown EMBO journal High 34003511
2021 Structural basis for ALK2/BMPR2 signaling: the kinase domain of type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes; this heterodimer is essential for ligand-induced receptor signaling and serves as the scaffold for the active tetrameric receptor complex that enables GS domain phosphorylation and SMAD activation. Hydrogen-deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS), molecular dynamics simulations, SMAD signaling assays Nature communications High 34400635
2021 FOP-macrophages (ACVR1R206H) show prolonged inflammatory cytokine production and higher Activin A production after M1-like polarization, dampening responses to additional LPS stimulation; macrophages are identified as a source of Activin A that may drive heterotopic ossification. hiPSC-derived macrophages from FOP patients, cytokine multiplex assays, phagocytosis assays, M1/M2 polarization assays Bone Medium 34311122
2022 Anti-ACVR1 bivalent antibodies that block ligand binding paradoxically stimulate heterotopic ossification in FOP by activating FOP-mutant ACVR1 through antibody-mediated receptor dimerization; this property is specific to FOP-mutant ACVR1, while wild-type ACVR1 is inhibited by the same antibodies. Anti-ACVR1 monoclonal antibody generation, in vivo FOP mouse models, signaling assays comparing wild-type and mutant ACVR1 Journal of Clinical Investigation High 35503416 35511419
2022 ACVR1 R206H mutation in sensory neurons causes ACVR1-dependent hyperexcitability and enhanced responses to TRPV1 and TRPA1 agonists in iPSC-derived nociceptive neurons, providing a mechanism for neuropathic pain hypersensitivity observed in FOP patients. Quantitative sensory testing in FOP patients, iPSC-derived sensory neuron differentiation, intracellular and extracellular electrophysiology, TRPV1/TRPA1 agonist response assays, ACVR1 inhibitor treatment Pain Medium 35442931
2024 BRCC3 deubiquitinase activates ALK2 by removing K63-linked ubiquitin from Lys-472 and Lys-475 on ALK2, stabilizing/activating the receptor; this activates SMAD1/5/9 and downstream BMP-PPARγ/p53/Id1 signaling in pulmonary artery smooth muscle cells. BRCC3 downregulation in PAH reduces ALK2-BMP signaling, and overexpression of BRCC3 or de-ubiquitin-mimetic ALK2-K472/475R attenuates PASMC proliferation and experimental pulmonary hypertension in mice. Bioinformatic analysis, co-immunoprecipitation, ubiquitination assay, overexpression/knockdown in PASMCs, SM22α-BRCC3-Tg mouse and Brcc3-/- mouse models, patient samples Circulation High 38557054
2018 ACVR1R206H mutation alters mechanosensing: mutant Acvr1R206H/+ cells inappropriately respond to soft substrates with a spread morphology typical of stiff-substrate responses and pre-osteoblastic differentiation; this is associated with increased RhoA activation and nuclear localization of RUNX2 on soft substrates, demonstrating altered mechanosensing thresholds downstream of increased BMP signaling. Acvr1R206H/+ mouse model, in vitro substrate stiffness assays, RhoA activity assay, RUNX2 nuclear localization imaging, fibroproliferative tissue stiffness measurement Molecular biology of the cell Medium 30379592
2016 ACVR1R206H mutation has cell-type specific effects in human endothelial cells: FOP iPSC-derived endothelial cells show increased SMAD1/5/8 phosphorylation upon BMP4 stimulation but, unlike FOP iPSCs, do not show increased SMAD1/5/8 phosphorylation upon Activin A stimulation; they express more fibrogenic matrix proteins (Collagen 1/2) and can form in low-BMP conditions. Cell-type differences in ACVR1 and type II receptor expression explain context-specific signaling. hiPSC-derived endothelial cell differentiation protocol, SMAD1/5/8 phosphorylation assays with BMP4 and Activin A, gene expression analysis, mineralization assays Stem cell research & therapy Medium 27530160
2016 ACVR1R206H has an altered ligand response: wild-type ACVR1 inhibits BMP2/BMP4 signaling from other BMP type I receptors in a ligand-binding-domain-independent manner, whereas R206H enhances it. BMP6/BMP7 activate wild-type ACVR1 and cause hyper-activation of R206H. Activin A neofunction via R206H requires an intact ligand-binding domain. Reporter assays with wild-type and mutant ACVR1 constructs (including ligand-binding domain deletions), co-expression with BMPR1A/BMPR1B Cellular signalling Medium 27713089
2008 ALK2 G356D mutation (atypical FOP) constitutively activates BMP signaling (pSmad1/5/8, Id1-luc, alkaline phosphatase), but not p38/ERK1/2 or TGF-β/CAGA signaling; its activity is weaker than R206H, which may explain the milder phenotype, and is suppressed by BMP-Smad pathway inhibitors. Overexpression in myoblasts, pSmad1/5/8 assay, Id1-luciferase reporter, alkaline phosphatase assay, pharmacological inhibition Biochemical and biophysical research communications Medium 18952055
