Pulmonary hypertension

Summary

Pulmonary hypertension (MONDO:0005149) is a disease (an umbrella term covering 6 Mondo subtypes) with 1 cohort gene and 656 clinical trials. Top therapeutic interventions include sildenafil, treprostinil, and bosentan.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 656

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pulmonary hypertension
Mondo ID	MONDO:0005149
MeSH	D006976
DOID	DOID:6432
ICD-11	1496633964
SNOMED CT	70995007
UMLS	C0020542
MedGen	9376
GARD	0027347
MedDRA	10037400
Anatomy (UBERON)	UBERON:0002012
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 3 cell lines.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › hypertensive disorder › pulmonary hypertension

Related subtypes (11): essential hypertension, secondary hypertension, early onset hypertension, chemotherapy-induced hypertension, intracranial hypertension, malignant hypertension, ocular hypertension, kallikrein hypertension, hypertension, pregnancy-induced, resistant hypertension, hypertensive urgency

Subtypes (6): Braddock syndrome, chronic thromboembolic pulmonary hypertension, hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome, pulmonary arterial hypertension, pulmonary hypertension owing to lung disease and/or hypoxia, pulmonary hypertension, neonatal

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3384052	NM_001204.7(BMPR2):c.967+1G>T	BMPR2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMPR2	Orphanet:275777	Heritable pulmonary arterial hypertension
BMPR2	Orphanet:275786	Drug- or toxin-induced pulmonary arterial hypertension
BMPR2	Orphanet:31837	Pulmonary venoocclusive disease

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMPR2	HGNC:1078	ENSG00000204217	Q13873	Bone morphogenetic protein receptor type-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMPR2	Bone morphogenetic protein receptor type-2	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMPR2	Kinase	yes		TGFB_receptor, Activin_recp, Prot_kinase_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower lobe of lung	1
tendon of biceps brachii	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMPR2	271	ubiquitous	marker	visceral pleura, lower lobe of lung, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMPR2	3,152

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMPR2	Q13873	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by BMP	1	356.9×	0.008	BMPR2
Signaling by TGFB family members	1	115.3×	0.013	BMPR2
Signal Transduction	1	10.2×	0.098	BMPR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
semi-lunar valve development	1	16852.0×	0.002	BMPR2
obsolete negative regulation of cell proliferation involved in heart valve morphogenesis	1	8426.0×	0.002	BMPR2
regulation of lung blood pressure	1	8426.0×	0.002	BMPR2
pulmonary valve development	1	4213.0×	0.002	BMPR2
endochondral bone morphogenesis	1	4213.0×	0.002	BMPR2
negative regulation of chondrocyte proliferation	1	4213.0×	0.002	BMPR2
aortic valve development	1	3370.4×	0.002	BMPR2
tricuspid valve morphogenesis	1	3370.4×	0.002	BMPR2
venous blood vessel development	1	3370.4×	0.002	BMPR2
positive regulation of axon extension involved in axon guidance	1	2407.4×	0.002	BMPR2
lymphatic endothelial cell differentiation	1	2407.4×	0.002	BMPR2
mitral valve morphogenesis	1	1685.2×	0.002	BMPR2
negative regulation of vasoconstriction	1	1685.2×	0.002	BMPR2
negative regulation of muscle cell differentiation	1	1685.2×	0.002	BMPR2
retina vasculature development in camera-type eye	1	1685.2×	0.002	BMPR2
maternal placenta development	1	1532.0×	0.002	BMPR2
lung vasculature development	1	1532.0×	0.002	BMPR2
endocardial cushion development	1	1404.3×	0.002	BMPR2
artery development	1	1404.3×	0.002	BMPR2
atrial septum morphogenesis	1	1296.3×	0.002	BMPR2
endothelial cell apoptotic process	1	1296.3×	0.002	BMPR2
lymphangiogenesis	1	1203.7×	0.002	BMPR2
negative regulation of systemic arterial blood pressure	1	1053.2×	0.002	BMPR2
chondrocyte development	1	936.2×	0.002	BMPR2
positive regulation of ossification	1	936.2×	0.002	BMPR2
positive regulation of cartilage development	1	936.2×	0.002	BMPR2
proteoglycan biosynthetic process	1	842.6×	0.003	BMPR2
cell surface receptor protein serine/threonine kinase signaling pathway	1	732.7×	0.003	BMPR2
negative regulation of smooth muscle cell proliferation	1	624.1×	0.003	BMPR2
cellular response to BMP stimulus	1	561.7×	0.003	BMPR2

