Idiopathic pulmonary arterial hypertension

Summary

Idiopathic pulmonary arterial hypertension (MONDO:0001999) is a disease with 1 cohort gene (2 GWAS associations across 8 studies) and 34 clinical trials. Top therapeutic interventions include bisoprolol, riociguat, and benzbromarone.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• GWAS associations: 2
• ClinVar variants: 1
• Phenotypes (HPO): 18
• Clinical trials: 34

Clinical features

Epidemiology

Prevalence records

16 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Worldwide	Validated
Point prevalence	1-9 / 100 000	1.1	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.1	France	Validated
Annual incidence	1-9 / 1 000 000	0.12	Spain	Validated
Annual incidence	1-9 / 1 000 000	0.62	Czech Republic	Validated
Annual incidence	1-9 / 1 000 000	0.12	Switzerland	Validated
Annual incidence	1-9 / 1 000 000	0.25	United Kingdom	Validated
Annual incidence	1-9 / 1 000 000	0.11	United States	Validated
Annual incidence	1-9 / 1 000 000	0.17	Belgium	Validated
Annual incidence	1-9 / 1 000 000	0.14	Israel	Validated
Point prevalence	1-9 / 1 000 000	0.59	France	Validated
Point prevalence	1-9 / 1 000 000	0.56	Spain	Validated
Point prevalence	1-9 / 100 000	1.4	Czech Republic	Validated
Point prevalence	1-9 / 1 000 000	0.86	Switzerland	Validated
Point prevalence	1-9 / 100 000	1.7	United Kingdom	Validated
Point prevalence	1-9 / 1 000 000	0.8	Israel	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0002094	Dyspnea	Obligate (100%)
HP:0001667	Right ventricular hypertrophy	Very frequent (80-99%)
HP:0002092	Pulmonary arterial hypertension	Very frequent (80-99%)
HP:0004890	Elevated pulmonary artery pressure	Very frequent (80-99%)
HP:0005317	Increased pulmonary vascular resistance	Very frequent (80-99%)
HP:3000042	Abnormal jugular vein morphology	Very frequent (80-99%)
HP:0001279	Syncope	Frequent (30-79%)
HP:0001635	Congestive heart failure	Frequent (30-79%)
HP:0001785	Ankle swelling	Frequent (30-79%)
HP:0005180	Tricuspid regurgitation	Frequent (30-79%)
HP:0012098	Edema of the dorsum of feet	Frequent (30-79%)
HP:0030148	Heart murmur	Frequent (30-79%)
HP:0100749	Chest pain	Frequent (30-79%)
HP:0001962	Palpitations	Occasional (5-29%)
HP:0002105	Hemoptysis	Occasional (5-29%)
HP:0010741	Pedal edema	Occasional (5-29%)
HP:0003549	Abnormality of connective tissue	Excluded (0%)
HP:0004870	Chronic hemolytic anemia	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic pulmonary arterial hypertension
Mondo ID	MONDO:0001999
Orphanet	275766
DOID	DOID:14557
ICD-10-CM	I27.0
ICD-11	265520344
SNOMED CT	697898008
UMLS	C3203102
MedGen	468368
GARD	0027594
MedDRA	10065151
Is cancer (heuristic)	no

Also known as: idiopathic pulmonary arterial hypertension · IPAH · primary pulmonary arterial hypertension · primary pulmonary hypertension

Data availability: 1 ClinVar variant · 2 GWAS associations (8 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart failure › congestive heart failure › cor pulmonale › chronic pulmonary heart disease › idiopathic pulmonary arterial hypertension

Related subtypes (1): kyphoscoliotic heart disease

Genetics & variants

GWAS landscape

2 GWAS associations across 8 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs554564741	6e-12	RGS3 - C14orf119P1	C	2.4
rs182134725	4e-08	PLPPR5, PLPPR5-AS1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477880	Verma A	2024	1,745	446,529	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477879	Verma A	2024	608	120,361	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480139	Verma A	2024	608	120,361	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079985	Backman JD	2021	525	387,405	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083971	Backman JD	2021	525	387,405	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436085	Zhou W	2018	446	402,375	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651666	Liu TY	2025	373	233,745	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90043961	Jiang L	2021	99	456,249	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	1

Functional consequences

Consequence	Count
regulatory_region_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs554564741	9	113625229	C>G,T	0.001	regulatory_region_variant	RGS3 - C14orf119P1	6e-12	Tier 3: regulatory
rs182134725	1	99073064	G>A		intron_variant	PLPPR5, PLPPR5-AS1	4e-08	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
906582	NM_001203.3(BMPR1B):c.11G>A (p.Arg4Gln)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMPR1B	Orphanet:2098	Acromesomelic dysplasia, Grebe type
BMPR1B	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
BMPR1B	Orphanet:93384	Brachydactyly type C
BMPR1B	Orphanet:93388	Brachydactyly type A1
BMPR1B	Orphanet:93396	Brachydactyly type A2

