Affinage

BMPR1B

Bone morphogenetic protein receptor type-1B · UniProt O00238

Length
502 aa
Mass
56.9 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 30 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

BMPR1B (ALK6) is a type I BMP receptor serine/threonine kinase that transduces bone morphogenetic protein and GDF5/CDMP-1 signals through canonical receptor-regulated SMADs, governing skeletal patterning, ovarian function, and neural development (PMID:10814522, PMID:16957682, PMID:32764110). Upon activation it phosphorylates Smad1/5/8, driving Smad-Smad4 complex formation, nuclear translocation, and transcription from BMP-responsive promoters with pathway specificity distinct from the TGF-beta receptor ALK5 (PMID:10814522, PMID:32106289, PMID:40119734). Signaling output is shaped by receptor partnerships: preferential BMPR1B-BMPR2 dimerization prevents chondrocyte hypertrophy and stabilizes cartilage (PMID:32764110), the TGF-beta type III receptor recruits beta-arrestin2 to internalize ALK6 and maximize BMP signaling (PMID:19726563), and exosome-delivered BMPR2 can complex with epithelial BMPR1B to activate SMAD1-dependent ID1 expression (PMID:40502982). Genetically, BMPR1B acts redundantly with BMPR1A in chondrogenesis and granulosa-cell tumor suppression but plays non-redundant roles in cumulus expansion, neural crest induction, optic nerve/retinal development, and precerebellar mossy fiber nucleus formation (PMID:15781876, PMID:20130193, PMID:20363875, PMID:26780949, PMID:32106289, PMID:31869353). Loss-of-function and dominant-negative kinase-domain mutations cause acromesomelic chondrodysplasias and brachydactyly with a genotype-phenotype severity gradient correlated to residual signaling, and BMPR1B variants underlie primary ovarian insufficiency (PMID:15805157, PMID:16957682, PMID:24129431, PMID:26105076, PMID:31769494, PMID:40119734). BMPR1B expression is repressed post-transcriptionally by miR-125b, miR-144-3p (via a LINC00657 ceRNA axis), and miR-1306, and is transcriptionally amplified by a Smad4 positive-feedback loop and by ELK1, coupling the receptor to osteogenesis, granulosa-cell survival, and cancer phenotypes (PMID:19738052, PMID:28214897, PMID:31167348, PMID:35192037, PMID:40666290).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2000 High

    Established that constitutively active BMPR1B directly engages the canonical SMAD pathway with ligand-class specificity, defining its core signaling output.

    Evidence Constitutively active receptor overexpression with Co-IP, nuclear translocation, and luciferase reporter assays in C3H10T1/2 and C2C12 cells

    PMID:10814522

    Open questions at the time
    • Did not establish physiological ligand or type II receptor partner
    • Used constitutively active receptor rather than ligand-stimulated endogenous signaling
  2. 2001 High

    Linked a BMPR1B kinase-domain point mutation to ovarian phenotype, first connecting receptor signaling level to ovulation rate and localizing expression to oocytes and granulosa cells.

    Evidence Segregation analysis of the FecB Q249R mutation in sheep flocks plus in situ hybridization

    PMID:11259271 PMID:11312159

    Open questions at the time
    • Mechanistic effect of Q249R on kinase activity not biochemically resolved
    • Did not establish downstream transcriptional targets in granulosa cells
  3. 2005 High

    Defined functional redundancy between BMPR1B and BMPR1A in chondrogenesis and placed BMP receptor signaling upstream of Sox9/L-Sox5/Sox6, while human mutation showed BMPR1B is required for both skeletal and reproductive development.

    Evidence Cartilage-specific conditional double knockout mice with skeletal/IHC analysis; human mutation sequencing and phenotyping

    PMID:15781876 PMID:15805157

    Open questions at the time
    • Single human case without in vitro reconstitution
    • Receptor-specific contributions masked by redundancy
  4. 2006 High

    Demonstrated that disease-causing kinase-domain mutations act as dominant negatives that suppress GDF5-induced SMAD signaling, establishing a mechanistic basis for brachydactyly.

    Evidence Mutagenesis with chicken micromass cultures, stable C2C12 lines, SMAD reporter and ALP induction assays

    PMID:16957682

    Open questions at the time
    • Mechanism of dominant-negative interference (heterodimer poisoning) not directly shown
    • Limited to two engineered mutants
  5. 2009 High

    Revealed receptor-specific trafficking control, showing TbetaRIII/beta-arrestin2-mediated internalization is required for maximal ALK6 signaling, distinguishing it from ALK3.

    Evidence Reciprocal Co-IP, confocal colocalization, beta-arrestin interaction mutant, and BMP-responsive reporters

    PMID:19726563

    Open questions at the time
    • Physiological context of TbetaRIII-ALK6 regulation in vivo not established
    • Endosomal signaling machinery downstream of internalization undefined
  6. 2009 High

    Identified the first post-transcriptional regulator of BMPR1B, with allele-specific miR-125b targeting linking a breast cancer risk SNP to receptor expression.

    Evidence Luciferase 3'UTR reporter with allele-specific constructs, miR-125b mimic overexpression, qRT-PCR

    PMID:19738052

    Open questions at the time
    • Functional consequence on BMP signaling output not measured
    • Did not establish in vivo relevance to tumorigenesis
  7. 2010 High

    Showed BMPR1B and BMPR1A exert opposing post-transcriptional (miR-21) control of reactive astrocyte hypertrophy, and act redundantly as ovarian tumor suppressors while BMPR1B is non-redundantly required for cumulus expansion and fertility.

