Hereditary hemorrhagic telangiectasia: genes and variants
Hereditary hemorrhagic telangiectasia is linked to 2 analyzed proteins (ACVRL1 and SMAD4). 4 DNA variants are known to cause it; 1 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Hereditary hemorrhagic telangiectasia
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.
4 disease-causing and 1 uncertain variants in ACVRL1 are linked to Hereditary hemorrhagic telangiectasia.
SMAD4: SMAD family member 4
It forms transcriptional complexes with activated receptor-regulated SMADs and is the central nuclear mediator shared by TGF-beta and BMP pathways. Germline loss-of-function variants cause juvenile polyposis or combined juvenile-polyposis-HHT, while specific gain-of-function variants cause Myhre syndrome.
0 disease-causing and 0 uncertain variants in SMAD4 are linked to Hereditary hemorrhagic telangiectasia.
Weakly linked (only a few uncertain records): RASA1.
Known disease-causing variants in Hereditary hemorrhagic telangiectasia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ACVRL1 L273P | 273 | Protein kinase | Disease-causing (★★) |
| ACVRL1 W50R | 50 | Extracellular | Disease-causing (★★) |
| ACVRL1 R67Q | 67 | Extracellular | Disease-causing (★★) |
| ACVRL1 D330H | 330 | Protein kinase | Disease-causing (★) |
Same protein, different disease
- Telangiectasia, hereditary hemorrhagic, type 2 is also caused by ACVRL1 variants; they fall mostly in different places as the Hereditary hemorrhagic telangiectasia 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 Hereditary hemorrhagic telangiectasia variants (6 disease-causing).
- Pulmonary hypertension, primary, 1 is also caused by ACVRL1 variants; they fall mostly in different places as the Hereditary hemorrhagic telangiectasia variants (3 disease-causing).
Diseases related to Hereditary hemorrhagic telangiectasia
- Familial thoracic aortic aneurysm and aortic dissection, also linked to SMAD4
- Hereditary factor VIII deficiency disease, also linked to ACVRL1
- Telangiectasia, hereditary hemorrhagic, type 2, also linked to ACVRL1
- Pulmonary hypertension, primary, 1, also linked to ACVRL1
- Pulmonary arterial hypertension, also linked to ACVRL1
- Juvenile polyposis syndrome, also linked to SMAD4
- Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia, also linked to ACVRL1
- Familial pancreatic carcinoma, also linked to SMAD4
- Carcinoma of pancreas, also linked to SMAD4
- Generalized juvenile polyposis/juvenile polyposis coli, also linked to SMAD4
- Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, also linked to SMAD4
Frequently asked questions
Which genes are linked to Hereditary hemorrhagic telangiectasia?
In CATVariant, Hereditary hemorrhagic telangiectasia is linked to 2 analyzed proteins: ACVRL1 (Activin receptor type-1-like) and SMAD4 (SMAD family member 4).
How many genetic variants are linked to Hereditary hemorrhagic telangiectasia?
8 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hereditary hemorrhagic telangiectasia look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
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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