Primary pulmonary hypertension: genes and variants
Primary pulmonary hypertension is linked to 1 analyzed protein (BMPR2). 13 DNA variants are known to cause it; 81 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Primary pulmonary hypertension
BMPR2: Bone morphogenetic protein receptor type-2
It initiates BMP signaling in vascular cells and helps maintain normal pulmonary-artery structure and endothelial function. Heterozygous loss-of-function variants are the most common known genetic cause of heritable pulmonary arterial hypertension.
13 disease-causing and 81 uncertain variants in BMPR2 are linked to Primary pulmonary hypertension.
Where Primary pulmonary hypertension variants cluster
- BMPR2 Extracellular (positions 27–150): 5 of 13 disease-causing changes, 3.2× more than its size predicts.
- BMPR2 Protein kinase (positions 203–504): 8 of 13 disease-causing changes, 2.1× more than its size predicts.
Known disease-causing variants in Primary pulmonary hypertension
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| BMPR2 C117Y | 117 | Extracellular | Disease-causing (★★) |
| BMPR2 R491W | 491 | Protein kinase | Disease-causing (★★) |
| BMPR2 C496Y | 496 | Protein kinase | Disease-causing (★★) |
| BMPR2 Y67C | 67 | Extracellular | Disease-causing (★★) |
| BMPR2 N126S | 126 | Extracellular | Disease-causing (★★) |
| BMPR2 R491L | 491 | Protein kinase | Disease-causing (★) |
| BMPR2 C117S | 117 | Extracellular | Disease-causing (★) |
| BMPR2 D487E | 487 | Protein kinase | Disease-causing (★) |
| BMPR2 A490V | 490 | Protein kinase | Disease-causing (★) |
| BMPR2 C496W | 496 | Protein kinase | Disease-causing (★) |
| BMPR2 C99Y | 99 | Extracellular | Disease-causing (★) |
| BMPR2 C347R | 347 | Protein kinase | Disease-causing (★) |
| BMPR2 M449R | 449 | Protein kinase | Disease-causing (★) |
Uncertain variants in Primary pulmonary hypertension that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| BMPR2 C99R | 99 | Extracellular | Conflicting reports (★) | +7: C99Y at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.942 |
Which prediction tools work for Primary pulmonary hypertension
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 93 out of 100
Same protein, different disease
- Pulmonary hypertension, primary, 1 is also caused by BMPR2 variants; they fall mostly in different places as the Primary pulmonary hypertension variants (38 disease-causing).
- Pulmonary arterial hypertension is also caused by BMPR2 variants; they fall mostly in different places as the Primary pulmonary hypertension variants (29 disease-causing).
Diseases related to Primary pulmonary hypertension
- Pulmonary hypertension, primary, 1, also linked to BMPR2
- Pulmonary arterial hypertension, also linked to BMPR2
- Pulmonary arterial hypertension associated with congenital heart disease, also linked to BMPR2
Frequently asked questions
Which genes are linked to Primary pulmonary hypertension?
In CATVariant, Primary pulmonary hypertension is linked to 1 analyzed protein: BMPR2 (Bone morphogenetic protein receptor type-2).
How many genetic variants are linked to Primary pulmonary hypertension?
128 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 81 are of uncertain significance or have conflicting reports.
Which uncertain variants in Primary pulmonary hypertension look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example BMPR2 C99R. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Primary pulmonary hypertension?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 13 disease-causing and 50 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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