    Evidence Conditional and global knockout mouse models with injury and tumorigenesis readouts, plus miR-21 overexpression

    PMID:20130193 PMID:20363875

    Open questions at the time
    • Molecular basis of opposing receptor effects on miR-21 unresolved
    • TGF-beta/hedgehog activation in tumors not mechanistically connected to BMPR1B loss
  8. 2010 Medium

    Established that BMP7 anti-proliferative signaling in lung carcinoma operates through both BMPR1A and BMPR1B.

    Evidence MTT proliferation assays with anti-BMPR1A/1B blocking antibodies and RT-PCR in NCI-H460 cells

    PMID:20673479

    Open questions at the time
    • Single lab antibody-blocking approach without genetic confirmation
    • Downstream effectors not identified
  9. 2012 Medium

    Identified a gain-of-function BMPR1B mutation in pulmonary arterial hypertension, demonstrating that hyperactivation of SMAD8 signaling is a distinct disease mechanism.

    Evidence Immunoblot for SMAD8 phosphorylation and promoter-reporter assays

    PMID:22374147

    Open questions at the time
    • Single IPAH cohort and single lab
    • Causality in vascular pathology not established in vivo
  10. 2013 Medium

    Distinguished loss-of-function mechanisms among chondrodysplasia alleles — failed signaling despite membrane localization versus NMD-mediated loss.

    Evidence Immunofluorescence, GDF5-response reporter, and in vitro chondrogenesis assays

    PMID:24129431

    Open questions at the time
    • NMD inference not directly demonstrated at transcript level
    • Single lab
  11. 2015 Medium

    Built a genotype-phenotype severity gradient, correlating degree of residual BMPR1B function with chondrodysplasia severity; concurrently identified BMPR1B as the mediator of BMP2-driven luminal breast cancer initiation.

    Evidence Structural analysis and luciferase reporter assays for hypomorphic mutation; chronic BMP2 transformation assays with BMPR1B-specific intervention in mammary progenitors

    PMID:25601208 PMID:26105076

    Open questions at the time
    • Mechanism converting BMP2/BMPR1B signaling into transformation not defined
    • Single labs for each finding
  12. 2016 Medium

    Defined a non-redundant requirement for ALK6 in neural crest induction, separable from its redundant role in dorso-ventral patterning.

    Evidence Morpholino knockdown in Xenopus laevis with neural crest marker and in situ analysis

    PMID:26780949

    Open questions at the time
    • Mechanistic basis of receptor-specific neural crest requirement unclear
    • Morpholino specificity not orthogonally confirmed
  13. 2017 High

    Demonstrated that BMPR1B is the functional mediator of miR-125b control of osteogenesis through a definitive rescue epistasis experiment.

    Evidence Dual luciferase reporter, siRNA rescue, miR-125b inhibitor/overexpression, ALP/Alizarin Red staining, and in vivo bone defect model in hBMSCs

    PMID:28214897

    Open questions at the time
    • Downstream osteogenic transcriptional program not mapped
    • Other miR-125b targets contributing to phenotype not excluded
  14. 2018 Medium

    Established BMPR1B as a pro-survival factor in granulosa cells, repressed by miR-125b to promote apoptosis.

    Evidence Luciferase 3'UTR reporter, siRNA knockdown, overexpression, and apoptosis assays in ovine granulosa cells

    PMID:29661099

    Open questions at the time
    • Anti-apoptotic effector pathway downstream of BMPR1B undefined
    • Single lab
  15. 2019 High

    Uncovered a Smad4 positive-feedback loop directly amplifying BMPR1B transcription, and defined BMP signaling in precerebellar mossy fiber nucleus formation.

    Evidence 5' RACE, ChIP, luciferase promoter assays and apoptosis assays in granulosa cells; conditional Bmpr1a/Bmpr1b double knockout hindbrain analysis

    PMID:31167348 PMID:31869353

    Open questions at the time
    • In vivo significance of Smad4 feedback not tested
    • Receptor-specific contribution to mossy fiber nuclei obscured by redundancy
  16. 2020 High

    Consolidated BMPR1B's roles via receptor dimerization control of cartilage stabilization, optic nerve/retinal development through pSMAD1/5/8, competitive inhibition by mutant SMOC2, and primary ovarian insufficiency from signaling-impaired variants.

    Evidence GDF5 selectivity mutants and dimerization assays; ENU mutagenesis mouse model with histology/imaging; SMOC2 knock-in mice with binding assays; transfection-based signaling assays for POI variants

    PMID:31769494 PMID:32106289 PMID:32764110 PMID:33059102 PMID:33215411

    Open questions at the time
    • Structural basis of preferential BMPR1B-BMPR2 dimerization not solved
    • How SMOC2 competes with ligand at BMPR1B not fully resolved
  17. 2021 High

    Identified BMPR1B+ leukemic stem cells co-activating Smad1/5/8 and Stat3 with a BMP4 autocrine survival loop, defining a combinatorial therapeutic vulnerability.

    Evidence Single-cell RNA-Seq, leukemic stem cell culture with BMPR1B (E6201) and Jak2 inhibitors, phospho-SMAD/Stat3 immunoblot, quiescence assays

    PMID:32001529

    Open questions at the time
    • Crosstalk mechanism between BMPR1B/SMAD and Jak2/Stat3 not mapped
    • Single lab pharmacological model
  18. 2022 Medium

    Expanded the post-transcriptional regulatory network with miR-1306 repression promoting granulosa apoptosis and a METTL3/LINC00657/miR-144-3p ceRNA axis upregulating BMPR1B to drive osteogenesis.

