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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
BMPR1B
bone morphogenetic protein receptor type 1B
Chromosome 4 Β· 4q22.3
NCBI Gene: 658Ensembl: ENSG00000138696.12HGNC: HGNC:1077UniProt: A8KAE3
133PubMed Papers
23Diseases
2Drugs
18Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinaseReceptor
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of osteoblast differentiationtransmembrane signaling receptor activityBMP signaling pathwaypositive regulation of bone mineralizationbrachydactyly type A2acromesomelic dysplasia 3brachydactyly type A1tibia fracture
✦AI Summary

BMPR1B (bone morphogenetic protein receptor type 1B) is a serine/threonine kinase receptor that functions as a key regulator of bone and cartilage development through BMP and GDF signaling. Upon ligand binding, BMPR1B forms a heterotetrameric complex with type II receptors, which phosphorylate and activate BMPR1B to initiate SMAD-dependent transcriptional cascades 1. The receptor specifically responds to BMP7/OP-1 and GDF5, positively regulating chondrocyte differentiation and endochondral bone morphogenesis. Beyond skeletal development, BMPR1B has significant reproductive roles: loss-of-function mutations increase ovulation rate and litter size in ewes through altered BMP2/BMP4 and GDF5/GDF9 signaling pathways 12, and BMPR1B variants associate with distinct polycystic ovary syndrome subtypes 3. BMPR1B is implicated in primary ovarian insufficiency etiology 4 and eye development, with pathogenic variants identified in ocular coloboma families 5. Additionally, BMPR1B participates in vascular calcification through eosinophil-derived protein interactions activating Smad1/5/8 signaling 6. Clinically, BMPR1B mutations cause skeletal dysplasias including acromesomelic dysplasia 3 and brachydactyly subtypes. While BMPR1B variants were historically considered for pulmonary arterial hypertension testing, current evidence is disputed with insufficient genetic support 7.

Sources cited
1
BMPR1B forms receptor complexes and interacts with BMP and GDF proteins; functional mutations increase ovulation rate and litter size through BMP2/BMP4 and GDF5/GDF9 signaling
PMID: 32471519
2
BMPR1B mutations (p.Q249R) associate with litter size in sheep; mutation and alternative splicing are mechanisms for increased reproductive success
PMID: 38552245
3
BMPR1B variants associate with reproductive subtype of polycystic ovary syndrome at genome-wide significance
PMID: 32574161
4
BMPR1B is implicated in primary ovarian insufficiency etiology, linked to ovarian development and meiosis pathways
PMID: 34794894
5
Pathogenic BMPR1B variants cause ocular coloboma; knockdown reveals coloboma and microphthalmia phenotypes
PMID: 35034853
6
BMPR1B interacts with eosinophil-derived cationic proteins to activate Smad1/5/8 signaling and promote vascular calcification
PMID: 37279475
7
BMPR1B has disputed evidence for pulmonary arterial hypertension causality and is not recommended for genetic testing due to paucity of genetic evidence
PMID: 37422716
8
BMPR1B functions in hormonal regulation of female reproductive health and folliculogenesis
PMID: 40069456
Disease Associationsβ“˜23
brachydactyly type A2Open Targets
0.77Strong
acromesomelic dysplasia 3Open Targets
0.74Strong
brachydactyly type A1Open Targets
0.67Moderate
tibia fractureOpen Targets
0.50Moderate
diverticular diseaseOpen Targets
0.49Moderate
bone diseaseOpen Targets
0.46Moderate
acromesomelic dysplasia 2BOpen Targets
0.46Moderate
MenorrhagiaOpen Targets
0.45Moderate
coronary artery diseaseOpen Targets
0.43Moderate
brachydactylyOpen Targets
0.42Moderate
hypertensionOpen Targets
0.42Moderate
angina pectorisOpen Targets
0.42Moderate
osteoarthritisOpen Targets
0.39Weak
Abruptio PlacentaeOpen Targets
0.38Weak
Acromesomelic dysplasia, Grebe typeOpen Targets
0.38Weak
colobomaOpen Targets
0.37Weak
metabolic diseaseOpen Targets
0.37Weak
coloboma, ocular, autosomal dominantOpen Targets
