Juvenile polyposis syndrome: genes and variants
Explore variant evidence for Juvenile polyposis syndrome across 2 analyzed proteins (SMAD4, BMPR1A). Linked ClinVar records include 26 pathogenic or likely pathogenic variants, 1,191 variants of uncertain significance and 166 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Juvenile polyposis 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.
18 ClinVar pathogenic / likely pathogenic and 585 uncertain variants in SMAD4 have source records linked to Juvenile polyposis syndrome. Association strength is not clinical gene validity.
BMPR1A: Bone morphogenetic protein receptor type-1A
It transduces BMP signals that regulate epithelial growth, differentiation, and tissue patterning through SMAD proteins and other pathways. Germline loss-of-function variants cause juvenile polyposis syndrome and can substantially increase gastrointestinal cancer risk.
8 ClinVar pathogenic / likely pathogenic and 772 uncertain variants in BMPR1A have source records linked to Juvenile polyposis syndrome. Association strength is not clinical gene validity.
Where Juvenile polyposis syndrome variants cluster
- SMAD4 MH2 (positions 323–552): 18 of 18 ClinVar pathogenic / likely pathogenic variants, 2.4× more than its size predicts.
- BMPR1A Extracellular (positions 24–152): 4 of 8 ClinVar pathogenic / likely pathogenic variants, 2.1× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Juvenile polyposis syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SMAD4 R361C | 361 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 I500V | 500 | MH2 | Pathogenic / likely pathogenic (★★) |
| BMPR1A M1I | 1 | Pathogenic / likely pathogenic (★★) | |
| BMPR1A M1L | 1 | Pathogenic / likely pathogenic (★★) | |
| BMPR1A M1V | 1 | Pathogenic / likely pathogenic (★★) | |
| BMPR1A E411K | 411 | Protein kinase | Pathogenic / likely pathogenic (★★) |
| SMAD4 R361G | 361 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 R361H | 361 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 C363Y | 363 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 C363G | 363 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 I500T | 500 | MH2 | Pathogenic / likely pathogenic (★★) |
| BMPR1A C124S | 124 | Extracellular | Pathogenic / likely pathogenic (★★) |
| BMPR1A C124Y | 124 | Extracellular | Pathogenic / likely pathogenic (★★) |
| SMAD4 D351V | 351 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 G352R | 352 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 Y353C | 353 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 C499R | 499 | MH2 | Pathogenic / likely pathogenic (★★) |
| BMPR1A R119C | 119 | Extracellular | Pathogenic / likely pathogenic (★★) |
| BMPR1A G144R | 144 | Extracellular | Pathogenic / likely pathogenic (★★) |
| SMAD4 R380K | 380 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 W524C | 524 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 R361S | 361 | MH2 | Pathogenic / likely pathogenic (★) |
| SMAD4 I500M | 500 | MH2 | Pathogenic / likely pathogenic (★) |
| SMAD4 L364W | 364 | MH2 | Pathogenic / likely pathogenic (★) |
| SMAD4 I383M | 383 | MH2 | Pathogenic / likely pathogenic (★) |
| SMAD4 L533P | 533 | MH2 | Pathogenic / likely pathogenic (★) |
Which prediction tools work for Juvenile polyposis syndrome
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 89 out of 100
- PolyPhen-2: 80 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Familial thoracic aortic aneurysm and aortic dissection also has ClinVar records linked to SMAD4 variants; they fall in the same places as the Juvenile polyposis syndrome variants (12 pathogenic / likely pathogenic).
Diseases related to Juvenile polyposis syndrome
- Generalized juvenile polyposis/juvenile polyposis coli, also linked to BMPR1A and SMAD4
- Familial thoracic aortic aneurysm and aortic dissection, also linked to SMAD4
- Pulmonary arterial hypertension, also linked to BMPR1A
- Esophageal cancer, 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
- Polyposis syndrome, hereditary mixed, 2, also linked to BMPR1A
- Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, also linked to SMAD4
Frequently asked questions
Which genes have records linked to Juvenile polyposis syndrome?
This view contains 2 analyzed proteins: SMAD4, BMPR1A. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 26 pathogenic or likely pathogenic variants, 1,191 variants of uncertain significance and 166 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 1,454 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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