Pulmonary hypertension, primary, 1: genes and variants

Genes linked to Pulmonary hypertension, primary, 1

• 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.

  38 disease-causing and 86 uncertain variants in BMPR2 are linked to Pulmonary hypertension, primary, 1.

• ACVRL1: Activin receptor type-1-like

  It mediates BMP9 and BMP10 signaling in vascular endothelial cells and helps maintain normal vessel maturation and quiescence. Heterozygous loss-of-function variants cause hereditary hemorrhagic telangiectasia type 2, with telangiectasias and arteriovenous malformations.

  3 disease-causing and 0 uncertain variants in ACVRL1 are linked to Pulmonary hypertension, primary, 1.

Where Pulmonary hypertension, primary, 1 variants cluster

• BMPR2 Extracellular (positions 27–150): 20 of 38 disease-causing changes, 4.4× more than its size predicts.

Known disease-causing variants in Pulmonary hypertension, primary, 1

Uncertain variants in Pulmonary hypertension, primary, 1 that look disease-causing

Which prediction tools work for Pulmonary hypertension, primary, 1

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• PolyPhen-2: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 90 out of 100

Same protein, different disease

• Pulmonary arterial hypertension is also caused by BMPR2 variants; they fall mostly in different places as the Pulmonary hypertension, primary, 1 variants (29 disease-causing).
• Primary pulmonary hypertension is also caused by BMPR2 variants; they fall in the same places as the Pulmonary hypertension, primary, 1 variants (13 disease-causing).
• Telangiectasia, hereditary hemorrhagic, type 2 is also caused by ACVRL1 variants; they fall mostly in different places as the Pulmonary hypertension, primary, 1 variants (178 disease-causing).
• Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia is also caused by ACVRL1 variants; they fall mostly in different places as the Pulmonary hypertension, primary, 1 variants (6 disease-causing).
• Hereditary hemorrhagic telangiectasia is also caused by ACVRL1 variants; they fall mostly in different places as the Pulmonary hypertension, primary, 1 variants (4 disease-causing).

Diseases related to Pulmonary hypertension, primary, 1

• Pulmonary arterial hypertension, also linked to ACVRL1 and BMPR2
• Hereditary factor VIII deficiency disease, also linked to ACVRL1
• Telangiectasia, hereditary hemorrhagic, type 2, also linked to ACVRL1
• Primary pulmonary hypertension, also linked to BMPR2
• Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia, also linked to ACVRL1
• Hereditary hemorrhagic telangiectasia, also linked to ACVRL1
• Pulmonary arterial hypertension associated with congenital heart disease, also linked to BMPR2

Frequently asked questions

Which genes are linked to Pulmonary hypertension, primary, 1?

In CATVariant, Pulmonary hypertension, primary, 1 is linked to 2 analyzed proteins: BMPR2 (Bone morphogenetic protein receptor type-2) and ACVRL1 (Activin receptor type-1-like).

How many genetic variants are linked to Pulmonary hypertension, primary, 1?

199 variants: 41 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 86 are of uncertain significance or have conflicting reports.

Which uncertain variants in Pulmonary hypertension, primary, 1 look disease-causing?

1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example BMPR2 C60F. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Pulmonary hypertension, primary, 1?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.90, based on 41 disease-causing and 62 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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