    Evidence Luciferase reporters, RNA pull-down, siRNA BMPR1B knockdown epistasis, and differentiation/apoptosis assays

    PMID:35192037 PMID:36212145

    Open questions at the time
    • In vivo relevance of ceRNA axis not established
    • Single labs
  19. 2025 Medium

    Added transcriptional activation by ELK1, a brachydactyly-causing kinase variant impairing SMAD4 nuclear accumulation and IHH expression, and a paracrine exosomal BMPR2-BMPR1B complex driving alveolar epithelial transdifferentiation.

    Evidence ChIP and promoter reporters for ELK1; WES and SMAD4 nuclear localization assay for K342E variant; exosome proteomics, docking, colocalization, scRNA-seq and SMAD1 signaling assay for BMPR2-BMPR1B complex

    PMID:40119734 PMID:40502982 PMID:40666290

    Open questions at the time
    • Exosomal BMPR2-BMPR1B complex inferred from colocalization, not biochemical reconstitution
    • ELK1 regulation demonstrated only in ovine granulosa cells

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct ligand and type II receptor partnerships are decoded into divergent biological outcomes (cartilage stabilization vs. hypertrophy, survival vs. apoptosis, tumor suppression vs. cancer initiation) remains unresolved.
  • No structural model linking receptor dimer composition to SMAD output specificity
  • Tissue-specific transcriptional target repertoires largely unmapped
  • Mechanism of context-dependent cooperation versus opposition with BMPR1A unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0060089 molecular transducer activity 3 GO:0016740 transferase activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 6 R-HSA-1266738 Developmental Biology 5 R-HSA-1474165 Reproduction 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
BMPR1ABMPR2GDF5SMAD1SMAD4SMAD8SMOC2TGFBR3
Complex memberships
BMPR1B-BMPR2 type I/type II receptor complexSmad-Smad4 transcriptional complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Constitutively active ALK6 (BMPR1B) phosphorylates Smad8 and induces Smad8 interaction with Smad4, leading to nuclear translocation of Smad8 and cooperative transcriptional activation of the BMP-responsive Xvent2 promoter. Constitutively active TGF-beta type I receptor ALK5 did not activate Smad8, establishing pathway specificity. Constitutively active receptor overexpression, co-immunoprecipitation, nuclear translocation assay, luciferase reporter assay, alkaline phosphatase activity assay in C3H10T1/2 and C2C12 cells Biochemical and biophysical research communications High 10814522
2001 A Q249R missense mutation in the intracellular kinase signaling domain of BMPR1B (FecB mutation) segregates perfectly with the high-ovulation-rate Booroola phenotype in sheep. BMPR1B is expressed specifically in oocytes and granulosa cells of the ovary. Mutation mapping by segregation analysis in backcross/half-sib flocks, in situ hybridization for cell-type localization Biology of reproduction High 11259271 11312159
2005 BMPR1A and BMPR1B are functionally redundant during early chondrogenesis in vivo: mice lacking both receptors in cartilage develop severe generalized chondrodysplasia with loss of Sox9, L-Sox5, and Sox6 expression in precartilaginous condensations, whereas single knockouts form intact cartilaginous elements. Conditional double knockout mice (cartilage-specific Cre), skeletal analysis, immunohistochemistry, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 15781876
2005 A homozygous 8 bp deletion in BMPR1B (del359-366) causes loss of function resulting in acromesomelic chondrodysplasia with genital anomalies (hypoplasia of uterus and ovarian dysfunction), establishing that BMPR1B is required for both skeletal and reproductive organ development. Mutation analysis (sequencing of genomic DNA and cDNA), clinical/radiological phenotyping Journal of medical genetics Medium 15805157
2006 A R486Q mutation in BMPR1B inhibits chondrogenesis more strongly than R486W (both BDA2-causing) and suppresses SMAD-dependent signaling and alkaline phosphatase induction after GDF5 stimulation, establishing that the kinase domain R486 residue is critical for GDF5-BMPR1B signal transduction and that mutations here act as dominant negatives. Chicken micromass cultures (overexpression of mutants), stably transfected C2C12 cells, SMAD-dependent reporter assays, alkaline phosphatase induction assays European journal of human genetics : EJHG High 16957682
2009 The TGF-beta type III receptor (TbetaRIII) differentially regulates ALK6 (BMPR1B) versus ALK3 (BMPR1A) subcellular trafficking: TbetaRIII associates with ALK6 through both extracellular and cytoplasmic domains, recruits beta-arrestin2, and induces ALK6 internalization, which is required for maximal BMP signaling downstream of ALK6. In contrast, TbetaRIII retains ALK3 at the cell surface independently of beta-arrestin2. Co-immunoprecipitation, confocal colocalization, beta-arrestin2 interaction mutant (TbetaRIII-T841A), BMP-responsive promoter reporter assays (XVent2, 3GC2, ID-1, Smad6) Molecular biology of the cell High 19726563
2009 BMPR1B transcript is a direct target of miR-125b, which binds the 3' UTR of BMPR1B and differentially regulates expression depending on the allele at rs1434536 SNP, providing a mechanism linking a breast cancer risk SNP to BMPR1B expression levels. Luciferase reporter assays with 3'UTR constructs, miR-125b mimic overexpression, quantitative RT-PCR Cancer research High 19738052
