Affinage

BMPR1B

Bone morphogenetic protein receptor type-1B · UniProt O00238

Length
502 aa
Mass
56.9 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMPR1B (ALK-6) is a type I BMP serine/threonine kinase receptor that transduces signals from BMP/GDF ligands to phosphorylate SMAD1/5/8, promote SMAD4 association and nuclear translocation, and activate BMP-responsive transcription, with its internalization and maximal signaling output regulated by TβRIII/beta-arrestin2-mediated endocytosis (PMID:10814522, PMID:19726563). BMPR1B functions partially redundantly with BMPR1A in chondrogenesis, osteogenesis, and ovarian folliculogenesis—double knockouts cause severe chondrodysplasia or granulosa cell tumors—but uniquely prevents chondrocyte hypertrophy, opposes BMPR1A in regulating astrogliosis, and is specifically required for neural crest induction (PMID:15781876, PMID:32764110, PMID:20363875, PMID:20130193, PMID:26780949). Loss-of-function mutations in BMPR1B cause acromesomelic chondrodysplasias of graded severity depending on residual GDF5-binding capacity, primary ovarian insufficiency, and altered pulmonary arterial hypertension signaling, while the sheep FecB (Q249R) gain-of-function mutation increases ovulation rate (PMID:24129431, PMID:26105076, PMID:31769494, PMID:22374147, PMID:11259271). BMPR1B expression is transcriptionally activated by SMAD4 (positive feedback) and ELK1, and post-transcriptionally repressed by miR-125b, miR-144-3p, and miR-1306, linking its regulation to osteogenic differentiation and granulosa cell survival (PMID:31167348, PMID:40666290, PMID:19738052, PMID:28214897, PMID:36212145).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Establishing the core signaling mechanism: constitutively active BMPR1B phosphorylates SMAD8, induces SMAD8–SMAD4 complex formation and nuclear translocation, and activates BMP-responsive promoters, distinguishing it from TGF-β type I receptor signaling.

    Evidence Constitutively active receptor overexpression with Co-IP, reporter assay, and nuclear translocation assay in cultured cells

    PMID:10814522

    Open questions at the time
    • Endogenous ligand specificity for SMAD8 vs SMAD1/5 activation not resolved
    • No structural basis for SMAD8 selectivity
  2. 2001 High

    The Booroola FecB mutation (Q249R in the kinase domain) was identified as a natural variant altering BMPR1B function to increase ovulation rate, establishing BMPR1B as a physiological regulator of ovarian folliculogenesis.

    Evidence Mutation analysis and genetic segregation in two independent sheep flocks with in situ hybridization confirming oocyte/granulosa expression

    PMID:11259271 PMID:11312159

    Open questions at the time
    • Biochemical mechanism by which Q249R alters kinase output not defined
    • Whether FecB acts through altered SMAD or non-SMAD pathways remained unknown
  3. 2005 High

    Conditional double knockout of BMPR1A and BMPR1B revealed that these receptors are functionally redundant for early chondrogenesis, but collectively essential for chondrocyte proliferation, survival, and Sox9/L-Sox5/Sox6 expression in precartilaginous condensations.

    Evidence Cre-lox conditional double knockout mice with histology and gene expression analysis

    PMID:15781876

    Open questions at the time
    • Individual non-redundant functions of BMPR1B in cartilage not yet delineated
    • Downstream transcriptional targets beyond Sox genes not mapped
  4. 2006 High

    Human BMPR1B mutations (R486Q/W) were shown to act as dominant negatives that suppress both SMAD-dependent and SMAD-independent signaling after GDF5 stimulation, directly linking kinase domain mutations to impaired chondrogenesis and skeletal dysplasia.

    Evidence SMAD reporter assays, alkaline phosphatase induction, and chicken micromass chondrogenesis in stably transfected C2C12 cells

    PMID:16957682

    Open questions at the time
    • Identity of SMAD-independent pathways downstream of BMPR1B not fully defined
    • Structural basis for dominant-negative action not resolved
  5. 2009 High

    Two parallel advances refined BMPR1B regulation: TβRIII/beta-arrestin2 was shown to promote ALK6 internalization required for maximal signaling (contrasting surface retention of ALK3), and miR-125b was identified as a direct post-transcriptional repressor binding the BMPR1B 3′ UTR with allele-specific regulation.