Therapeutics

Drugs indicated for this disease

9 approved, 14 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ambrisentan	Approved (phase 4)
Bosentan	Approved (phase 4)
Iloprost	Approved (phase 4)
Macitentan	Approved (phase 4)
Nitric Oxide	Approved (phase 4)
Riociguat	Approved (phase 4)
Selexipag	Approved (phase 4)
Tadalafil	Approved (phase 4)
Treprostinil	Approved (phase 4)
Albuterol	Phase 3 (in late-stage trials)
Bardoxolone Methyl	Phase 3 (in late-stage trials)
Epoprostenol	Phase 3 (in late-stage trials)
Escitalopram	Phase 3 (in late-stage trials)
Imatinib	Phase 3 (in late-stage trials)
Losartan	Phase 3 (in late-stage trials)
Nifedipine	Phase 3 (in late-stage trials)
Oxygen	Phase 3 (in late-stage trials)
Sacubitril	Phase 3 (in late-stage trials)
Seralutinib	Phase 3 (in late-stage trials)
Sildenafil	Phase 3 (in late-stage trials)
Sitaxentan	Phase 3 (in late-stage trials)
Valsartan	Phase 3 (in late-stage trials)
Vardenafil	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Capsaicin, Carvedilol, Dexmedetomidine, Milrinone, Simvastatin, Sodium Chloride, Sulfur Hexafluoride, Vasopressin, Warfarin.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BMPR2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPR2	19	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	BMPR2
RUXOLITINIB	4	BMPR2
BOSUTINIB	4	BMPR2
DEUCRAVACITINIB	4	BMPR2
NINTEDANIB	4	BMPR2
SUNITINIB	4	BMPR2
LINIFANIB	3	BMPR2
ORANTINIB	3	BMPR2
DOVITINIB	3	BMPR2
LESTAURTINIB	3	BMPR2
SILMITASERTIB	2	BMPR2
SU-014813	2	BMPR2
OSI-027	2	BMPR2
AT-9283	2	BMPR2
TOZASERTIB	2	BMPR2
KW-2449	1	BMPR2
RGB-286638	1	BMPR2
PF-03814735	1	BMPR2
CYC-116	1	BMPR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BMPR2	166	Binding:165, ADMET:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BMPR2	166

