Pulmonary venoocclusive disease 1

Summary

Pulmonary venoocclusive disease 1 (MONDO:0020713) is a disease caused by BMPR2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: BMPR2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 167

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pulmonary venoocclusive disease 1
Mondo ID	MONDO:0020713
OMIM	265450
DOID	DOID:0081268
UMLS	C3887658
MedGen	854500
GARD	0025220
Is cancer (heuristic)	no

Also known as: pulmonary venoocclusive disease 1, autosomal dominant · PVOD1

Data availability: 167 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › pulmonary venoocclusive disease › pulmonary venoocclusive disease 1

Related subtypes (1): pulmonary venoocclusive disease 2

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

167 retrieved; paginated sample, class counts are floors:

93 uncertain significance, 26 conflicting classifications of pathogenicity, 18 pathogenic, 10 likely pathogenic, 8 likely benign, 6 benign/likely benign, 5 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1328388	NM_001204.7(BMPR2):c.530-2A>G	BMPR2	Pathogenic	no assertion criteria provided
1706628	NM_001204.7(BMPR2):c.1169del (p.Gly390fs)	BMPR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222513	NM_001204.7(BMPR2):c.439C>T (p.Arg147Ter)	BMPR2	Pathogenic	criteria provided, multiple submitters, no conflicts
280019	NM_001204.7(BMPR2):c.637C>T (p.Arg213Ter)	BMPR2	Pathogenic	criteria provided, multiple submitters, no conflicts
39423	NM_001204.7(BMPR2):c.583G>T (p.Glu195Ter)	BMPR2	Pathogenic	no assertion criteria provided
409813	NM_001204.7(BMPR2):c.1398G>A (p.Trp466Ter)	BMPR2	Pathogenic	criteria provided, multiple submitters, no conflicts
409826	NM_001204.7(BMPR2):c.961C>T (p.Arg321Ter)	BMPR2	Pathogenic	criteria provided, multiple submitters, no conflicts
409829	NM_001204.7(BMPR2):c.968-5A>G	BMPR2	Pathogenic	reviewed by expert panel
425700	NM_001204.7(BMPR2):c.88C>T (p.Gln30Ter)	BMPR2	Pathogenic	criteria provided, single submitter
425708	NM_001204.7(BMPR2):c.156_157del (p.Ser52_His53insTer)	BMPR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425875	NM_001204.7(BMPR2):c.1120del (p.Ala373_Ile374insTer)	BMPR2	Pathogenic	no assertion criteria provided
425898	NM_001204.7(BMPR2):c.1241G>A (p.Trp414Ter)	BMPR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425917	NM_001204.7(BMPR2):c.1277-9A>G	BMPR2	Pathogenic	reviewed by expert panel
425965	NM_001204.7(BMPR2):c.1750C>T (p.Arg584Ter)	BMPR2	Pathogenic	criteria provided, single submitter
548686	NM_001204.7(BMPR2):c.529+1G>A	BMPR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8796	NM_001204.7(BMPR2):c.2695C>T (p.Arg899Ter)	BMPR2	Pathogenic	criteria provided, multiple submitters, no conflicts
8802	NM_001204.7(BMPR2):c.1471C>T (p.Arg491Trp)	BMPR2	Pathogenic	criteria provided, multiple submitters, no conflicts
8805	NM_001204.7(BMPR2):c.2617C>T (p.Arg873Ter)	BMPR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8806	NM_001204.7(BMPR2):c.1472G>A (p.Arg491Gln)	BMPR2	Pathogenic	reviewed by expert panel
8812	NM_001204.7(BMPR2):c.631C>T (p.Arg211Ter)	BMPR2	Pathogenic	criteria provided, multiple submitters, no conflicts
8814	NM_001204.7(BMPR2):c.44del (p.Pro15fs)	BMPR2	Pathogenic	criteria provided, single submitter
8815	NM_001204.7(BMPR2):c.120T>G (p.Tyr40Ter)	BMPR2	Pathogenic	no assertion criteria provided
8816	NM_001204.7(BMPR2):c.(76+1_77-1)_(247+1_248-1)del	BMPR2	Pathogenic	no assertion criteria provided
1328389	NM_001204.7(BMPR2):c.2094del (p.Pro698_Leu699insTer)	BMPR2	Likely pathogenic	no assertion criteria provided
1339415	NM_001204.7(BMPR2):c.2073dup (p.Gln692fs)	BMPR2	Likely pathogenic	criteria provided, single submitter
3585263	NM_001204.7(BMPR2):c.878_879del (p.Leu293fs)	BMPR2	Likely pathogenic	criteria provided, single submitter
3585264	NM_001204.7(BMPR2):c.878_880delinsCT (p.Leu293fs)	BMPR2	Likely pathogenic	criteria provided, single submitter
3585278	NM_001204.7(BMPR2):c.1459G>C (p.Asp487His)	BMPR2	Likely pathogenic	criteria provided, single submitter
3585282	NM_001204.7(BMPR2):c.1595C>G (p.Ser532Ter)	BMPR2	Likely pathogenic	criteria provided, single submitter
3764719	NM_001204.7(BMPR2):c.309_310insG (p.Thr104fs)	BMPR2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BMPR2	Definitive	Autosomal dominant	pulmonary hypertension, primary, 1	6

