BMPR2

Chr 2AD

bone morphogenetic protein receptor type 2

Also known as: BMPR-II, BMPR3, BMR2, BRK-3, POVD1, PPH1, T-ALK

The protein is a transmembrane serine/threonine kinase receptor that binds bone morphogenetic proteins and activins to regulate SMAD transcriptional pathways involved in bone formation, embryogenesis, and adipogenesis. Mutations cause primary pulmonary hypertension (both familial and sporadic forms) and pulmonary veno-occlusive disease with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, reflecting its essential role in vascular development.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismADLOEUF 0.193 OMIM phenotypes
Clinical SummaryBMPR2
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 5.88
OE 0.08 (0.040.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.06Z-score
OE missense 0.76 (0.700.82)
429 obs / 567.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.040.19)
00.351.4
Missense OE0.76 (0.700.82)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 4 / 47.9Missense obs/exp: 429 / 567.2Syn Z: 1.92
DN
0.3495th %ile
GOF
0.5955th %ile
LOF
0.76top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.19
GOF1 literature citation
DN1 literature citation

Literature Evidence

DNIn addition, transfection of cysteine-substituted BMPR2 markedly reduced basal and BMP4-stimulated transcriptional activity of a BMP/SMAD-responsive luciferase reporter gene (3GC2wt-Lux), compared with wildtype BMPR2, suggesting a dominant-negative effect of these mutants on SMAD signaling.PMID:12045205
GOFHowever, all mutants studied demonstrate a gain of function involving upregulation of p38(MAPK)-dependent proproliferative pathways.PMID:12045205
LOFNonsense mutations in BMPR2 are amongst the most common mutations found, where the insertion of a premature termination codon causes mRNA degradation via activation of the nonsense-mediated decay pathway leading to a state of haploinsufficiency.PMID:32733669

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BMPR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Idiopathic Pulmonary Arterial HypertensionHeritable Pulmonary Arterial HypertensionUnaffected Mutation Carriers: Healthy Participants With a Known BMPR2 Gene Mutation and Normal Pulmonary Pressure and RV Function on Echo

Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals

RECRUITING
NCT05584722Vanderbilt University Medical CenterStarted 2022-11-01
Solid TumorsHematologic CancersMetastatic Cancers

Phase 2 Study Assessing Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations

ACTIVE NOT RECRUITING
NCT02304809Phase PHASE2UNICANCERStarted 2014-10-13
Vemurafenib
Pulmonary Hypertension Due to Left Heart DiseasePulmonary Hypertension (PH)Heart Failure

Evaluation of the BMPR2-Activin Signaling Pathway in Group II Pulmonary Hypertension.

RECRUITING
NCT07537517Hospital General Universitario Gregorio MarañonStarted 2025-11-01
Breast CancerER-positive Breast CancerHER2-negative Breast Cancer

Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer

ACTIVE NOT RECRUITING
NCT05826964Phase PHASE2University of MiamiStarted 2023-06-12
AI+CDK4/6iSERD+CDK4/6imTOR inhibitor + AI
Heart Defects, CongenitalPulmonary Arterial HypertensionGenetic Testing

Genes Associated With Development of Pulmonary Arterial Hypertension in Patients With Congenital Shunt Lesions

RECRUITING
NCT02691689Phase NAUniversitaire Ziekenhuizen KU LeuvenStarted 2015-11
Genetic testing
Idiopathic Pulmonary Arterial HypertensionHeritable Pulmonary Arterial HypertensionPulmonary Arterial Hypertension Associated With Connective Tissue Disease

Right Ventricle Lipid in Pulmonary Arterial Hypertension (PAH)

RECRUITING
NCT05462574Vanderbilt University Medical CenterStarted 2023-01-17
No Intervention
Breast CancerMetastatic Breast CancerTriple Negative Breast Cancer

Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies

RECRUITING
NCT07340541Phase PHASE2UNC Lineberger Comprehensive Cancer CenterStarted 2026-02-16
SERD* + abemaciclibSERD* + everolimusSERD* + everolimus or capecitabine
Clinical Literature
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