2010 BMPR1B and BMPR1A exert opposing effects on astrocytic hypertrophy after spinal cord injury: BMPR1A ablation reduces hypertrophic response while BMPR1B ablation produces hyperactive reactive astrocytes and smaller lesion volumes; double knockout reverses both phenotypes. Mechanistically, the two receptors exert opposing effects on post-transcriptional regulation of microRNA-21 in astrocytes, and overexpression of miR-21 reduces astrocytic cell size. Conditional knockout mice (GFAP-Cre), in vivo spinal cord injury model, in vitro serum-derived astrocyte cultures, miR-21 overexpression experiments The Journal of neuroscience : the official journal of the Society for Neuroscience High 20130193
2010 BMPR1B and BMPR1A act redundantly in granulosa cells to suppress ovarian tumor development; BMPR1B single null mice are sterile due to compromised cumulus expansion, and double mutant mice develop granulosa cell tumors with evidence of increased TGF-beta and hedgehog signaling, establishing that BMP receptor signaling is a tumor suppressor pathway in the ovary. Conditional knockout mice (granulosa cell-specific Cre for BMPR1A; BMPR1B global null), fertility assays, histological analysis, signaling pathway analysis Molecular endocrinology (Baltimore, Md.) High 20363875
2012 A BMPR1B F392L missense mutation found in idiopathic pulmonary arterial hypertension patients promotes SMAD8 phosphorylation and increases transcriptional activation via SMAD8 and SMAD8/SMAD4 above wild-type levels, indicating a gain-of-function mechanism for this specific mutation. Immunoblot analysis for SMAD8 phosphorylation, promoter-reporter assays measuring transcriptional activation Circulation journal : official journal of the Japanese Circulation Society Medium 22374147
2013 A C53R missense mutation in BMPR1B (causing acromesomelic chondrodysplasia-Grebe type) partially localizes to the cell membrane but fails to activate downstream signaling upon GDF5 stimulation, demonstrating loss of function; the W219* nonsense mutation leads to premature stop codon subject to nonsense-mediated mRNA decay. Immunofluorescence for membrane localization, reporter gene assay for GDF5 response, in vitro chondrogenesis assay European journal of human genetics : EJHG Medium 24129431
2015 A hypomorphic BMPR1B R31C mutation causes a milder acromesomelic dysplasia (du Pan type) compared to the more severe C53R mutation (Grebe type), with luciferase reporter assays demonstrating significant but less complete loss of BMPR1B function, establishing a genotype-phenotype severity gradient correlated with the degree of functional impairment. 3D structural analysis, luciferase reporter assays Orphanet journal of rare diseases Medium 26105076
2015 BMP2 promotes luminal breast cancer initiation through BMPR1B: chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiates transformation toward a luminal tumor-like phenotype mediated by BMPR1B. Under physiological conditions, BMP2 controls maintenance and differentiation of early luminal progenitors via BMPR1B. Cell transformation assays with BMP2 chronic exposure, BMPR1B-specific intervention, phenotypic characterization of breast stem/progenitor cells Stem cell reports Medium 25601208
2016 ALK6 (BMPR1B) is required non-redundantly for neural crest induction and development in Xenopus laevis post-gastrula; loss-of-function studies show ALK6 is essential for neural crest cell fate induction and subsequent derivative development, while both ALK3 and ALK6 contribute redundantly to dorso-ventral patterning. Loss-of-function (morpholino knockdown) in Xenopus laevis, in situ hybridization for temporal/spatial expression, neural crest marker analysis BMC developmental biology Medium 26780949
2017 miR-125b directly targets the 3'UTR of BMPR1B in human mesenchymal stem cells, suppressing BMPR1B mRNA and protein levels; knockdown of BMPR1B by siRNA inhibits osteogenic differentiation of hBMSCs, and rescuing miR-125b inhibition with si-BMPR1B blocks the enhanced osteogenic capacity, establishing BMPR1B as the functional mediator of miR-125b's effect on osteogenesis. Dual luciferase reporter assay, siRNA knockdown, miR-125b inhibitor/overexpression, qRT-PCR, western blot, ALP/Alizarin Red staining, in vivo bone defect repair model Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology High 28214897
2018 miR-125b directly binds the 3'UTR of ovine BMPR1B, reduces BMPR1B mRNA and protein levels, and promotes apoptosis in ovine granulosa cells via BMPR1B suppression; silencing BMPR1B enhances apoptosis while overexpression inhibits apoptosis, establishing BMPR1B as a pro-survival factor in granulosa cells. Luciferase reporter assay, siRNA knockdown, BMPR1B overexpression, apoptosis assays Reproductive sciences (Thousand Oaks, Calif.) Medium 29661099
2019 Smad4 enhances transcription of the ovine BMPR1B gene by directly binding to Smad-binding elements (SBE1) in the -405 to -200 nt promoter region (PII), establishing a positive feedback mechanism within the BMP/Smad canonical pathway; Smad4 also regulates BMPR1B-mediated granulosa cell apoptosis. 5' RACE (transcription start site mapping), luciferase promoter assays, chromatin immunoprecipitation (ChIP), granulosa cell apoptosis assays International journal of molecular sciences High 31167348
2020 Loss of BMPR1B-mediated signaling (via exon 10-skipping mutation) in mice leads to optic disc coloboma, proliferative/hypertrophic gliosis in the optic nerve head and ventral retina, defective optic nerve axons, and reduced pSMAD1/5/8 levels, demonstrating that BMPR1B is required for retinal and optic nerve development through SMAD1/5/8 signaling. ENU mutagenesis screen, Sanger sequencing (mutation identification), fundoscopy, OCT, ERG, immunohistology (pSMAD1/5/8), electron microscopy Investigative ophthalmology & visual science High 32106289