2018 FKBP12 suppresses signaling of most ALK2 mutants associated with FOP/DIPG to varying extents; co-expression of BMP type II receptors or ligand stimulation relieves FKBP12 suppression by disrupting the mutant ALK2-FKBP12 interaction. The PF197-8L mutant is uniquely resistant to FKBP12 suppression due to a steric clash between L197 and D36 of FKBP12. Overexpression of 14 ALK2 mutants with/without FKBP12, BMP signaling assays, structural modeling of FKBP12-ALK2 interaction Bone Medium 29551750
2018 ALK3 undergoes ligand-independent homodimerization, while ALK2 does not homodimerize; ALK2 forms heterodimers with ALK3 in a BMP2/BMP6-dependent manner; both ALK3-ALK3 and ALK2-ALK3 receptor complexes functionally induce hepcidin expression in Huh7 cells. Co-immunoprecipitation in Huh7 cells with/without BMP2/BMP6, hepcidin expression assays, Alk2/3 double knockout mice Free radical biology & medicine Medium 30227271
2017 ALK2/ACVR1 and ALK3/BMPR1A, together with BMPR2, mediate pro-angiogenic BMP signaling required for retinal angiogenesis; endothelial-specific deletion of either Alk2/acvr1 or Alk3/Bmpr1a causes delayed radial vascular expansion reminiscent of BMPR2 deletion phenotype. Endothelial-specific inducible Cre/loxP deletion of Alk2, Alk3, and Bmpr2, retinal vascular phenotype analysis Arteriosclerosis thrombosis and vascular biology Medium 28232325

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nature genetics 488 24705254
2014 Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nature genetics 344 24705250
2009 Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Human mutation 335 19085907
2015 Neofunction of ACVR1 in fibrodysplasia ossificans progressiva. Proceedings of the National Academy of Sciences of the United States of America 237 26621707
2017 Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood 209 28188131
2004 The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. Journal of medical genetics 199 15235019
1999 The type I serine/threonine kinase receptor ActRIA (ALK2) is required for gastrulation of the mouse embryo. Development (Cambridge, England) 193 10226013
2009 The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. The Journal of clinical investigation 188 19855136
2008 Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. The Journal of biological chemistry 170 18684712
2012 An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 157 22508565
2012 Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. The Journal of biological chemistry 149 22977237
2004 Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells. Development (Cambridge, England) 144 15226263
2001 Müllerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces SMAD6 expression. Molecular endocrinology (Baltimore, Md.) 144 11376113
2010 ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 138 19929436
2016 Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 135 26896819
2001 The serine/threonine transmembrane receptor ALK2 mediates Müllerian inhibiting substance signaling. Molecular endocrinology (Baltimore, Md.) 135 11376112
2013 Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS chemical biology 134 23547776
2005 Atrioventricular cushion transformation is mediated by ALK2 in the developing mouse heart. Developmental biology 126 16140292
2011 MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2. RNA biology 119 21878751
2020 ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial. Blood advances 111 32915978
2003 ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 105 12968668
2014 Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification. Stem cells (Dayton, Ohio) 91 24449086
2010 Molecular consequences of the ACVR1(R206H) mutation of fibrodysplasia ossificans progressiva. The Journal of biological chemistry 90 20463014
2018 NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI insight 89 30429363
2019 ACVR1 R206H cooperates with H3.1K27M in promoting diffuse intrinsic pontine glioma pathogenesis. Nature communications 86 30833574
2008 Mutational analysis of the ACVR1 gene in Italian patients affected with fibrodysplasia ossificans progressiva: confirmations and advancements. European journal of human genetics : EJHG 84 18830232
2014 Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. Journal of medicinal chemistry 80 25101911
2014 Regulation of ACVR1 and ID2 by cell-secreted exosomes during follicle maturation in the mare. Reproductive biology and endocrinology : RB&E 79 24884710
2015 Regulatory MiR-148a-ACVR1/BMP circuit defines a cancer stem cell-like aggressive subtype of hepatocellular carcinoma. Hepatology (Baltimore, Md.) 78 25271001
2019 ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma. Communications biology 77 31098401
