TAB2 c.1398dup variant leads to haploinsufficiency and impairs extracellular matrix homeostasis.
Transforming growth factor ?-activated kinase 1 (TAK1) mediates multiple biological processes through the nuclear factor ?-light-chain-enhancer of activated B cells (NF-?B) and the mitogen-activated protein kinase (MAPK) signaling pathways. TAK1 activation is tightly regulated by its binding partners (TABs). In particular, binding with TAB2 is crucial for cardiovascular development and extracellular matrix (ECM) homeostasis. In our previous work, we reported a novel multisystem disorder associated with the heterozygous TAB2 c.1398dup variant.