Menu
GeneBe

BMPR2

bone morphogenetic protein receptor type 2, the group of Type 2 receptor serine/threonine kinases

Basic information

Region (hg38): 2:202376326-202567751

Previous symbols: [ "PPH1" ]

Links

ENSG00000204217NCBI:659OMIM:600799HGNC:1078Uniprot:Q13873AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • pulmonary hypertension, primary, 1 (Strong), mode of inheritance: AD
  • pulmonary hypertension, primary, 1 (Definitive), mode of inheritance: AD
  • heritable pulmonary arterial hypertension (Supportive), mode of inheritance: AD
  • congenital heart disease (Limited), mode of inheritance: AD
  • pulmonary arterial hypertension (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pulmonary hypertension, primary 1; Pulmonary venoocclusive disease 1ADCardiovascular; Pharmacogenomic; PulmonaryWhile prognosis is overall poor, medical therapy (eg, with calcium antagonists, anticoagulants, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial; Exposure to agents such as fenfluramine has been described as greatly increasing the risk of diseaseCardiovascular; Pulmonary601742; 1863023; 10903931; 11115457; 10973254; 11015450; 12358323; 12446270; 16429403; 16429395; 15965979; 18356561; 20956135; 19749199; 19713419; 19555857; 21801371

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BMPR2 gene.

  • Primary pulmonary hypertension (297 variants)
  • Pulmonary hypertension, primary, 1 (274 variants)
  • not provided (119 variants)
  • Inborn genetic diseases (46 variants)
  • Pulmonary hypertension, primary, 1;Pulmonary venoocclusive disease 1, autosomal dominant (37 variants)
  • Pulmonary arterial hypertension;Idiopathic and/or familial pulmonary arterial hypertension (24 variants)
  • Pulmonary arterial hypertension (24 variants)
  • Idiopathic and/or familial pulmonary arterial hypertension;Pulmonary arterial hypertension (18 variants)
  • not specified (12 variants)
  • Pulmonary arterial hypertension associated with congenital heart disease (8 variants)
  • BMPR2-related condition (7 variants)
  • Pulmonary venoocclusive disease 1, autosomal dominant (6 variants)
  • Genetic non-acquired premature ovarian failure (4 variants)
  • Pulmonary venoocclusive disease 1, autosomal dominant;Pulmonary hypertension, primary, 1 (3 variants)
  • Pulmonary arterial hypertension associated with another disease;Pulmonary arterial hypertension;Pulmonary arterial hypertension associated with connective tissue disease (2 variants)
  • Pulmonary hypertension, primary, dexfenfluramine-associated (2 variants)
  • Tooth agenesis, selective, 1 (2 variants)
  • Developmental disorder (1 variants)
  • BMPR2-related disorders (1 variants)
  • 8 conditions (1 variants)
  • 9 conditions (1 variants)
  • Drug- or toxin-induced pulmonary arterial hypertension;Pulmonary arterial hypertension associated with another disease;Pulmonary arterial hypertension (1 variants)
  • Pulmonary arterial hypertension associated with congenital heart disease;Pulmonary arterial hypertension associated with another disease;Pulmonary arterial hypertension (1 variants)
  • Pulmonary arterial hypertension;Pulmonary arterial hypertension associated with another disease;Pulmonary arterial hypertension associated with HIV infection (1 variants)
  • Pulmonary arterial hypertension associated with another disease (1 variants)
  • Progressive myositis ossificans (1 variants)
  • Pulmonary arterial hypertension associated with another disease;Pulmonary arterial hypertension (1 variants)
  • Pulmonary hypertension, primary, fenfluramine-associated (1 variants)
  • Drug- or toxin-induced pulmonary arterial hypertension;Pulmonary arterial hypertension (1 variants)
  • Idiopathic and/or familial pulmonary arterial hypertension (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BMPR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
5
clinvar
82
clinvar
5
clinvar
92
missense
10
clinvar
10
clinvar
67
clinvar
44
clinvar
15
clinvar
146
nonsense
30
clinvar
5
clinvar
35
start loss
0
frameshift
57
clinvar
4
clinvar
1
clinvar
62
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
8
clinvar
7
clinvar
15
splice region
1
6
8
3
18
non coding
97
clinvar
34
clinvar
66
clinvar
197
Total 105 26 171 160 86