    Evidence Co-IP, subcellular localization, and reporter assays for trafficking; luciferase reporter and SNP-specific assays for miR-125b targeting

    PMID:19726563 PMID:19738052

    Open questions at the time
    • Whether TβRIII-mediated internalization operates in all BMPR1B-expressing tissues unknown
    • In vivo significance of the miR-125b SNP (rs1434536) for BMPR1B expression not confirmed
  6. 2010 High

    Conditional knockout studies in multiple tissues revealed BMPR1B's non-redundant functions: it opposes BMPR1A in astrogliosis (BMPR1B-null mice show hyperactive astrocytes via miR-21), and together with BMPR1A it suppresses granulosa cell tumorigenesis, with BMPR1B uniquely required for cumulus expansion and fertility.

    Evidence Conditional single and double knockout mice (GFAP-Cre, granulosa cell-Cre) with histology, pathway analysis, and miR-21 overexpression

    PMID:20130193 PMID:20363875

    Open questions at the time
    • How BMPR1B and BMPR1A achieve opposing regulation of astrocyte hypertrophy at the signaling level not fully resolved
    • Whether tumor suppression requires SMAD-dependent or -independent pathways not determined
  7. 2012 Medium

    BMPR1B missense mutations (S160N, F392L) found in idiopathic pulmonary arterial hypertension patients were shown to alter SMAD8 phosphorylation, with F392L exhibiting gain-of-function signaling, extending BMPR1B disease associations beyond the skeleton and ovary.

    Evidence Immunoblot of pSMAD8 and promoter-reporter transcriptional activation assay

    PMID:22374147

    Open questions at the time
    • Causality between BMPR1B mutations and PAH not established by genetic segregation
    • Effect on pulmonary vascular cells not tested directly
    • Single study without independent replication
  8. 2013 Medium

    A graded loss-of-function model was established: the C53R mutation causes near-complete loss of GDF5 responsiveness and severe Grebe dysplasia, while the R31C mutation causes partial loss and milder du Pan dysplasia, demonstrating that phenotypic severity of skeletal dysplasia correlates with the degree of BMPR1B functional impairment.

    Evidence Luciferase reporter assays and in vitro chondrogenesis assays with mutant receptors; structural analysis

    PMID:24129431 PMID:26105076

    Open questions at the time
    • No crystal structure of mutant BMPR1B–GDF5 complexes
    • Whether partial loss-of-function mutations affect non-SMAD pathways differently not tested
  9. 2016 Medium

    In Xenopus, ALK6 was shown to be uniquely required for neural crest induction after gastrulation through msx2 upregulation at the neural plate border, establishing a non-redundant developmental role distinct from ALK3.

    Evidence Morpholino loss-of-function with in situ hybridization for neural crest markers and epistasis analysis in Xenopus

    PMID:26780949

    Open questions at the time
    • Whether this non-redundant neural crest role is conserved in mammals not confirmed
    • Downstream effectors beyond msx2 not characterized
  10. 2019 High

    SMAD4 was shown to directly bind the BMPR1B promoter, establishing a positive transcriptional feedback loop within canonical BMP/SMAD signaling and linking it to regulation of granulosa cell apoptosis.

    Evidence ChIP and luciferase reporter assay with granulosa cell functional assays

    PMID:31167348

    Open questions at the time
    • Whether SMAD4-mediated feedback operates in tissues beyond ovarian granulosa cells not tested
    • Quantitative impact on receptor levels in vivo not measured
  11. 2020 High

    Multiple 2020 studies resolved distinct BMPR1B functions: GDF5 mutants with preferential BMPR1B binding prevent chondrocyte hypertrophy (distinguishing BMPR1B from BMPR1A in cartilage fate), BMPR1B loss-of-function variants cause primary ovarian insufficiency in humans, SMOC2 variant competitively binds BMPR1B to cause short-limbed dwarfism, and BMPR1B loss causes optic disc coloboma and retinal ganglion cell loss via reduced pSMAD1/5/8.