2020 BMPR1A is required for chondrogenesis and osteogenesis, while preferential BMPR1B-BMPR2 dimerization (induced by GDF5 R399E mutant) prevents chondrocyte hypertrophy, establishing that BMPR1B signaling functions as a cartilage stabilizer that prevents hypertrophic differentiation. GDF5 receptor-selectivity mutants (R399E), BMPR1A/BMPR1B-BMPR2 dimerization assays, chondrogenic and hypertrophic differentiation assays in C3H10T1/2 cells and chondrocytes, Saos-2 osteogenic assays Journal of cell science High 32764110
2020 BMPR1B variants (p.Phe272Leu) causing primary ovarian insufficiency are correctly expressed and localized but lead to impaired downstream BMP signaling, establishing loss of BMPR1B signal transduction as a pathophysiological mechanism for primary ovarian insufficiency in humans. In vitro functional experiments measuring BMP signaling downstream of mutant vs. wild-type receptors (transfection, signaling assays) The Journal of clinical endocrinology and metabolism Medium 31769494
2020 A mutant SMOC2 protein (c.1076 T>G) inhibits BMP signaling by competitively binding to BMPR1B, disrupting normal BMP-SMAD1/5/9 signaling and causing growth plate defects (reduced/disorganized proliferative zones, expanded hypertrophic zones) and short-limbed dwarfism in knock-in mice. Knock-in mouse model, co-immunoprecipitation/binding assays (SMOC2-BMPR1B interaction), in vivo and in vitro BMP-SMAD1/5/9 signaling measurements Bone High 33059102
2021 BMPR1B+ leukemic stem cells co-activate Smad1/5/8 and Stat3 pathways; quiescence of BMPR1B+ leukemic stem cells is induced by tyrosine kinase inhibitor treatment and depends on stromal cell adhesion. Targeting BMPR1B and Jak2/Stat3 together promotes cell cycle re-entry and differentiation of quiescent leukemic stem cells. A BMP4 autocrine loop supports BMPR1B+ cell survival. Single-cell RNA-Seq, CD34+CD38- leukemic stem cell culture model, BMPR1B inhibitor (E6201), Jak2 inhibitor, phospho-SMAD1/5/8 and phospho-Stat3 immunoblot, quiescence/proliferation assays Haematologica High 32001529
2020 CDMP-1 (GDF5/CDMP1) promotes type II collagen and aggrecan synthesis in nucleus pulposus cells through ALK6 (BMPR1B): silencing ALK6 abolishes the pro-synthetic effect of CDMP-1, while ALK6 overexpression amplifies it, establishing ALK6 as the functional receptor mediating CDMP-1 effects on extracellular matrix in nucleus pulposus cells. siRNA knockdown of ALK6, overexpression of ALK6, measurement of collagen II, aggrecan, MMP9, MMP13, TIMP4 expression by qPCR/western blot in human primary NP cells European review for medical and pharmacological sciences Medium 33215411
2022 miR-1306 directly targets the 3'UTR of ovine BMPR1B, reducing BMPR1B mRNA and protein expression in ovine granulosa cells and promoting apoptosis through suppression of BMPR1B. Luciferase reporter assay (3'UTR), qPCR, western blot, apoptosis assays Frontiers in genetics Medium 36212145
2022 METTL3-mediated m6A methylation of LINC00657 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via the LINC00657/miR-144-3p/BMPR1B axis; LINC00657 functions as a ceRNA to upregulate BMPR1B by sponging miR-144-3p, and BMPR1B knockdown abrogates the effect of METTL3 on osteogenesis. Dual-luciferase reporter assay, RNA pull-down assay, siRNA knockdown of BMPR1B, ALP/Alizarin Red staining, western blot Cell and tissue research Medium 35192037
2025 Macrophage-derived exosomal BMPR2 forms a functional complex with epithelial BMPR1B, activating SMAD1-dependent signaling (confirmed by BMPR1B-SMAD1 colocalization and enhanced ID1 expression) and accelerating type II to type I alveolar epithelial cell transdifferentiation to facilitate tissue repair in acute lung injury. Proteomic analysis of exosomes, molecular docking, co-localization confocal microscopy, scRNA-seq, biochemical SMAD1 phosphorylation assay, near-infrared biodistribution tracking, multiplex immunofluorescence International journal of nanomedicine Medium 40502982
2025 A novel heterozygous BMPR1B c.1024A>G (p.K342E) variant in the kinase domain reduces nuclear SMAD4 accumulation in BMP4-stimulated 293T transfectants, indicating impaired kinase activity and downstream SMAD1/5/8 phosphorylation, with consequent suppression of IHH expression and disrupted BMP-mediated skeletal patterning, causing brachydactyly type A4/D overlap. Whole-exome sequencing, Sanger sequencing, structural analysis, SMAD4 nuclear localization assay in transfected 293T cells American journal of medical genetics. Part A Medium 40119734
2025 ELK1 transcription factor enhances BMPR1B transcriptional activity by directly binding to ELK1-binding elements (EBS) in the -438 to -208 bp region of the BMPR1B promoter in ovine granulosa cells, and modulates BMPR1B expression and granulosa cell apoptosis through the BMPR1B signaling pathway. Luciferase reporter assays (promoter deletion constructs), ChIP for ELK1 binding, ELK1 overexpression/knockdown, apoptosis assays in ovine granulosa cells Frontiers in cell and developmental biology Medium 40666290
2010 BMP7 inhibits proliferation of lung large carcinoma NCI-H460 cells through BMPR1A and BMPR1B: blocking either BMPR1A or BMPR1B individually partially reverses BMP7-mediated inhibition, and blocking both together almost completely abolishes the effect, establishing that BMP7 signals anti-proliferative effects via both type I receptors. MTT proliferation assay with anti-BMPR1A and/or anti-BMPR1B blocking antibodies, RT-PCR for receptor expression Zhongguo fei ai za zhi = Chinese journal of lung cancer Medium 20673479
2019 BMP signaling through BMPR1B is involved in precerebellar mossy fiber nuclei formation derived from the rhombic lip; double knockout of Bmpr1a and Bmpr1b demonstrates that BMP signaling is required for mossy fiber nucleus formation but is not required for inferior olivary nucleus development. Conditional double knockout mice (Bmpr1a/Bmpr1b), histological analysis of hindbrain nuclei PloS one Medium 31869353