Highest pathogenic variant AF is 0.0000131

Variants in BMPR2

This is a list of pathogenic ClinVar variants found in the BMPR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
2-202376361-A-C Pulmonary hypertension, primary, 1 Uncertain significance (Jan 13, 2018)333616
2-202376446-G-A Pulmonary hypertension, primary, 1 Uncertain significance (Jan 12, 2018)896766
2-202376511-AGGC-A Pulmonary hypertension, primary, 1 Uncertain significance (Jun 14, 2016)333618
2-202376511-AGGCGGCGGC-A BMPR2-related condition Benign (Feb 20, 2019)3041823
2-202376511-AGGCGGCGGCGGC-A BMPR2-related condition Likely benign (Mar 27, 2019)3049579
2-202376511-A-AGGC Pulmonary hypertension, primary, 1 Benign/Likely benign (Nov 20, 2020)333617
2-202376511-A-AGGCGGC Likely benign (May 28, 2021)1707255
2-202376511-A-AGGCGGCGGC Benign (Dec 10, 2019)1238911
2-202376511-A-AGGCGGCGGCGGC Benign (Nov 01, 2022)2651825
2-202376528-GC-AT Pulmonary hypertension, primary, 1 Pathogenic (-)425668
2-202376542-G-A Pulmonary hypertension, primary, 1 Uncertain significance (Jan 13, 2018)333619
2-202376545-G-A Pulmonary hypertension, primary, 1 Uncertain significance (Jan 12, 2018)896767
2-202376545-G-GGCA Pulmonary hypertension, primary, 1 Likely benign (Jun 14, 2016)333620
2-202376548-A-G Pulmonary hypertension, primary, 1 Benign/Likely benign (Jul 07, 2018)333622
2-202376548-AGCA-GGCGGCGGCGGCG Pulmonary hypertension, primary, 1 Uncertain significance (Jun 14, 2016)333621
2-202376551-A-G Pulmonary hypertension, primary, 1 Conflicting classifications of pathogenicity (Jul 07, 2018)897238
2-202376553-C-T Pulmonary hypertension, primary, 1 Uncertain significance (Jan 13, 2018)333623
2-202376554-A-G Likely benign (Jul 07, 2018)1203518
2-202376604-G-A Pulmonary hypertension, primary, 1 Uncertain significance (Jan 13, 2018)333624
2-202376638-G-T Pulmonary hypertension, primary, 1 Uncertain significance (Jan 13, 2018)333625
2-202376722-C-T Pulmonary hypertension, primary, 1 Uncertain significance (Jan 12, 2018)333626
2-202376771-C-G Pulmonary hypertension, primary, 1 Benign (Jan 13, 2018)333627
2-202376773-C-T Pulmonary hypertension, primary, 1 Uncertain significance (Jan 13, 2018)333628
2-202376806-G-A Pulmonary hypertension, primary, 1 • Pulmonary hypertension, primary, 1;Pulmonary venoocclusive disease 1 • Primary pulmonary hypertension • not specified Benign/Likely benign (Jun 28, 2023)333629
2-202376881-A-G Pulmonary hypertension, primary, 1 • Primary pulmonary hypertension Uncertain significance (Apr 13, 2022)333630

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BMPR2protein_codingprotein_codingENST00000374580 13190816
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.000.0000215125739091257480.0000358
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.064295670.7560.00002986810
Missense in Polyphen110211.730.519542568
Synonymous1.921652000.8270.000009922054
Loss of Function5.88447.90.08350.00000289525

