BMPR2

Chr 2AD

bone morphogenetic protein receptor type 2

ENSG00000204217UniProt: Q13873

On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044)

Primary Disease Associations & Inheritance

Pulmonary hypertension, familial primary, 1, with or without HHTMIM #178600
AD
Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associatedMIM #178600
AD
Pulmonary venoocclusive disease 1MIM #265450
AD
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
7
Active trials
Clinical Summary— BMPR2
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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
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 5.88
OE 0.08 (0.04–0.19)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.06Z-score
OE missense 0.76 (0.70–0.82)
429 obs / 567.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.70–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 4 / 47.9Missense obs/exp: 429 / 567.2Syn Z: 1.92

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Pulmonary hypertension, familial primary, 1, with or without HHT

MIM #178600

Molecular basis of disorder known

Autosomal dominant

Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated

MIM #178600

Molecular basis of disorder known

Autosomal dominant

Pulmonary venoocclusive disease 1

MIM #265450

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dysregulated Smooth Muscle Cell BMPR2-ARRB2 Axis Causes Pulmonary Hypertension.
Wang L et al.·Circ Res
2023
BMPR2 Mutation and Metabolic Reprogramming in Pulmonary Arterial Hypertension.
Cuthbertson I et al.·Circ Res
2023Review
Cathepsin L Promotes Pulmonary Hypertension via BMPR2/GSDME-Mediated Pyroptosis.
Peng Z et al.·Hypertension
2024
Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension.
Bisserier M et al.·Circulation
2021Functional
Anti-remodeling therapies in pulmonary arterial hypertension.
Boucherat O et al.·Trends Pharmacol Sci
2025Review
Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.
Gräf S et al.·Nat Commun
2018
Emerging role of BMPs/BMPR2 signaling pathway in treatment for pulmonary fibrosis.
Ye Q et al.·Biomed Pharmacother
2024Review
Vascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling.
Yanagihara T et al.·Am J Respir Crit Care Med
2023
Single-cell RNA sequencing reveals that BMPR2 mutation regulates right ventricular function via ID genes.
Du M et al.·Eur Respir J
2022
Impact of BMPR2 mutation on the severity of pulmonary arterial hypertension: a systematic review and meta-analysis.
Wu J et al.·Respir Res
2025Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
BMPR2 Splice-Site Variant in a Patient With Pulmonary Arteriovenous Malformation and Delayed-Onset Pulmonary Arterial Hypertension: A Case Report and Mechanistic Phenocopy Hypothesis.
Mathavan A et al.·Am J Med Genet A
2026Case report
TRPC6 governs brown adipose thermogenesis via a BMPR2-p38 MAPK signaling axis.
Xie D et al.·Mol Metab
2026
POSTN+ fibroblast‑secreted small extracellular vesicles drive macrophage M2 polarization through BMP4/BMPR2/Smad signaling.
Zhang C et al.·Oncol Rep
2026🔓 Open Access
Breast Cancer Reveals Latent BMPR2-Related Susceptibility to Pulmonary Hypertension.
Toro V et al.·Circulation
2026🔓 Open Access
Predictive value of TRIB3 combined with BMPR2 for major adverse cardiovascular events in elderly coronary heart disease patients undergoing percutaneous coronary intervention.
Zhang Q et al.·J Med Biochem
2026🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
Breast CancerMetastatic Breast CancerTriple Negative Breast Cancer

Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies

NOT YET RECRUITING
NCT07340541Phase PHASE2UNC Lineberger Comprehensive Cancer CenterStarted 2026-02
SERD* + abemaciclibSERD* + everolimusSERD* + everolimus or capecitabine
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 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
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
Leukemia, Monocytic, AcutePediatric AML

Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children

RECRUITING
NCT05313958Phase PHASE2, PHASE3Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityStarted 2021-12-01
CladribineG-CSFCytarabine

External Resources

Links to major genomics databases and tools