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Proceedings of the National Academy of Sciences of the United States of America 341 15781876
2001 Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biology of reproduction 330 11259271
2001 The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene. The Journal of endocrinology 259 11312159
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
2010 BMPR1a and BMPR1b signaling exert opposing effects on gliosis after spinal cord injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 129 20130193
2009 A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer research 112 19738052
2010 Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development. Molecular endocrinology (Baltimore, Md.) 96 20363875
2009 Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig. Reproduction (Cambridge, England) 79 19359354
2005 A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies. Journal of medical genetics 73 15805157
2012 Missense mutations of the BMPR1B (ALK6) gene in childhood idiopathic pulmonary arterial hypertension. Circulation journal : official journal of the Japanese Circulation Society 72 22374147
2017 MiR-125b Regulates the Osteogenic Differentiation of Human Mesenchymal Stem Cells by Targeting BMPR1b. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 62 28214897
2009 Polymorphism of BMPR1B, BMP15 and GDF9 fecundity genes in prolific Garole sheep. Tropical animal health and production 54 20020203
2006 A novel R486Q mutation in BMPR1B resulting in either a brachydactyly type C/symphalangism-like phenotype or brachydactyly type A2. European journal of human genetics : EJHG 51 16957682
2007 Patterns of expression of messenger RNAs encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 during follicular development and characterization of ovarian follicular populations in ewes carrying the Woodlands FecX2W mutation. Biology of reproduction 50 17715428
2000 Mouse smad8 phosphorylation downstream of BMP receptors ALK-2, ALK-3, and ALK-6 induces its association with Smad4 and transcriptional activity. Biochemical and biophysical research communications 50 10814522
2015 Disequilibrium of BMP2 levels in the breast stem cell niche launches epithelial transformation by overamplifying BMPR1B cell response. Stem cell reports 49 25601208
2022 METTL3-mediated LINC00657 promotes osteogenic differentiation of mesenchymal stem cells via miR-144-3p/BMPR1B axis. Cell and tissue research 42 35192037
2009 The transforming growth factor-beta type III receptor mediates distinct subcellular trafficking and downstream signaling of activin-like kinase (ALK)3 and ALK6 receptors. Molecular biology of the cell 36 19726563
2016 Genotyping of Novel SNPs in BMPR1B, BMP15, and GDF9 Genes for Association with Prolificacy in Seven Indian Goat Breeds. Animal biotechnology 34 27135147
2018 Expression Analysis of the Prolific Candidate Genes, BMPR1B, BMP15, and GDF9 in Small Tail Han Ewes with Three Fecundity (FecB Gene) Genotypes. Animals : an open access journal from MDPI 33 30274220
2020 BMPR1A is necessary for chondrogenesis and osteogenesis, whereas BMPR1B prevents hypertrophic differentiation. Journal of cell science 32 32764110
2021 The quiescent fraction of chronic myeloid leukemic stem cells depends on BMPR1B, Stat3 and BMP4-niche signals to persist in patients in remission. Haematologica 31 32001529
2020 BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency. The Journal of clinical endocrinology and metabolism 31 31769494
2012 Booroola BMPR1B mutation alters early follicular development and oocyte ultrastructure in sheep. Reproduction, fertility, and development 30 22281082
2021 The expression and mutation of BMPR1B and its association with litter size in small-tail Han sheep (Ovis aries). Archives animal breeding 29 34109270
2018 Generation of gene-edited sheep with a defined Booroola fecundity gene (FecBB) mutation in bone morphogenetic protein receptor type 1B (BMPR1B) via clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9. Reproduction, fertility, and development 28 31039970
2013 Association of BMPR-1B and GDF9 genes polymorphisms and secondary protein structure changes with reproduction traits in Mehraban ewes. Gene 28 23583795
2013 Differential ovarian morphometry and follicular expression of BMP15, GDF9 and BMPR1B influence the prolificacy in goat. Reproduction in domestic animals = Zuchthygiene 26 23581245
2019 Smad4 Feedback Enhances BMPR1B Transcription in Ovine Granulosa Cells. International journal of molecular sciences 24 31167348
2018 miR-125b Contributes to Ovarian Granulosa Cell Apoptosis Through Targeting BMPR1B, a Major Gene for Sheep Prolificacy. Reproductive sciences (Thousand Oaks, Calif.) 24 29661099
2016 Differential requirement of bone morphogenetic protein receptors Ia (ALK3) and Ib (ALK6) in early embryonic patterning and neural crest development. BMC developmental biology 24 26780949
2013 BMPR1B up-regulation via a miRNA binding site variation defines endometriosis susceptibility and CA125 levels. PloS one 24 24339876
2018 Polymorphism of GDF9 and BMPR1B genes and their association with litter size in Markhoz goats. Reproduction in domestic animals = Zuchthygiene 21 29696699
2017 Downregulation of microRNA-1274a induces cell apoptosis through regulation of BMPR1B in clear cell renal cell carcinoma. Oncology reports 20 29192325