0.37Weak
spinal fusionOpen Targets
0.37Weak
spondylolisthesisOpen Targets
0.37Weak
Acromesomelic dysplasia 3UniProt
Brachydactyly A1, DUniProt
Brachydactyly A2UniProt
Pathogenic Variants18
NM_001203.3(BMPR1B):c.585+1G>CLikely pathogenic
Type A2 brachydactyly;Acromesomelic dysplasia 3|Acromesomelic dysplasia 3
β˜…β˜…β˜†β˜†2024
NM_001203.3(BMPR1B):c.1456C>T (p.Arg486Trp)Pathogenic
Type A2 brachydactyly|not provided|Acromesomelic dysplasia 3;Type A2 brachydactyly
β˜…β˜…β˜†β˜†2024β†’ Residue 486
NM_001203.3(BMPR1B):c.247-2A>GPathogenic
Nonpapillary renal cell carcinoma|Acromesomelic dysplasia 3
β˜…β˜†β˜†β˜†2025
NM_001203.3(BMPR1B):c.402_405del (p.Cys135fs)Pathogenic
Type A2 brachydactyly;Acromesomelic dysplasia 3
β˜…β˜†β˜†β˜†2024β†’ Residue 135
NM_001203.3(BMPR1B):c.1111C>T (p.Arg371Ter)Pathogenic
Acromesomelic dysplasia 3;Type A2 brachydactyly
β˜…β˜†β˜†β˜†2024β†’ Residue 371
NM_001203.3(BMPR1B):c.1457G>A (p.Arg486Gln)Likely pathogenic
Type A2 brachydactyly|BMPR1B-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 486
NM_001203.3(BMPR1B):c.599T>A (p.Ile200Lys)Likely pathogenic
Type A2 brachydactyly|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 200
NM_001203.3(BMPR1B):c.988C>T (p.His330Tyr)Likely pathogenic
Acromesomelic dysplasia 3
β˜…β˜†β˜†β˜†2019β†’ Residue 330
NM_001203.3(BMPR1B):c.1448C>T (p.Thr483Ile)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 483
NM_001203.3(BMPR1B):c.952_957del (p.Glu318_Ile319del)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2015β†’ Residue 318
NM_001203.3(BMPR1B):c.447-1G>APathogenic
Brachydactyly type A1D
β˜†β˜†β˜†β˜†2016
NM_001203.3(BMPR1B):c.975A>C (p.Lys325Asn)Pathogenic
Brachydactyly type A1D
β˜†β˜†β˜†β˜†2016β†’ Residue 325
NM_001203.3(BMPR1B):c.91C>T (p.Arg31Cys)Pathogenic
Acromesomelic dysplasia 3
β˜†β˜†β˜†β˜†2015β†’ Residue 31
NM_001203.3(BMPR1B):c.657G>A (p.Trp219Ter)Pathogenic
Acromesomelic dysplasia 3
β˜†β˜†β˜†β˜†2014β†’ Residue 219
NM_001203.3(BMPR1B):c.157T>C (p.Cys53Arg)Pathogenic
Acromesomelic dysplasia 3
β˜†β˜†β˜†β˜†2014β†’ Residue 53
NM_001203.3(BMPR1B):c.361_368del (p.Gly121fs)Pathogenic
Acromesomelic dysplasia 3
β˜†β˜†β˜†β˜†2005β†’ Residue 121
NM_001203.3(BMPR1B):c.1190T>G (p.Met397Arg)Likely pathogenic
Acromesomelic dysplasia 2C, Hunter-Thompson type
β˜†β˜†β˜†β˜†β†’ Residue 397
NM_001203.3(BMPR1B):c.640C>A (p.Arg214Ser)Pathogenic
Acromesomelic dysplasia 2B;Brachydactyly type A1D;Type A2 brachydactyly;Acromesomelic dysplasia 3
β˜†β˜†β˜†β˜†β†’ Residue 214
View on ClinVar β†—
Drug Targets2
DIBOTERMIN ALFAApproved
Activin receptor type-2A agonist
EPTOTERMIN ALFAApproved
Activin receptor type-1 agonist
tibia fracture
Related Genes
SMURF1Protein interaction100%GDF2Protein interaction100%INHBBProtein interaction100%BMP10Protein interaction99%BMP3Protein interaction99%BMP4Protein interaction99%
Tissue Expression6 tissues
Ovary
100%
Brain
89%
Heart
20%
Liver
10%
Lung
8%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
BMPR1BSMURF1GDF2INHBBBMP10BMP3BMP4
PROTEIN STRUCTURE
Preparing viewer…
PDB3MDY Β· 2.05 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.33Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.20 [0.13–0.33]
RankingsWhere BMPR1B stands among ~20K protein-coding genes
  • #3,481of 20,598
    Most Researched133 Β· top quartile
  • #581of 1,025
    FDA-Approved Drug Targets2
  • #2,276of 5,498
    Most Pathogenic Variants18
  • #1,392of 17,882
    Most Constrained (LOEUF)0.33 Β· top 10%
Genes detectedBMPR1B
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
1.00
2
Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.
PMID: 37422716
Genet Med Β· 2023
0.90
3
Eukaryotic expression, Co-IP and MS identify BMPR-1B protein-protein interaction network.
PMID: 32471519
Biol Res Β· 2020
0.80
4
Multiomics Analyses Provide New Insight into Genetic Variation of Reproductive Adaptability in Tibetan Sheep.
PMID: 38552245
Mol Biol Evol Β· 2024
0.70
5
Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis.
PMID: 35034853
Genet Med Β· 2022
0.60