    Evidence Engineered GDF5-receptor dimerization assays; human POI variant functional assays; SMOC2 knock-in mice with Co-IP; ENU-mutagenesis mouse retinal phenotyping with pSMAD quantification

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

    Open questions at the time
    • Structural basis for BMPR1B-specific anti-hypertrophic signaling not determined
    • Whether SMOC2 competition for BMPR1B occurs in tissues beyond growth plate unknown
    • Retinal phenotype mechanism beyond pSMAD reduction not characterized
  12. 2021 High

    BMPR1B was identified as a marker of quiescent leukemic stem cells in CML; co-activation of SMAD1/5/8 and STAT3 pathways maintains quiescence, and dual inhibition of BMPR1B and JAK2 promotes cell cycle re-entry, extending BMPR1B biology into cancer stem cell maintenance.

    Evidence Single-cell RNA-seq, pharmacological BMPR1B inhibition (E6201), JAK2 inhibition, stromal co-culture quiescence model

    PMID:32001529

    Open questions at the time
    • Whether BMPR1B marks quiescent stem cells in other leukemia types unknown
    • Direct kinase activity of E6201 against BMPR1B not biochemically validated
  13. 2022 Medium

    Additional miRNAs (miR-144-3p, miR-1306) and regulatory axes (METTL3/LINC00657/miR-144-3p and ELK1 transcriptional activation) were identified as BMPR1B regulators in osteogenesis and granulosa cell biology, revealing a multi-layered regulatory network converging on BMPR1B expression.

    Evidence Dual-luciferase reporters, RNA pull-down, siRNA rescue, promoter deletion and mutagenesis, and functional cellular assays

    PMID:35192037 PMID:36212145 PMID:40666290

    Open questions at the time
    • Relative quantitative contribution of each miRNA and transcription factor to BMPR1B levels in vivo not determined
    • Combinatorial regulation by multiple miRNAs not tested simultaneously
    • Each axis validated by single lab only

