Drug- or toxin-induced pulmonary arterial hypertension

Summary

Drug- or toxin-induced pulmonary arterial hypertension (MONDO:0017149) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 1 000 000 (France) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		France	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	drug- or toxin-induced pulmonary arterial hypertension
Mondo ID	MONDO:0017149
EFO	EFO:0009192
Orphanet	275786
UMLS	C0340544
MedGen	573792
GARD	0021026
Is cancer (heuristic)	no

Also known as: drug- or toxin-induced PAH

Data availability: 2 ClinVar variants.

Disease family

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

Related subtypes (4): idiopathic pulmonary arterial hypertension, heritable pulmonary arterial hypertension, pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis, Eisenmenger syndrome

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

2 retrieved; paginated sample, class counts are floors:

1 not provided, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1339375	NM_001204.7(BMPR2):c.419-1G>T	BMPR2	Likely pathogenic	criteria provided, single submitter
1339361	NM_001204.7(BMPR2):c.2457_2464del (p.Ala820fs)	BMPR2	not provided	no classification provided

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

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: 0.