2020 A SMOC2 variant inhibits BMP signaling by competitively binding to BMPR1B and causes growth plate defects. Bone 19 33059102
2016 BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian disease development. Reproduction (Cambridge, England) 19 27486268
2013 Homozygous missense and nonsense mutations in BMPR1B cause acromesomelic chondrodysplasia-type Grebe. European journal of human genetics : EJHG 19 24129431
2022 Long noncoding RNA BMPR1B-AS1 facilitates endometrial cancer cell proliferation and metastasis by sponging miR-7-2-3p to modulate the DCLK1/Akt/NF-κB pathway. Cell cycle (Georgetown, Tex.) 18 35404759
2000 Correlation between ALK-6 (BMPR-IB) distribution and responsiveness to osteogenic protein-1 (BMP-7) in embryonic mouse bone rudiments. Growth factors (Chur, Switzerland) 18 10705576
2018 Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with complex digit malformation and male infertility. European journal of human genetics : EJHG 17 29581481
2017 BMPR1B mutation causes Pierre Robin sequence. Oncotarget 17 28418932
2015 Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1. European journal of human genetics : EJHG 17 25758993
2015 A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia. Orphanet journal of rare diseases 17 26105076
2011 Variation in BMPR1B, TGFRB1 and BMPR2 and control of dizygotic twinning. Twin research and human genetics : the official journal of the International Society for Twin Studies 17 21962132
2021 LncRNA SNHG6/miR-125b-5p/BMPR1B Axis: A New Therapeutic Target for Triple-Negative Breast Cancer. Frontiers in oncology 16 34026654
2020 BMPR-1B, BMP-15 and GDF-9 genes structure and their relationship with litter size in six sheep breeds reared in Egypt. BMC research notes 16 32299511
2021 Survey of the relationship between polymorphisms within the BMPR1B gene and sheep reproductive traits. Animal biotechnology 14 34586970
2020 Mutation in Bmpr1b Leads to Optic Disc Coloboma and Ventral Retinal Gliosis in Mice. Investigative ophthalmology & visual science 13 32106289
2021 Association between novel variants in BMPR1B gene and litter size in Mongolia and Ujimqin sheep breeds. Reproduction in domestic animals = Zuchthygiene 12 34543455
2020 CDMP1 promotes type II collagen and aggrecan synthesis of nucleus pulposus cell via the mediation of ALK6. European review for medical and pharmacological sciences 12 33215411
2018 A novel homozygous variant in BMPR1B underlies acromesomelic dysplasia Hunter-Thompson type. Annals of human genetics 12 29322508
2022 Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis. Genetics in medicine : official journal of the American College of Medical Genetics 11 35034853
2019 Down-regulated hsa_circ_0067934 facilitated the progression of gastric cancer by sponging hsa-mir-4705 to downgrade the expression of BMPR1B. Translational cancer research 11 35117027
2020 Study on the correlation between BMPR1B protein in sheep blood and reproductive performance. Journal of animal science 10 32300800
2012 Common genetic variants of the BMP4, BMPR1A, BMPR1B, and ACVR1 genes, left ventricular mass, and other parameters of the heart in newborns. Genetic testing and molecular biomarkers 10 22971142
2024 A repertoire of single nucleotide polymorphisms (SNPs) of major fecundity BMPR1B gene among 75 sheep breeds worldwide. Theriogenology 9 38401385
2014 Polymorphism and nucleotide sequencing of BMPR1B gene in prolific Assam hill goat. Molecular biology reports 9 24535267
2023 Polymorphisms Analysis of BMP15, GDF9 and BMPR1B in Tibetan Cashmere Goat (Capra hircus). Genes 8 37239462
2022 FecB mutation and litter size are associated with a 90-base pair deletion in BMPR1B in East Friesian and Hu crossbred sheep. Animal biotechnology 8 34985398
2022 Integrated Proteotranscriptomics of the Hypothalamus Reveals Altered Regulation Associated with the FecB Mutation in the BMPR1B Gene That Affects Prolificacy in Small Tail Han Sheep. Biology 8 36671764
2024 Sponging of five tumour suppressor miRNAs by lncRNA-KCNQ1OT1 activates BMPR1A/BMPR1B-ACVR2A/ACVR2B signalling and promotes chemoresistance in hepatocellular carcinoma. Cell death discovery 7 38851743
2023 Progress on the effect of FecB mutation on BMPR1B activity and BMP/SMAD pathway in sheep. Yi chuan = Hereditas 7 37077164
2022 A unique 15-bp InDel in the first intron of BMPR1B regulates its expression in Taihu pigs. BMC genomics 7 36463109
2021 An investigation of the effects of BMPR1B, BMP15, and GDF9 genes on litter size in Ramlıç and Dağlıç sheep. Archives animal breeding 7 34159253
2020 Investigating the Polymorphism of Bone Morphogenetic Protein Receptor-1B (BMPR1B) Gene in Markhoz Goat Breed. Animals : an open access journal from MDPI 7 32899883
2024 Polymorphisms of the BMPR1B, BMP15 and GDF9 fecundity genes in four Chinese sheep breeds. Archives animal breeding 6 40655877
2023 CRISPR/Cas mediated disruption of BMPR-1B gene and introduction of FecB mutation into the Caprine embryos using Easi-CRISPR strategy. Theriogenology 6 37619525
2021 Association of a genetic polymorphism in the BMPR-1B gene, and non-genetic factors with the natural prolificacy of the Colombian-haired sheep. Tropical animal health and production 6 33712982
2019 Molecular cloning of ESR1, BMPR1B, and FOXL2 and differential expressions depend on maternal age and size during breeding season in cultured Asian yellow pond turtle (Mauremys mutica). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 6 30922947