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00007040.0000703
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: 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. 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. {ECO:0000250|UniProtKB:O35607}.;
Disease
DISEASE: Pulmonary venoocclusive disease 1, autosomal dominant (PVOD1) [MIM:265450]: A disease characterized by widespread fibrous obstruction and intimal thickening of septal veins and preseptal venules, a low diffusing capacity for carbon monoxide, occult alveolar hemorrhage, and nodular ground-glass opacities, septal lines and lymph node enlargement showed by high-resolution computed tomography of the chest. It is frequently associated with pulmonary capillary dilatation and proliferation, and is a rare and devastating cause of pulmonary hypertension. {ECO:0000269|PubMed:12446270, ECO:0000269|PubMed:16429395}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
TGF-beta signaling pathway - Homo sapiens (human);Axon guidance - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);TGF-Core;Bone Morphogenic Protein (BMP) Signalling and Regulation;Heart Development;Mesodermal Commitment Pathway;Canonical and Non-Canonical TGF-B signaling;ESC Pluripotency Pathways;Signal Transduction;alk in cardiac myocytes;BMP2 signaling TAK1;TGF-beta super family signaling pathway canonical;IL-7 signaling;BMP receptor signaling;BMP Signalling Pathway;JAK STAT pathway and regulation;EPO signaling;BMP2 signaling TGF-beta MV;VEGF;Signaling by BMP;Signaling by TGF-beta family members;BMP signaling Dro;ALK1 signaling events;ALK2 signaling events (Consensus)

Recessive Scores

pRec
0.501

Intolerance Scores

loftool
0.0515
rvis_EVS
-0.93
rvis_percentile_EVS
9.61

Haploinsufficiency Scores

pHI
0.853
hipred
Y
hipred_score
0.749
ghis
0.601

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.998

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Bmpr2
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name
bmpr2b
Affected structure
thoracic duct
Phenotype tag
abnormal
Phenotype quality
has fewer parts of type

Gene ontology

Biological process
mesoderm formation;maternal placenta development;endothelial cell proliferation;positive regulation of endothelial cell proliferation;lymphangiogenesis;blood vessel remodeling;chondrocyte development;negative regulation of systemic arterial blood pressure;outflow tract septum morphogenesis;outflow tract morphogenesis;atrioventricular valve morphogenesis;mitral valve morphogenesis;tricuspid valve morphogenesis;endocardial cushion development;negative regulation of cell proliferation involved in heart valve morphogenesis;transcription by RNA polymerase II;protein phosphorylation;transmembrane receptor protein serine/threonine kinase signaling pathway;transforming growth factor beta receptor signaling pathway;pattern specification process;brain development;cellular response to starvation;anterior/posterior pattern specification;positive regulation of endothelial cell migration;positive regulation of epithelial cell migration;positive regulation of pathway-restricted SMAD protein phosphorylation;regulation of lung blood pressure;proteoglycan biosynthetic process;negative regulation of cell growth;positive regulation of bone mineralization;BMP signaling pathway;positive regulation of BMP signaling pathway;activin receptor signaling pathway;regulation of cell population proliferation;positive regulation of osteoblast differentiation;positive regulation of ossification;negative regulation of vasoconstriction;positive regulation of transcription by RNA polymerase II;lung alveolus development;cardiac muscle tissue development;positive regulation of axon extension involved in axon guidance;limb development;endochondral bone morphogenesis;ventricular septum morphogenesis;atrial septum morphogenesis;lymphatic endothelial cell differentiation;artery development;venous blood vessel development;positive regulation of cartilage development;retina vasculature development in camera-type eye;pharyngeal arch artery morphogenesis;cellular response to BMP stimulus;endothelial cell apoptotic process;negative regulation of chondrocyte proliferation;semi-lunar valve development;negative regulation of DNA biosynthetic process
Cellular component
extracellular space;nucleoplasm;cytoplasm;plasma membrane;integral component of plasma membrane;caveola;cell-cell adherens junction;basal plasma membrane;cell surface;postsynaptic density;apical plasma membrane;dendrite;neuronal cell body;receptor complex;spanning component of plasma membrane
Molecular function
transforming growth factor beta-activated receptor activity;transforming growth factor beta receptor activity, type II;protein binding;ATP binding;activin receptor activity, type II;growth factor binding;BMP binding;SMAD binding;metal ion binding;BMP receptor activity