SMAD3 (SMAD family member 3) variants and mutations

SMAD3 (also known as SMAD family member 3) is a human protein-coding gene encoding a SMAD family member 3 protein. It carries TGF-beta receptor signals into the nucleus to control extracellular-matrix, differentiation, and growth programs. Heterozygous loss-of-function variants cause Loeys-Dietz syndrome type 3 with arterial aneurysm and dissection risk and often early osteoarthritis. This analysis covers 901 SMAD3 variants and mutations. Of these, 65% have computational variant effect predictions. Disease context includes aneurysm-osteoarthritis syndrome, Aneurysm - osteoarthritis syndrome, and familial thoracic aortic aneurysm and aortic dissection. Example SMAD3 variants include M1I, M1L, and M1T.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SMAD3 variants

Examples include M1I, M1L, M1T, M1V, S2*, S2W, S2P, S2L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.