2017 Prolonged use of alendronate alters the biology of cranial repair in estrogen-deficient rats' associated simultaneous immunohistochemical expression of TGF-β1+, α-ER+, and BMPR1B. Clinical oral investigations 6 29197953
2024 Functional effects of BMPR1B in porcine endometrium provides novel insights into the high fecundity of Taihu pigs. International journal of biological macromolecules 5 39732258
2023 Detection of carrier Booroola (FecB) allele in BMPR1B gene of MEGA (Merino × Garut) sheep and its association with growth traits. Journal, genetic engineering & biotechnology 5 36790660
2022 BMPR1B Polymorphisms (rs1434536 and rs1970801) are Associated With Breast Cancer Susceptibility in Northwest Chinese Han Females: A Case-Control Study. Clinical breast cancer 5 35501253
2022 miR-1306 induces cell apoptosis by targeting BMPR1B gene in the ovine granulosa cells. Frontiers in genetics 5 36212145
2010 [BMP7 signaling via BMPR1A, BMPR1B inhibits the proliferation of lung large carcinoma NCI-H460 cell]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 5 20673479
2024 The Impact of Novel BMPR1B Mutations on Litter Size in Short-Tailed Gobi Sheep and Larger-Tailed Ujimqin Sheep. Veterinary sciences 4 39057981
2023 A novel variant in BMPR1B causes acromesomelic dysplasia Grebe type in a consanguineous Moroccan family: Expanding the phenotypic and mutational spectrum of acromesomelic dysplasias. Bone 4 37524292
2022 Two Retrotransposon Elements in Intron of Porcine BMPR1B Is Associated with Phenotypic Variation. Life (Basel, Switzerland) 4 36295085
2021 BMPR1B gene in brachydactyly type 2-A family with de novo R486W mutation and a disease phenotype. Molecular genetics & genomic medicine 4 33486847
2015 Novel mutation in the BMPR1B gene (R486L) in a Polish family and further delineation of the phenotypic features of BMPR1B-related brachydactyly. Birth defects research. Part A, Clinical and molecular teratology 4 25776145
2011 Polymorphism analysis of BMPR1B gene by forced RFLP and PCR-SSCP techniques and expression of the mutation in introgressed sheep. Tropical animal health and production 4 22086410
2024 Association of polymorphism in the promotor area of the caprine BMPR1B gene with litter size and body measurement traits in Damani goats. Tropical animal health and production 3 38649642
2020 Genetic Variability in the microRNA Binding Sites of BMPR1B, TGFBR1, IQGAP1, KRAS, SETD8 and RYR3 and Risk of Breast Cancer in Colombian Women. OncoTargets and therapy 3 33311986
2019 Common Genetic Variants on Bone Morphogenetic Protein Receptor Type IB (BMPR1B) Gene Are Predictive for Carotid Intima-Media Thickness. Circulation journal : official journal of the Japanese Circulation Society 3 30713213
2025 Exosomal BMPR2 Macromolecule Facilitates Alveolar Epithelial Cell Repair Through Functional Complex Formation with BMPR1B in Acute Lung Injury. International journal of nanomedicine 2 40502982
2025 ELK1 regulates BMPR1B transcriptional activity in ovine granulosa cells. Frontiers in cell and developmental biology 2 40666290
2024 Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 38703029
2023 Integrated High-Throughput Bioinformatics (Microarray, RNA-Seq, and RNA Interaction) and qRT-PCR Investigation of BMPR1B Axis as a Potential Diagnostic Biomarker of Isfahan Breast Cancer. Advanced biomedical research 2 37434942
2019 Analyses with double knockouts of the Bmpr1a and Bmpr1b genes demonstrate that BMP signaling is involved in the formation of precerebellar mossy fiber nuclei derived from the rhombic lip. PloS one 2 31869353
2013 Negative mutation screening of the NOG, BMPR1B, GDF5, and FGF9 genes indicates further genetic heterogeneity of the facioaudiosymphalangism syndrome. Clinical dysmorphology 2 22968293
2025 Association of hypertension and genetic variants in MYH9 and BMPR1B with increased proteinuria in sickle cell disease. Clinical biochemistry 1 41265744
2024 Congenital hallux valgus occurs in Fibrodysplasia Ossificans Progressiva and BMPR1B-associated dysplasia: an important distinction. BMC medical genomics 1 38879467
2023 PCTAIRE Protein Kinase 1 (PCTK1) Suppresses Proliferation, Stemness, and Chemoresistance in Colorectal Cancer through the BMPR1B-Smad1/5/8 Signaling Pathway. International journal of molecular sciences 1 37373155
2023 Screening for causative mutations in ovine BMPR1B and BMP15 genes and their homologous fragments in human. Journal of assisted reproduction and genetics 1 37455267
2017 [Polymorphism analysis of MTHFR，BMPR1B and TYMS in microtia]. Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery 1 29871275
2016 [Bushen Tiaojing Recipe Regulated Expressions of BMPR I[/ALK6-Smads in Mouse Oocytes Cul- ture in vitro]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine 1 30641014
2025 A Novel Heterozygous c.1024A>G Variant in BMPR1B Causes Either Isolated Brachydactyly Type A4 With Variable Expressivity or Incomplete Type A4 Overlapping Type D in a Chinese Han Pedigree. American journal of medical genetics. Part A 0 40119734
2025 Novel BMPR1B::AFF2 in a Sinonasal Region Non-Keratinizing Squamous Cell Carcinoma. Head and neck pathology 0 40944786
2025 Polymorphism of the BMPR1B Variants for Prolific Traits in the Indonesian Local Ettawah Goat. Animals : an open access journal from MDPI 0 41096377
2025 Long noncoding RNA BMPR1B-DT promotes anoikis and reduces proliferation in ovarian cancer. BMC cancer 0 41413870

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