Gene TGFBR1
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Also known as
TGF-beta Receptor Type-1, ALK5, ACVRLK4, LDS1, LDS2A, TGFR-1Overview
TGFBR1 (Transforming Growth Factor Beta Receptor 1) encodes a type I serine/threonine kinase receptor that mediates cellular responses to TGF-beta family ligands. Upon TGF-beta binding to the type II receptor (TGFBR2), TGFBR1 is recruited and phosphorylated, becoming activated to phosphorylate SMAD2 and SMAD3 proteins. This initiates downstream signaling cascades that regulate gene transcription affecting cell proliferation, differentiation, apoptosis, immune function, and extracellular matrix production. TGFBR1 is essential for normal development, particularly of the cardiovascular and skeletal systems, and plays complex roles in cancer where it can act as both a tumor suppressor and promoter depending on context.Mutations in TGFBR1 cause Loeys-Dietz syndrome types 1 and 2, autosomal dominant connective tissue disorders characterized by arterial aneurysms and tortuosity, hypertelorism, bifid uvula or cleft palate, and skeletal abnormalities. These mutations typically result in haploinsufficiency or dominant-negative effects that disrupt TGF-beta signaling. Affected individuals have significantly increased risk of aortic dissection and require regular cardiovascular surveillance and often prophylactic surgery. Beyond LDS, TGFBR1 variants have been associated with hereditary hemorrhagic telangiectasia, familial thoracic aortic aneurysm, and cancer susceptibility. Understanding TGFBR1 genetics is crucial for identifying individuals at risk for life-threatening cardiovascular complications and implementing appropriate monitoring and intervention strategies.