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
BMPR1B	HGNC:1077	ENSG00000138696	O00238	Bone morphogenetic protein receptor type-1B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMPR1B	Bone morphogenetic protein receptor type-1B	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)
BMPR1B	Kinase	yes	2.7.10.2	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
bronchial epithelial cell	1
calcaneal tendon	1
cauda epididymis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMPR1B	239	broad	marker	calcaneal tendon, bronchial epithelial cell, cauda epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMPR1B	116

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMPR1B	O00238	1

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	BMPR1B
Signaling by TGFB family members	1	115.3×	0.013	BMPR1B
Signal Transduction	1	10.2×	0.098	BMPR1B

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
ovarian cumulus expansion	1	4213.0×	0.002	BMPR1B
endochondral bone morphogenesis	1	4213.0×	0.002	BMPR1B
negative regulation of chondrocyte proliferation	1	4213.0×	0.002	BMPR1B
ovulation cycle	1	2407.4×	0.003	BMPR1B
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	1404.3×	0.003	BMPR1B
chondrocyte development	1	936.2×	0.003	BMPR1B
positive regulation of cartilage development	1	936.2×	0.003	BMPR1B
proteoglycan biosynthetic process	1	842.6×	0.003	BMPR1B
positive regulation of chondrocyte differentiation	1	802.5×	0.003	BMPR1B
cartilage condensation	1	766.0×	0.003	BMPR1B
retinal ganglion cell axon guidance	1	766.0×	0.003	BMPR1B
central nervous system neuron differentiation	1	601.9×	0.004	BMPR1B
cellular response to BMP stimulus	1	561.7×	0.004	BMPR1B
dorsal/ventral pattern formation	1	421.3×	0.004	BMPR1B
positive regulation of bone mineralization	1	391.9×	0.004	BMPR1B
eye development	1	351.1×	0.005	BMPR1B
cellular response to growth factor stimulus	1	318.0×	0.005	BMPR1B
retina development in camera-type eye	1	255.3×	0.006	BMPR1B
positive regulation of osteoblast differentiation	1	224.7×	0.006	BMPR1B
BMP signaling pathway	1	200.6×	0.006	BMPR1B
MAPK cascade	1	153.2×	0.008	BMPR1B
osteoblast differentiation	1	121.2×	0.010	BMPR1B
positive regulation of gene expression	1	38.7×	0.029	BMPR1B
inflammatory response	1	37.7×	0.029	BMPR1B
cell differentiation	1	29.1×	0.036	BMPR1B
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	BMPR1B

Therapeutics

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
BMPR1B	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPR1B	28	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	BMPR1B
FEDRATINIB	4	BMPR1B
AXITINIB	4	BMPR1B
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B
SUNITINIB	4	BMPR1B
DASATINIB	4	BMPR1B
QUIZARTINIB	4	BMPR1B
CRIZOTINIB	4	BMPR1B
SARACATINIB	3	BMPR1B
LINIFANIB	3	BMPR1B
CANERTINIB	3	BMPR1B
ALVOCIDIB	3	BMPR1B
LESTAURTINIB	3	BMPR1B
SU-014813	2	BMPR1B
R-406	2	BMPR1B
AT-9283	2	BMPR1B
ZILURGISERTIB	2	BMPR1B
TOZASERTIB	2	BMPR1B
KER-047	2	BMPR1B
TAK-285	1	BMPR1B
KW-2449	1	BMPR1B
MLN-8054	1	BMPR1B
XL-228	1	BMPR1B
ASP-3026	1	BMPR1B
AEW-541	1	BMPR1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BMPR1B	166	Binding:164, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMPR1B	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BMPR1B	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

