SMAD6
Chr 15ADSMAD family member 6
Also known as: AOVD2, HsT17432, MADH6, MADH7
SMAD6 encodes an inhibitory SMAD protein that negatively regulates BMP and TGF-beta signaling pathways, which are critical for bone, cartilage, and cardiovascular development. Mutations cause autosomal dominant craniosynostosis, radioulnar synostosis, and aortic valve disease. The gene is not highly constrained against loss-of-function variants, consistent with its role in developmental disorders affecting specific tissue types rather than causing severe multisystem disease.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SMAD6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools