Tbx20, a member of the Tbx1 subfamily of T-box-containing genes, plays fundamental roles in cardiovascular development, homeostasis, and cardiac remodeling in response to pathophysiological stresses. It is involved in pathways related to chamber septation, growth, valvulogenesis, and transcriptional networks during cardiac development [1].

Mutations in TBX20 are associated with congenital heart defects (CHDs), dilated cardiomyopathy, heart arrhythmia, and left ventricular non-compaction cardiomyopathy. In colorectal cancer, TBX20 acts as a tumor suppressor by impairing NHEJ-mediated DNA repair [1,2,5]. Disrupting the Tbx20-TLE interaction in a mouse model impaired cardiac morphogenic events like looping and chamber formation, highlighting its role in heart development [3]. Adding TBX20 to a reprogramming cocktail improved contractility and mitochondrial function during direct human cardiac reprogramming [4]. TBX20 also regulates angiogenesis through the PROK2-PROKR1 pathway [6].

In conclusion, Tbx20 is crucial for normal cardiac development, function, and angiogenesis. Mouse models, especially those with disrupted Tbx20-TLE interaction, have been valuable in revealing its role in cardiac morphogenesis. The gene's association with various heart diseases and its tumor-suppressive role in colorectal cancer emphasize its significance in understanding disease mechanisms and potential therapeutic strategies.