Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome: genes and variants
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is linked to 1 analyzed protein (SMAD4). 2 DNA variants are known to cause it; 47 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 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
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.
2 disease-causing and 47 uncertain variants in SMAD4 are linked to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome.
Known disease-causing variants in Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SMAD4 R361G | 361 | MH2 | Disease-causing (★★) |
| SMAD4 G386D | 386 | MH2 | Disease-causing |
Same protein, different disease
- Juvenile polyposis syndrome is also caused by SMAD4 variants; they fall mostly in different places as the Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome variants (18 disease-causing).
- Familial thoracic aortic aneurysm and aortic dissection is also caused by SMAD4 variants; they fall mostly in different places as the Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome variants (12 disease-causing).
Diseases related to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
- Familial thoracic aortic aneurysm and aortic dissection, also linked to SMAD4
- Juvenile polyposis syndrome, also linked to SMAD4
- Familial pancreatic carcinoma, also linked to SMAD4
- Hereditary hemorrhagic telangiectasia, also linked to SMAD4
- Carcinoma of pancreas, also linked to SMAD4
- Generalized juvenile polyposis/juvenile polyposis coli, also linked to SMAD4
Frequently asked questions
Which genes are linked to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome?
In CATVariant, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is linked to 1 analyzed protein: SMAD4 (SMAD family member 4).
How many genetic variants are linked to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome?
60 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 47 are of uncertain significance or have conflicting reports.
Which uncertain variants in Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 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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