HAND2 A gene on chromosome 4q33 that encodes a DNA-binding basic helix-loop-helix (bHLH) transcription factor which plays an essential role in cardiac morphogenesis: it works in complement with HAND1 in the formation of the right ventricle and of the aortic arch arteries. HAND2 is required for vascular development and regulation of angiogenesis, possibly by a VEGF signalling pathway; it also plays a key role in limb development, particularly in the establishment of anterior-posterior polarisation, acting as an upstream regulator of sonic hedgehog (Shh) induction in the limb bud. It is involved in the development of branchial arches and head and neck structures. HAND2 dimerises with TCF3 gene products E12 and E47 and hairy-related transcription factors (HAND2, HEY1, HEY2 and HEYL), and it interacts with MDFIC. It is expressed in the heart.