Hmx3, also known as Nkx5.1, is a homeodomain-containing protein. It has essential roles in CNS and ear development [3,4,5,6,7,8]. Hmx3 is involved in apoptosis and KRAS signaling pathways in colorectal cancer [1]. In acute myelomonocytic leukemia, it drives cancer-associated E2F and MYC gene programs [2].

In mouse models, targeted disruption of the Hmx3 gene leads to abnormal circling behavior and severe vestibular defects due to a depletion of sensory cells in the saccule and utricle, and a complete loss of the horizontal semicircular canal crista, as well as a fusion of the utricle and saccule endolymphatic spaces [5]. In addition, most Hmx3 null females have a reproductive defect as embryos fail to implant successfully in the Hmx3 null uterus [5]. Knockdown of Hmx3 in KMT2A::MLLT3 patient cells results in cell cycle arrest, monocytic differentiation and apoptosis [2]. In CRC cells, knockdown of Hmx3 enhances cell proliferation, migration, and invasion [1].

In conclusion, Hmx3 is crucial for inner ear and CNS development, as well as pregnancy in mice. In diseases, it plays significant roles in colorectal cancer and acute myelomonocytic leukemia. The study of Hmx3 knockout mouse models has provided valuable insights into its functions in these biological processes and disease conditions.