2013 Constitutively active ALK2 receptor mutants require type II receptor cooperation. Molecular and cellular biology 76 23572558
2009 Dominant-negative ALK2 allele associates with congenital heart defects. Circulation 75 19506109
2008 A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H). American journal of medical genetics. Part A 73 18203193
2007 Functional modeling of the ACVR1 (R206H) mutation in FOP. Clinical orthopaedics and related research 72 17572636
2014 ACVR1 mutations in DIPG: lessons learned from FOP. Cancer research 69 25136070
2012 Secreted stress-induced phosphoprotein 1 activates the ALK2-SMAD signaling pathways and promotes cell proliferation of ovarian cancer cells. Cell reports 69 22884369
2020 Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas. Cancer cell 67 32142668
2023 Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood advances 66 37552106
2019 ACVR1 Function in Health and Disease. Cells 66 31683698
2009 The type I BMP receptors, Bmpr1a and Acvr1, activate multiple signaling pathways to regulate lens formation. Developmental biology 65 19733164
1999 Cardiac looping and the vertebrate left-right axis: antagonism of left-sided Vg1 activity by a right-sided ALK2-dependent BMP pathway. Development (Cambridge, England) 63 10556046
2015 The type I BMP receptor ACVR1/ALK2 is required for chondrogenesis during development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 61 25413979
2013 Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorganic & medicinal chemistry letters 61 23639540
2017 The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes. Blood 55 28864813
2007 Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. Oncogene 55 17496924
2012 Pathogenic mutation of ALK2 inhibits induced pluripotent stem cell reprogramming and maintenance: mechanisms of reprogramming and strategy for drug identification. Stem cells (Dayton, Ohio) 54 22949078
2023 Momelotinib (JAK1/JAK2/ACVR1 inhibitor): mechanism of action, clinical trial reports, and therapeutic prospects beyond myelofibrosis. Haematologica 53 36861402
2008 A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor. Biochemical and biophysical research communications 52 18952055
2015 Common mutations in ALK2/ACVR1, a multi-faceted receptor, have roles in distinct pediatric musculoskeletal and neural orphan disorders. Cytokine & growth factor reviews 51 26776312
2012 Deficient signaling via Alk2 (Acvr1) leads to bicuspid aortic valve development. PloS one 51 22536403
2011 Loss-of-function of ACVR1 in osteoblasts increases bone mass and activates canonical Wnt signaling through suppression of Wnt inhibitors SOST and DKK1. Biochemical and biophysical research communications 50 21945937
2016 The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling. Stem cell research & therapy 48 27530160
2019 The deubiquitinating enzyme PSMD14 facilitates tumor growth and chemoresistance through stabilizing the ALK2 receptor in the initiation of BMP6 signaling pathway. EBioMedicine 47 31685442
2018 BMPR2 inhibits activin and BMP signaling via wild-type ALK2. Journal of cell science 46 29739878
2021 Repurposing Vandetanib plus Everolimus for the Treatment of ACVR1-Mutant Diffuse Intrinsic Pontine Glioma. Cancer discovery 41 34551970
2017 miR-208a-3p Suppresses Osteoblast Differentiation and Inhibits Bone Formation by Targeting ACVR1. Molecular therapy. Nucleic acids 41 29858067
2018 ACVR1R206H FOP mutation alters mechanosensing and tissue stiffness during heterotopic ossification. Molecular biology of the cell 39 30379592
2017 Alk2/ACVR1 and Alk3/BMPR1A Provide Essential Function for Bone Morphogenetic Protein-Induced Retinal Angiogenesis. Arteriosclerosis, thrombosis, and vascular biology 38 28232325
2008 Functions of the type 1 BMP receptor Acvr1 (Alk2) in lens development: cell proliferation, terminal differentiation, and survival. Investigative ophthalmology & visual science 38 18566469
2018 MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1. Oncology reports 37 29693185
2014 MicroRNA-130a is up-regulated in mouse liver by iron deficiency and targets the bone morphogenetic protein (BMP) receptor ALK2 to attenuate BMP signaling and hepcidin transcription. The Journal of biological chemistry 37 25002578
2017 Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2. Bone 34 28918311
2012 ACVR1, a therapeutic target of fibrodysplasia ossificans progressiva, is negatively regulated by miR-148a. International journal of molecular sciences 34 22408438
2022 Anti-ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1. The Journal of clinical investigation 33 35511419
2021 Pathogenic ACVR1R206H activation by Activin A-induced receptor clustering and autophosphorylation. The EMBO journal 33 34003511