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis for BMPR1B-specific signaling outputs versus BMPR1A, the full spectrum of SMAD-independent pathways engaged by BMPR1B, and whether the diverse tissue-specific functions (cartilage, ovary, retina, CNS, leukemia) reflect distinct co-receptor or signaling complex configurations.
  • No high-resolution structure of BMPR1B kinase domain bound to SMAD substrates
  • SMAD-independent signaling pathways downstream of BMPR1B remain poorly mapped
  • Tissue-specific co-receptor requirements not systematically characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 5 R-HSA-1474165 Reproduction 4
Partners
ARRB2BMP2BMPR2GDF5SMAD1SMAD4SMAD8TGFBR3
Complex memberships
BMPR1B-BMPR2 heteromeric receptor complexTβRIII-BMPR1B-β-arrestin2 internalization complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The Booroola fecundity (FecB) mutation is a Q249R substitution in the intracellular kinase domain of BMPR1B (ALK-6). BMPR1B mRNA is specifically expressed in oocytes and granulosa cells of the ovary, as shown by in situ hybridization. The mutation segregates fully with the hyperprolific phenotype with no recombinants. Mutation analysis of cDNA/genomic DNA, in situ hybridization, genetic segregation analysis in backcross and half-sib flocks Biology of reproduction High 11259271 11312159
2005 BMPR1A and BMPR1B are functionally redundant during early chondrogenesis in vivo. Single conditional knockouts in cartilage form intact skeletal elements, but double mutants develop severe generalized chondrodysplasia with absent endochondral skeletal elements, increased apoptosis, decreased proliferation, and loss of Sox9, L-Sox5, and Sox6 expression in precartilaginous condensations, demonstrating that BMP signaling through these receptors is required for chondrocyte proliferation, survival, and differentiation. Conditional double knockout mouse genetics (Cre-lox), histology, immunohistochemistry, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 15781876
2000 Constitutively active BMPR1B (ALK-6) phosphorylates Smad8 and induces Smad8 interaction with Smad4, leading to nuclear translocation of Smad8 and transcriptional activation of BMP-responsive promoters (Xvent2). This signaling is distinct from TGF-beta type I receptor (ALK-5), which does not activate Smad8. Constitutively active receptor overexpression, co-immunoprecipitation, reporter gene assay, nuclear translocation assay Biochemical and biophysical research communications High 10814522
2009 TGF-beta type III receptor (TbetaRIII/betaglycan) differentially regulates ALK3 (BMPR1A) and ALK6 (BMPR1B) subcellular trafficking and downstream signaling. TbetaRIII associates with ALK6 through both extracellular and cytoplasmic domains, and together with beta-arrestin2, promotes internalization of ALK6, which is required for maximal BMP-responsive promoter activity. In contrast, TbetaRIII causes cell-surface retention of ALK3. The TbetaRIII-T841A mutant unable to bind beta-arrestin2 cannot internalize ALK6 and cannot maximally stimulate ALK6 signaling. Co-immunoprecipitation, subcellular localization imaging, reporter gene assays (XVent2, 3GC2, ID-1), dominant-negative and mutant receptor studies Molecular biology of the cell High 19726563
2006 The BMPR1B R486Q mutation (dominant-negative) suppresses SMAD-dependent signaling after GDF5 stimulation and almost completely abolishes alkaline phosphatase induction, and inhibits chondrogenesis more strongly than the R486W mutation. R486Q also suppresses SMAD-independent pathways downstream of BMPR1B. These mutations act in a dominant-negative manner within the NOG-GDF5-BMPR1B signaling cascade. Stably transfected C2C12 cells, SMAD activation reporter assay, alkaline phosphatase induction assay, chicken micromass cultures for chondrogenesis European journal of human genetics : EJHG High 16957682
2010 BMPR1A and BMPR1B exert opposing effects on astrocytic hypertrophy after spinal cord injury: conditional ablation of BMPR1A from GFAP-expressing cells causes defective astrocytic hypertrophy, whereas BMPR1B-null mice develop hyperactive reactive astrocytes and smaller lesion volumes. This opposing regulation is mediated, at least in part, through post-transcriptional regulation of astrocytic microRNA-21; overexpression of miR-21 in wild-type astrocytes reduces cell size and GFAP levels. Conditional knockout mice (Cre-lox), double knockout epistasis, in vitro serum-derived astrocyte assays, miR-21 overexpression The Journal of neuroscience High 20130193
2010 Granulosa cell-specific deletion of Bmpr1b causes sterility due to compromised cumulus expansion, while Bmpr1a conditional deletion causes subfertility with reduced ovulation. Double Bmpr1a/Bmpr1b mutant mice develop granulosa cell tumors with evidence of increased TGF-beta and hedgehog signaling, demonstrating that BMPR1A and BMPR1B together suppress ovarian tumorigenesis acting downstream of BMP ligands and upstream of BMP receptor SMADs. Conditional single and double knockout mouse genetics (Cre-lox), tumor histology, signaling pathway analysis Molecular endocrinology (Baltimore, Md.) High 20363875
2009 BMPR1B transcript is a direct target of miR-125b, which binds the 3' UTR of BMPR1B. A SNP (rs1434536) within the miR-125b binding site differentially regulates miR-125b-mediated repression of C and T alleles, providing an allele-specific regulatory mechanism. Luciferase reporter assay, miR-125b mimic overexpression, quantitative RT-PCR Cancer research High 19738052
