SMAD2 (SMAD family member 2) variants and mutations

SMAD2 (also known as SMAD family member 2) is a human protein-coding gene encoding a SMAD family member 2 protein. It carries activated TGF-beta and activin signals from receptors to the nucleus and regulates developmental and extracellular-matrix gene programs. Heterozygous pathogenic variants can cause syndromic thoracic aortic aneurysm and dissection with variable craniofacial and cardiovascular features. This analysis covers 1,791 SMAD2 variants and mutations. Of these, 26% have computational variant effect predictions. Disease context includes Loeys-Dietz syndrome 6, congenital heart defects, multiple types, 8, with or without heterotaxy, and Loeys-Dietz syndrome. Example SMAD2 variants include M1?, S2*, and S2L.

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 SMAD2 variants

Examples include M1?, S2*, S2L, S2P, S2W, S3C, S3F, I4M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.