2017 Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells. Oncogene 33 28459464
2011 The tumor suppressor gene Trp53 protects the mouse lens against posterior subcapsular cataracts and the BMP receptor Acvr1 acts as a tumor suppressor in the lens. Disease models & mechanisms 33 21504908
2019 Cross-talk among AFAP1-AS1, ACVR1 and microRNA-384 regulates the stemness of pancreatic cancer cells and tumorigenicity in nude mice. Journal of experimental & clinical cancer research : CR 32 30819221
2017 Variable signaling activity by FOP ACVR1 mutations. Bone 32 29097342
2016 The Fibrodysplasia Ossificans Progressiva (FOP) mutation p.R206H in ACVR1 confers an altered ligand response. Cellular signalling 32 27713089
2009 Endoglin phosphorylation by ALK2 contributes to the regulation of prostate cancer cell migration. Carcinogenesis 32 19736306
2007 BMP type I receptor ALK2 is essential for proper patterning at late gastrulation during mouse embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 32 17117439
2017 AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation. Biochimica et biophysica acta. Molecular cell research 31 28847510
2011 A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H. Biochemical and biophysical research communications 31 21377447
2021 Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization. Nature communications 30 34400635
2008 Variants in the ACVR1 gene are associated with AMH levels in women with polycystic ovary syndrome. Human reproduction (Oxford, England) 30 18854405
2020 Fibrodysplasia ossificans progressiva mutant ACVR1 signals by multiple modalities in the developing zebrafish. eLife 29 32897189
2017 ALK2/ALK3-BMPR2/ACVR2A Mediate BMP2-Induced Downregulation of Pentraxin 3 Expression in Human Granulosa-Lutein Cells. Endocrinology 29 28977600
2024 BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension. Circulation 28 38557054
2021 ACVR1R206H extends inflammatory responses in human induced pluripotent stem cell-derived macrophages. Bone 28 34311122
2018 Effects of FKBP12 and type II BMP receptors on signal transduction by ALK2 activating mutations associated with genetic disorders. Bone 28 29551750
2011 ALK2 mutation in a patient with Down's syndrome and a congenital heart defect. European journal of human genetics : EJHG 28 21248739
2006 Alk1 and Alk2 are two new cell cycle-regulated haspin-like proteins in budding yeast. Cell cycle (Georgetown, Tex.) 28 16855400
2019 Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva-Derived Endothelial Cells. JBMR plus 27 31768489
2017 Bone morphogenetic protein signaling through ACVR1 and BMPR1A negatively regulates bone mass along with alterations in bone composition. Journal of structural biology 26 29175363
2016 High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva. Disease models & mechanisms 26 27125279
2021 Recent Advances in ALK2 Inhibitors. ACS omega 25 34423181
2017 Shared ACVR1 mutations in FOP and DIPG: Opportunities and challenges in extending biological and clinical implications across rare diseases. Bone 25 28780023
2009 Mutational screening of ACVR1 gene in Brazilian fibrodysplasia ossificans progressiva patients. Clinical genetics 25 19796185
2022 An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice. The Journal of clinical investigation 24 35503416
2023 ACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis. Cancers 23 38201581
2012 ALK2 and BMPR2 knockdown and endothelin-1 production by pulmonary microvascular endothelial cells. Microvascular research 23 23142694
2018 ALK3 undergoes ligand-independent homodimerization and BMP-induced heterodimerization with ALK2. Free radical biology & medicine 21 30227271
2016 Concurrent progress of reprogramming and gene correction to overcome therapeutic limitation of mutant ALK2-iPSC. Experimental & molecular medicine 20 27256111
2009 Functional analysis of saxophone, the Drosophila gene encoding the BMP type I receptor ortholog of human ALK1/ACVRL1 and ACVR1/ALK2. Genetics 20 19620392
2021 MiR-130a Acts as a Tumor Suppressor MicroRNA in Cutaneous Squamous Cell Carcinoma and Regulates the Activity of the BMP/SMAD Pathway by Suppressing ACVR1. The Journal of investigative dermatology 19 33766507
2020 Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma. Journal of medicinal chemistry 19 32369358
2016 BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy. American journal of physiology. Heart and circulatory physiology 19 26873969
2022 ACVR1-activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans. Pain 18 35442931
2020 Prophylactic treatment of rapamycin ameliorates naturally developing and episode -induced heterotopic ossification in mice expressing human mutant ACVR1. Orphanet journal of rare diseases 18 32448372

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