2013 Homozygous missense (C53R) mutation in BMPR1B causes loss of receptor function: the C53R mutant receptor is partially located at the cell membrane but cannot be activated by its ligand GDF5, as shown by reporter gene assay, and overexpression in an in vitro chondrogenesis assay shows no effect on differentiation. A nonsense mutation (W219*) is predicted to undergo nonsense-mediated mRNA decay, causing loss of function. Reporter gene assay, in vitro chondrogenesis assay, cell membrane localization analysis European journal of human genetics : EJHG Medium 24129431
2015 A hypomorphic BMPR1B mutation (p.Arg31Cys) causes du Pan acromesomelic dysplasia with a significant but lesser loss of BMPR1B function compared to the p.Cys53Arg mutation that causes the more severe Grebe dysplasia, establishing a phenotypic severity gradient based on the degree of functional impairment of the GDF5-BMPR1B ligand-receptor pair. 3D structural analysis, luciferase reporter assay Orphanet journal of rare diseases Medium 26105076
2012 Missense mutations in BMPR1B (S160N and F392L) found in idiopathic pulmonary arterial hypertension patients alter BMP signaling: the F392L mutation promotes SMAD8 phosphorylation and increases transcriptional activation via SMAD8 and SMAD4 above wild-type levels, suggesting a gain-of-function or altered signaling mechanism. Immunoblot analysis of SMAD8 phosphorylation, promoter-reporter transcriptional activation assay Circulation journal Medium 22374147
2017 miR-125b directly binds the 3' UTR of BMPR1B and negatively regulates BMPR1B expression. Knockdown of BMPR1B by siRNA inhibits osteogenic differentiation of human mesenchymal stem cells, and rescuing miR-125b inhibition with si-BMPR1b blocks the enhanced osteogenic capacity, establishing BMPR1B as a functional mediator downstream of miR-125b in osteogenesis. Dual luciferase reporter assay, siRNA knockdown, miR-125b inhibitor/overexpression, ALP/Alizarin Red staining, micro-CT in vivo bone defect model Cellular physiology and biochemistry High 28214897
2019 Smad4 directly binds to a Smad4-binding element (SBE1) in the BMPR1B promoter (region -405 to -200 nt) to enhance transcription of the ovine BMPR1B gene, representing a positive feedback loop in the canonical BMP/Smad signaling pathway. Smad4 also regulates BMPR1B-mediated granulosa cell apoptosis. 5' RACE, luciferase assay, chromatin immunoprecipitation (ChIP), granulosa cell functional assays International journal of molecular sciences High 31167348
2018 miR-125b directly binds the 3' UTR of ovine BMPR1B and reduces BMPR1B mRNA and protein levels in ovine granulosa cells. Silencing BMPR1B enhances granulosa cell apoptosis, while overexpression inhibits it. miR-125b promotes granulosa cell apoptosis by attenuating BMPR1B expression. Luciferase reporter assay, siRNA/overexpression, apoptosis assays in ovine granulosa cells Reproductive sciences Medium 29661099
2020 BMPR1A is necessary for chondrogenic and osteogenic differentiation, while stronger BMPR1B signaling (relative to BMPR1A) prevents chondrocyte hypertrophy and acts as a cartilage stabilizer. GDF5 mutants with reduced BMPR1A affinity but preferential BMPR1B-BMPR2 dimerization show reduced hypertrophic activity, establishing that the balance of BMPR1A vs BMPR1B signaling determines the chondrogenic versus hypertrophic cell fate. GDF5 mutant protein engineering, BMPR1A/BMPR1B-BMPR2 dimerization assay, chondrogenesis/hypertrophy assays in C3H10T1/2 cells and primary chondrocytes, Saos-2 osteogenic assays Journal of cell science High 32764110
2020 BMPR1B variants (p.Phe272Leu) are correctly expressed and properly localized but lead to impairment of downstream BMP signaling, demonstrating that loss-of-function of BMPR1B causes primary ovarian insufficiency (POI) in humans. In vitro functional BMP signaling assays, expression/localization analysis of mutant receptors The Journal of clinical endocrinology and metabolism Medium 31769494
2020 A SMOC2 variant inhibits BMP signaling by competitively binding to BMPR1B, leading to reduced SMAD1/5/9 phosphorylation, defective growth plate chondrogenesis, and short-limbed dwarfism in knock-in mice. Mutant SMOC2 loses its normal binding to COL9A1 and HSPG, and the competitive binding to BMPR1B underlies the skeletal phenotype. SMOC2 knock-in mouse model, Co-immunoprecipitation, in vitro BMP-SMAD1/5/9 signaling assays, histological analysis of growth plates Bone High 33059102
2020 Loss of BMPR1B-mediated signaling (via exon 10 skipping mutation) in the retina leads to reduced pSMAD1/5/8 levels, optic disc coloboma, ventral retinal gliosis (proliferative and hypertrophic), defective optic nerve axons, and loss of retinal ganglion cells, demonstrating that BMPR1B is necessary for optic nerve and ventral retina development. ENU mutagenesis mouse model, fundoscopy, OCT, electroretinography, immunohistology, electron microscopy, pSMAD1/5/8 quantification Investigative ophthalmology & visual science High 32106289
2021 BMPR1B+ leukemic stem cells in chronic myeloid leukemia co-activate Smad1/5/8 and Stat3 pathways, and their quiescence depends on adherence to stromal cells and BMP4 niche signals. Targeting both BMPR1B and Jak2/Stat3 pathways promotes cell cycle re-entry and differentiation of quiescent leukemic stem cells. The BMPR1B inhibitor E6201 also impairs BMP4 production by mesenchymal stromal cells. Single-cell RNA-seq, BMPR1B+ cell sorting and culture, pharmacological inhibition of BMPR1B (E6201) and Jak2, SMAD/Stat3 pathway analysis, stromal co-culture quiescence model Haematologica High 32001529