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
EIF2AK4	Orphanet:199241	Pulmonary capillary hemangiomatosis
EIF2AK4	Orphanet:275777	Heritable pulmonary arterial hypertension
EIF2AK4	Orphanet:31837	Pulmonary venoocclusive disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMPR2	HGNC:1078	ENSG00000204217	Q13873	Bone morphogenetic protein receptor type-2	gencc,clinvar
EIF2AK4	HGNC:19687	ENSG00000128829	Q9P2K8	eIF-2-alpha kinase GCN2	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.
EIF2AK4	eIF-2-alpha kinase GCN2	Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability.

Protein-family classification

Druggable: 2 · 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	2	27.7×	0.001

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMPR2	Kinase	yes		TGFB_receptor, Activin_recp, Prot_kinase_dom
EIF2AK4	Kinase	yes		Prot_kinase_dom, RWD_dom, Ser/Thr_kinase_AS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower lobe of lung	1
tendon of biceps brachii	1
visceral pleura	1
adenohypophysis	1
bone marrow cell	1
pituitary gland	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
EIF2AK4	258	ubiquitous	marker	adenohypophysis, pituitary gland, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EIF2AK4	3,193
BMPR2	3,152

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EIF2AK4	Q9P2K8	8
BMPR2	Q13873	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 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	178.4×	0.022	BMPR2
Signaling by TGFB family members	1	57.7×	0.024	BMPR2
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	55.4×	0.024	EIF2AK4
Signal Transduction	1	5.1×	0.187	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of translational initiation by eIF2 alpha phosphorylation	1	8426.0×	0.002	EIF2AK4
viral translation	1	8426.0×	0.002	EIF2AK4
positive regulation of translational initiation in response to starvation	1	8426.0×	0.002	EIF2AK4
semi-lunar valve development	1	8426.0×	0.002	BMPR2
obsolete negative regulation of cell proliferation involved in heart valve morphogenesis	1	4213.0×	0.003	BMPR2
regulation of lung blood pressure	1	4213.0×	0.003	BMPR2
pulmonary valve development	1	2106.5×	0.003	BMPR2
obsolete negative regulation of CREB transcription factor activity	1	2106.5×	0.003	EIF2AK4
endochondral bone morphogenesis	1	2106.5×	0.003	BMPR2
GCN2-mediated signaling	1	2106.5×	0.003	EIF2AK4
negative regulation of chondrocyte proliferation	1	2106.5×	0.003	BMPR2
response to amino acid starvation	1	2106.5×	0.003	EIF2AK4
aortic valve development	1	1685.2×	0.003	BMPR2
tricuspid valve morphogenesis	1	1685.2×	0.003	BMPR2
negative regulation of translational initiation in response to stress	1	1685.2×	0.003	EIF2AK4
venous blood vessel development	1	1685.2×	0.003	BMPR2
positive regulation of axon extension involved in axon guidance	1	1203.7×	0.004	BMPR2
lymphatic endothelial cell differentiation	1	1203.7×	0.004	BMPR2
positive regulation of adaptive immune response	1	1053.2×	0.004	EIF2AK4
regulation of feeding behavior	1	936.2×	0.004	EIF2AK4
mitral valve morphogenesis	1	842.6×	0.004	BMPR2
negative regulation of vasoconstriction	1	842.6×	0.004	BMPR2
negative regulation of muscle cell differentiation	1	842.6×	0.004	BMPR2
retina vasculature development in camera-type eye	1	842.6×	0.004	BMPR2
maternal placenta development	1	766.0×	0.004	BMPR2
host-mediated suppression of viral genome replication	1	766.0×	0.004	EIF2AK4
lung vasculature development	1	766.0×	0.004	BMPR2
endocardial cushion development	1	702.2×	0.004	BMPR2
artery development	1	702.2×	0.004	BMPR2
atrial septum morphogenesis	1	648.1×	0.004	BMPR2

