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

ENSG00000204217 ∙ NCBI:659 ∙ OMIM:600799 ∙ HGNC:1078 ∙ Uniprot:Q13873 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary hypertension, primary 1; Pulmonary venoocclusive disease 1	AD	Cardiovascular; Pharmacogenomic; Pulmonary	While 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 disease	Cardiovascular; Pulmonary	601742; 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	82	5	92
missense	10	10	67	44	15	146
nonsense	30	5				35
start loss						0
frameshift	57	4	1			62
inframe indel			1			1
splice donor/acceptor (+/-2bp)	8	7				15
splice region	1		6	8	3	18
non coding			97	34	66	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)
2-202376446-G-A		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 12, 2018)
2-202376511-AGGC-A		Pulmonary hypertension, primary, 1	Uncertain significance (Jun 14, 2016)
2-202376511-AGGCGGCGGC-A		BMPR2-related disorder	Benign (Feb 20, 2019)
2-202376511-AGGCGGCGGCGGC-A		BMPR2-related disorder	Likely benign (Mar 27, 2019)
2-202376511-A-AGGC		Pulmonary hypertension, primary, 1	Benign/Likely benign (Nov 20, 2020)
2-202376511-A-AGGCGGC			Likely benign (May 28, 2021)
2-202376511-A-AGGCGGCGGC			Benign (Dec 10, 2019)
2-202376511-A-AGGCGGCGGCGGC			Benign (Nov 01, 2022)
2-202376528-GC-AT		Pulmonary hypertension, primary, 1	Pathogenic (-)
2-202376542-G-A		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 13, 2018)
2-202376545-G-A		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 12, 2018)
2-202376545-G-GGCA		Pulmonary hypertension, primary, 1	Likely benign (Jun 14, 2016)
2-202376548-A-G		Pulmonary hypertension, primary, 1	Benign/Likely benign (Jul 07, 2018)
2-202376548-AGCA-GGCGGCGGCGGCG		Pulmonary hypertension, primary, 1	Uncertain significance (Jun 14, 2016)
2-202376551-A-G		Pulmonary hypertension, primary, 1 • Pulmonary arterial hypertension	Benign (May 03, 2024)
2-202376553-C-T		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 13, 2018)
2-202376554-A-G			Likely benign (Jul 07, 2018)
2-202376604-G-A		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 13, 2018)
2-202376638-G-T		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 13, 2018)
2-202376722-C-T		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 12, 2018)
2-202376771-C-G		Pulmonary hypertension, primary, 1	Benign (Jan 13, 2018)
2-202376773-C-T		Pulmonary hypertension, primary, 1	Uncertain significance (Jan 13, 2018)
2-202376806-G-A		Pulmonary hypertension, primary, 1 • Primary pulmonary hypertension • not specified • Pulmonary hypertension, primary, 1;Pulmonary venoocclusive disease 1 • Pulmonary arterial hypertension	Benign (May 01, 2024)
2-202376881-A-G		Pulmonary hypertension, primary, 1 • Primary pulmonary hypertension	Uncertain significance (Apr 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BMPR2	protein_coding	protein_coding	ENST00000374580	13	190816

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000215	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.06	429	567	0.756	0.0000298	6810
Missense in Polyphen		110	211.73	0.51954		2568
Synonymous	1.92	165	200	0.827	0.00000992	2054
Loss of Function	5.88	4	47.9	0.0835	0.00000289	525

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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