2020 Co-immunoprecipitation coupled to mass spectrometry identified 23 proteins that specifically interact with BMPR1B (FecB) in ovary extracts, including BMP2, BMP4, GDF5, GDF9, Smad proteins, RhoD, and HSP10, placing BMPR1B in a protein interaction network mediating TGF-beta/BMP signal transduction in the ovary. Eukaryotic expression system, monoclonal antibody preparation, Co-IP/mass spectrometry Biological research Medium 32471519
2010 BMP7 inhibits proliferation of NCI-H460 lung carcinoma cells through BMPR1A and BMPR1B: blocking either receptor with specific antibodies partially reverses BMP7-mediated growth inhibition, and blocking both receptors almost completely offsets the antiproliferative effect, while blocking ACVR1A has no effect. MTT proliferation assay with blocking antibodies against BMPR1A, BMPR1B, and ACVR1A; RT-PCR receptor expression Chinese journal of lung cancer Medium 20673479
2016 In Xenopus laevis, ALK6 (BMPR1B ortholog) is specifically and non-redundantly required for induction of neural crest cell fate after gastrulation. Loss-of-function studies demonstrate that while ALK3 and ALK6 share redundant roles in dorso-ventral patterning, ALK6 uniquely mediates BMP signaling and msx2 upregulation at the neural plate border required for neural crest development. Loss-of-function morpholino knockdown, in situ hybridization for neural crest markers, epistasis analysis in Xenopus BMC developmental biology Medium 26780949
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 acts as a ceRNA to sponge miR-144-3p, thereby upregulating BMPR1B. BMPR1B knockdown abrogates METTL3's pro-osteogenic effect. Dual-luciferase reporter assay, RNA pull-down, qRT-PCR, western blot, alizarin red/ALP staining Cell and tissue research Medium 35192037
2025 Macrophage-derived exosomal BMPR2 forms a functional complex with epithelial BMPR1B (confirmed by molecular docking and confocal co-localization), activating SMAD1-dependent signaling (pSMAD1 and ID1 upregulation) and accelerating AT2-to-AT1 alveolar epithelial cell transdifferentiation to facilitate lung repair in acute lung injury. Proteomic analysis of exosomes, molecular docking, single-cell RNA-seq, confocal colocalization (correlation coefficient 0.94), SMAD1 signaling biochemical assays, near-infrared biodistribution imaging International journal of nanomedicine Medium 40502982
2023 PCTK1 (PCTAIRE kinase 1) negatively regulates BMPR1B expression in colorectal cancer cells; PCTK1 knockout upregulates BMPR1B and increases nuclear translocation of Smad1/5/8, promoting cancer stemness, proliferation, and chemoresistance. BMPR1B knockdown partially reverses these malignant phenotypes in PCTK1-KO cells, placing BMPR1B downstream of PCTK1 in the BMPR1B-Smad1/5/8 signaling pathway. PCTK1 knockout/overexpression cell lines, BMPR1B knockdown rescue, Smad1/5/8 nuclear translocation assay, xenograft tumor growth, RNA-seq/GSEA International journal of molecular sciences Medium 37373155
2025 ELK1 transcription factor enhances BMPR1B transcriptional activity by directly binding to ELK1-binding elements (EBS) in the BMPR1B promoter region (-438 to -208 bp). ELK1 modulates BMPR1B expression and influences granulosa cell apoptosis through the BMPR1B signaling pathway. Luciferase reporter assay, promoter deletion analysis, ELK1 binding site mutagenesis, granulosa cell apoptosis assays Frontiers in cell and developmental biology Medium 40666290
2019 BMPR1B promotes BMP2-mediated luminal progenitor cell maintenance and differentiation in normal breast epithelium. Chronic overexposure to BMP2 (from tumor microenvironment) drives transformation of immature mammary epithelial cells toward a luminal tumor-like phenotype specifically mediated by BMPR1B; BMP4 acts on stem/myoepithelial progenitors through a distinct receptor. Chronic BMP2/BMP4 treatment of human mammary epithelial cells, BMPR1B-specific signaling knockdown/blocking, breast progenitor differentiation assays Stem cell reports Medium 25601208
2022 A 15-bp InDel in the first intron of porcine BMPR1B creates an estrogen response element (ERE) that mediates binding of ESR1 (estrogen receptor alpha) and drives expression of specific BMPR1B transcript variants (T4) in endometrial tissue. Luciferase assays and 5' RACE demonstrated three distinct BMPR1B promoters driving alternative transcripts. Dual-luciferase assay, 5' RACE, ESR1 binding assay, expression analysis in endometrial tissue BMC genomics Medium 36463109
2022 miR-1306 directly inhibits BMPR1B in ovine granulosa cells by binding its 3' UTR. miR-1306 reduces BMPR1B mRNA and protein levels and promotes granulosa cell apoptosis by suppressing BMPR1B expression. Luciferase reporter assay, qPCR, western blot, apoptosis assay in ovine granulosa cells Frontiers in genetics Medium 36212145
2022 BMPR1B promotes proliferation and migration of porcine endometrial stromal cells but inhibits those processes in endometrial epithelial cells, suggesting cell-type-specific roles in endometrial biology. Transcriptome analysis identified pathways including vascular development, gland morphology, cell migration/adhesion, and reproductive system development as regulated by BMPR1B. BMPR1B gain/loss-of-function in immortalized Meishan pig endometrial cells, proliferation and migration assays, transcriptome sequencing, CUT&Tag International journal of biological macromolecules Medium 39732258