28 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)
MOMELOTINIB	4	BMPR1B
FEDRATINIB	4	BMPR1B
AXITINIB	4	BMPR1B
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B
SUNITINIB	4	BMPR1B
DASATINIB	4	BMPR1B
QUIZARTINIB	4	BMPR1B
CRIZOTINIB	4	BMPR1B
SARACATINIB	3	BMPR1B
LINIFANIB	3	BMPR1B
CANERTINIB	3	BMPR1B
ALVOCIDIB	3	BMPR1B
LESTAURTINIB	3	BMPR1B
SU-014813	2	BMPR1B
R-406	2	BMPR1B
AT-9283	2	BMPR1B
ZILURGISERTIB	2	BMPR1B
TOZASERTIB	2	BMPR1B
KER-047	2	BMPR1B
TAK-285	1	BMPR1B
KW-2449	1	BMPR1B
MLN-8054	1	BMPR1B
XL-228	1	BMPR1B
ASP-3026	1	BMPR1B
AEW-541	1	BMPR1B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BMPR1B
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: 34.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	17
PHASE3	6
PHASE2	5
PHASE4	2
PHASE1	2
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01288651	PHASE4	UNKNOWN	Iron Deficiency In Pulmonary Hypertension
NCT04954742	PHASE4	TERMINATED	Effects of Riociguat on RIght VEntricular Size and Function in PAH and CTEPH
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
NCT03992755	PHASE3	ACTIVE_NOT_RECRUITING	Extension Study for Participants in LIQ861 Trials to Evaluate the Long-term Safety of Dry Powder Inhalation of Treprostinil
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT03399604	PHASE3	COMPLETED	Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01246037	PHASE1/PHASE2	UNKNOWN	Beta-blockers in i-PAH
NCT02790450	PHASE2	COMPLETED	Acute Effects of Benzbromaron on the Pulmonary Circulation
NCT03528902	PHASE2	COMPLETED	Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension
NCT05339087	PHASE2	TERMINATED	Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH
NCT05493371	PHASE2	COMPLETED	Empagliflozin in Pulmonary Arterial Hypertension
NCT01590108	PHASE1	COMPLETED	The Study of Apelin-APJ System on Pulmonary Hypertension Patients and Healthy Subjects
NCT04908397	PHASE1	COMPLETED	Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension
NCT01683981	EARLY_PHASE1	UNKNOWN	Exercise Capacity and Quality of Life in Patients With PPH Receiving Short Term Oral L-Citrulline Malate
NCT01884051	Not specified	RECRUITING	Hormonal, Metabolic, and Signaling Interactions in PAH
NCT05462574	Not specified	RECRUITING	Right Ventricle Lipid in Pulmonary Arterial Hypertension (PAH)
NCT05584722	Not specified	RECRUITING	Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals
NCT06587074	Not specified	ACTIVE_NOT_RECRUITING	Features of the Clinical Course and Prognosis in Patients With Idiopathic Pulmonary Hypertension When Using Modern Strategies of Specific Therapy
NCT07558460	Not specified	ENROLLING_BY_INVITATION	Virtual Reality in Patients With Pulmonary Hypertension: A Randomized Controlled Trial
NCT00257413	Not specified	COMPLETED	Safety and Efficacy Study of Transplantation of EPCs to Treat Idiopathic Pulmonary Arterial Hypertension
NCT00372346	Not specified	UNKNOWN	Safety and Efficacy Study of Transplantation of EPCs to Treat Idiopathic Pulmonary Arterial Hypertension
NCT00641836	Not specified	COMPLETED	Safety and Feasibility of Autologous Endothelial Progenitor Cells Transplantation in Patients With Idiopathic Pulmonary Arterial Hypertension
NCT00722254	Not specified	TERMINATED	Reversible Secondary Myelofibrosis or Clonal Myeloproliferative Disorder
NCT01613287	Not specified	COMPLETED	Proof of Concept Study of IMMUNOadsorption Therapy in Patients With Idiopathic Pulmonary Arterial Hypertension
NCT01645826	Not specified	WITHDRAWN	Efficacy Study of Cardizem in Pulmonary Arterial Hypertension
NCT02565030	Not specified	COMPLETED	Chronic Thrombo-embolic Pulmonary Hypertension: Classification and Long Term Outcome
NCT02859194	Not specified	COMPLETED	The Effect of Lt to Rt Shunt Using Veno-veno-arterial Extracorporeal Membrane Oxygenation (ECMO) on Coronary Oxygenation in Lung Transplantation Patients
NCT02959723	Not specified	UNKNOWN	Physiopathology of Pulmonary Arterial Hypertension: Mechanistic Studies
NCT03069716	Not specified	COMPLETED	A Mobile Health Intervention in Pulmonary Arterial Hypertension
NCT03933579	Not specified	UNKNOWN	The PAH Platform for Deep Phenotyping in Korean Subjects
NCT05767918	Not specified	COMPLETED	StratosPHere (Non-interventional Study)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BISOPROLOL	4	3
RIOCIGUAT	4	2
BENZBROMARONE	4	1
DILTIAZEM HYDROCHLORIDE	4	1
LEVOCARNITINE	4	1
OXYGEN	4	1
RALINEPAG	3	3
CITRULLINE MALATE	0	1