Gene SMAD3
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Also known as
MADH3, JV15-2, HsT17436, LDS3, MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 3Overview
SMAD3 (SMAD Family Member 3) is a crucial intracellular signal transducer and transcriptional regulator in the transforming growth factor-beta (TGF-beta) signaling pathway. When TGF-beta ligands bind to their receptors on the cell surface, SMAD3 becomes phosphorylated and forms complexes with SMAD4, which then translocate to the nucleus to regulate gene transcription. This pathway is essential for numerous biological processes including cell growth, differentiation, apoptosis, immune regulation, and extracellular matrix production. SMAD3 plays particularly important roles in cardiovascular development, wound healing, fibrosis, and immune system function.Mutations in SMAD3 cause Loeys-Dietz syndrome type 3 (LDS3), an autosomal dominant connective tissue disorder characterized by aortic aneurysms and dissections, arterial tortuosity, skeletal abnormalities, and craniofacial features. Affected individuals have an increased risk of life-threatening cardiovascular complications at a young age, requiring careful monitoring and often prophylactic surgical intervention. Beyond LDS3, SMAD3 variants have been associated with susceptibility to coronary artery disease and osteoarthritis. The gene also plays a significant role in cancer biology, where aberrant TGF-beta/SMAD3 signaling can promote tumor progression, metastasis, and immune evasion in various malignancies.