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
EIF2AK4	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPR2	19	4
EIF2AK4	19	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	BMPR2, EIF2AK4
RUXOLITINIB	4	BMPR2
BOSUTINIB	4	BMPR2, EIF2AK4
DEUCRAVACITINIB	4	BMPR2
NINTEDANIB	4	BMPR2, EIF2AK4
SUNITINIB	4	BMPR2, EIF2AK4
NERATINIB	4	EIF2AK4
DASATINIB	4	EIF2AK4
ERLOTINIB	4	EIF2AK4
MIDOSTAURIN	4	EIF2AK4
LINIFANIB	3	BMPR2
ORANTINIB	3	BMPR2
DOVITINIB	3	BMPR2, EIF2AK4
LESTAURTINIB	3	BMPR2, EIF2AK4
MOTESANIB	3	EIF2AK4
SILMITASERTIB	2	BMPR2
SU-014813	2	BMPR2, EIF2AK4
OSI-027	2	BMPR2
AT-9283	2	BMPR2
TOZASERTIB	2	BMPR2, EIF2AK4
R-406	2	EIF2AK4
RAF-265	2	EIF2AK4
PELITINIB	2	EIF2AK4
KW-2449	1	BMPR2, EIF2AK4
RGB-286638	1	BMPR2
PF-03814735	1	BMPR2
CYC-116	1	BMPR2
GSK-461364	1	EIF2AK4
LY-3009120	1	EIF2AK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
EIF2AK4	170	Binding:170
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
EIF2AK4	170

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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, EIF2AK4
RUXOLITINIB	4	BMPR2
BOSUTINIB	4	BMPR2, EIF2AK4
DEUCRAVACITINIB	4	BMPR2
NINTEDANIB	4	BMPR2, EIF2AK4
SUNITINIB	4	BMPR2, EIF2AK4
NERATINIB	4	EIF2AK4
DASATINIB	4	EIF2AK4
ERLOTINIB	4	EIF2AK4
MIDOSTAURIN	4	EIF2AK4
LINIFANIB	3	BMPR2
ORANTINIB	3	BMPR2
DOVITINIB	3	BMPR2, EIF2AK4
LESTAURTINIB	3	BMPR2, EIF2AK4
MOTESANIB	3	EIF2AK4
SILMITASERTIB	2	BMPR2
SU-014813	2	BMPR2, EIF2AK4
OSI-027	2	BMPR2
AT-9283	2	BMPR2
TOZASERTIB	2	BMPR2, EIF2AK4
R-406	2	EIF2AK4
RAF-265	2	EIF2AK4
PELITINIB	2	EIF2AK4
KW-2449	1	BMPR2, EIF2AK4
RGB-286638	1	BMPR2
PF-03814735	1	BMPR2
CYC-116	1	BMPR2
GSK-461364	1	EIF2AK4
LY-3009120	1	EIF2AK4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BMPR2, EIF2AK4
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.