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 339 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 329 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 258 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 53 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 40 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
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 quiescent fraction of chronic myeloid leukemic stem cells depends on BMPR1B, Stat3 and BMP4-niche signals to persist in patients in remission. Haematologica 29 32001529
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 25 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
2020 Eukaryotic expression, Co-IP and MS identify BMPR-1B protein-protein interaction network. Biological research 18 32471519
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
2015 Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1. European journal of human genetics : EJHG 17 25758993
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
2017 BMPR1B mutation causes Pierre Robin sequence. Oncotarget 16 28418932
2015 A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia. Orphanet journal of rare diseases 16 26105076
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 15 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
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
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 Sponging of five tumour suppressor miRNAs by lncRNA-KCNQ1OT1 activates BMPR1A/BMPR1B-ACVR2A/ACVR2B signalling and promotes chemoresistance in hepatocellular carcinoma. Cell death discovery 6 38851743
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
2021 An investigation of the effects of BMPR1B, BMP15, and GDF9 genes on litter size in Ramlıç and Dağlıç sheep. Archives animal breeding 6 34159253
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
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 miR-1306 induces cell apoptosis by targeting BMPR1B gene in the ovine granulosa cells. Frontiers in genetics 4 36212145
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 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 Exosomal BMPR2 Macromolecule Facilitates Alveolar Epithelial Cell Repair Through Functional Complex Formation with BMPR1B in Acute Lung Injury. International journal of nanomedicine 1 40502982
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 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