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

19 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	BMPR2
RUXOLITINIB	4	BMPR2
BOSUTINIB	4	BMPR2
DEUCRAVACITINIB	4	BMPR2
NINTEDANIB	4	BMPR2
SUNITINIB	4	BMPR2
LINIFANIB	3	BMPR2
ORANTINIB	3	BMPR2
DOVITINIB	3	BMPR2
LESTAURTINIB	3	BMPR2
SILMITASERTIB	2	BMPR2
SU-014813	2	BMPR2
OSI-027	2	BMPR2
AT-9283	2	BMPR2
TOZASERTIB	2	BMPR2
KW-2449	1	BMPR2
RGB-286638	1	BMPR2
PF-03814735	1	BMPR2
CYC-116	1	BMPR2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BMPR2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 656.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	411
PHASE2	79
PHASE3	63
PHASE4	34
PHASE1	29
PHASE1/PHASE2	18
PHASE2/PHASE3	16
EARLY_PHASE1	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03581877	PHASE4	ACTIVE_NOT_RECRUITING	Peripheral Systemic Thrombolysis Versus Catheter Directed Thrombolysis for Submassive PE
NCT07247240	PHASE4	NOT_YET_RECRUITING	Efficacy of Inhaled Nitric Oxide in Congenital Diaphragmatic Hernia
NCT07359599	PHASE4	RECRUITING	The Impact of IV Iron on Exercise Capacity and Quality of Life in Pulmonary Hypertension
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00075179	PHASE4	TERMINATED	Natrecor in Pulmonary Hypertension
NCT00205426	PHASE4	COMPLETED	Natrecor for Pulmonary Hypertension in Lung Transplants
NCT00373360	PHASE4	COMPLETED	Safety, Efficacy and Treatment Satisfaction in Patients With PAH Rapidly Switched From Epoprostenol to Remodulin
NCT00409526	PHASE4	TERMINATED	Inhaled Iloprost for the Treatment of Persistent Pulmonary Hypertension in the Term and Near Term Infants.
NCT00491803	PHASE4	COMPLETED	Sildenafil Effects on Pulmonary Haemodynamics and Gas Exchange in Chronic Obstructive Pulmonary Disease (COPD)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00637065	PHASE4	UNKNOWN	Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
NCT00679068	PHASE4	TERMINATED	Effects of Bosentan on Respiratory Mechanics
NCT00730067	PHASE4	WITHDRAWN	Sildenafil for Chronic Obstructive Pulmonary Disease (COPD) Associated Pulmonary Hypertension
NCT00840463	PHASE4	TERMINATED	Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan
NCT00862043	PHASE4	COMPLETED	Sildenafil for Secondary Pulmonary Hypertension Due to Valvular Disease
NCT00878878	PHASE4	COMPLETED	Evaluate Effect of Optison on Pulmonary Artery Systolic Pressure (PASP) and Pulmonary Vascular Resistance (PVR).
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01051960	PHASE4	COMPLETED	Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
NCT01055405	PHASE4	COMPLETED	Study of Sildenafil Effects in Combination With Rehabilitation in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Associated Pulmonary Hypertension
NCT01468571	PHASE4	UNKNOWN	Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension
NCT01839110	PHASE4	COMPLETED	Targeting the Right Ventricle in Pulmonary Hypertension
NCT02050230	PHASE4	TERMINATED	Hemodynamic Effects of Stored Blood Transfusion in Intensive Care Patients
NCT02053246	PHASE4	TERMINATED	Improving Treatment Personalization of Pulmonary Hypertension Associated With Diastolic Heart Failure
NCT02133352	PHASE4	COMPLETED	Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction
NCT02170519	PHASE4	TERMINATED	Inhaled Aerosolized Prostacyclin for Pulmonary Hypertension Requiring Inhaled Nitric Oxide
NCT02378649	PHASE4	COMPLETED	PDEI Following Mitral Valve Surgery in Patients With Pulmonary Hypertension
NCT02742909	PHASE4	COMPLETED	Acute Effects of rhBNP in Patients With PH Associated With Acute Exacerbation of Chronic Pulmonary Disease
NCT02829034	PHASE4	COMPLETED	Targeting Right Ventricle in Pulmonary Hypertension Gilead
NCT03044314	PHASE4	TERMINATED	Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension
NCT03309592	PHASE4	WITHDRAWN	Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension
NCT03809156	PHASE4	UNKNOWN	Upfront Combination Pulmonary Arterial Hypertension Therapy
NCT03835676	PHASE4	UNKNOWN	Effects of Treprostinil on Right Ventricular Structure and Function in Patients With Pulmonary Arterial Hypertension
NCT04231084	PHASE4	COMPLETED	Comparison of Vasodilator Response of Inhaled Epoprostenol and Inhaled Nitric Oxide
NCT06605326	PHASE4	COMPLETED	Subcutaneous Treprostinil as a Bridge to Lung Transplantation in Severe Pulmonary Hypertension: A Single-Arm Retrospective Study
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT05473520	PHASE3	RECRUITING	Doxycycline Host-directed Therapy to Improve Lung Function and Decrease Tissue Destruction in Pulmonary Tuberculosis
NCT05824923	PHASE3	RECRUITING	A Trial to Evaluate the Safety and Efficacy of Pulmonary Artery Denervation for the Treatment of Pulmonary Hypertension Associated With Left Heart Failure
NCT05844462	PHASE3	RECRUITING	Tadalafil for Severe Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease
NCT05983250	PHASE3	RECRUITING	LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF
NCT07179380	PHASE3	RECRUITING	Efficacy and Safety Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SILDENAFIL	4	55
TREPROSTINIL	4	36
BOSENTAN	4	15
ILOPROST	4	14
AMBRISENTAN	4	13
TADALAFIL	4	7
SITAXENTAN	4	6
NITRIC OXIDE	4	5
MILRINONE	4	4
RANOLAZINE	4	4
WATER	4	4
HYDROXYUREA	4	3
MACITENTAN	4	3
ALPROSTADIL	4	2
CAPSAICIN	4	2
LOSARTAN	4	2
NESIRITIDE	4	2
NITROUS ACID	4	2
VASOPRESSIN	4	2
ACETAZOLAMIDE	4	1
ALTEPLASE	4	1
CONIVAPTAN	4	1
DEXTROSE	4	1
EPOPROSTENOL	4	1
ETOMIDATE	4	1
FLUDEOXYGLUCOSE	4	1
GLUTAMINE	4	1
IRON SUCROSE	4	1
KETAMINE HYDROCHLORIDE	4	1
MELATONIN	4	1