Iroquois homeobox protein 5 (IRX5)

Iroquois homeobox protein 5 (IRX5) is a transcription factor belonging to the Iroquois homeobox gene family, characterized by a homeodomain that binds DNA and regulates gene expression crucial for the development and function of various tissues. IRX5 plays essential roles in pattern formation during embryogenesis, especially in the heart, where it establishes cardiac electrical gradients by regulating expression of potassium and sodium channels. IRX5 is also important for cell cycle regulation and apoptosis in cancer, where its expression is controlled by vitamin D metabolites and influences cancer cell survival. In adipose tissue, IRX5 suppresses mitochondrial thermogenesis, promoting white fat accumulation and contributing to obesity risk associated with FTO allele variants. Loss-of-function mutations in IRX5 cause Hamamy syndrome, a rare developmental disorder with craniofacial, bone, and heart defects. Research supports IRX5 as a promising therapeutic target in some cancers; however, targeting IRX5 presents safety challenges due to its critical roles in development and tissue homeostasis.

Other names

Iroquois-class homeodomain protein IRX-5IRX5IRX2AIRXB2IRX-2aHomeodomain protein IRX-2AHomeodomain protein IRXB2HMMSIroquois homeobox gene 5Iroquois homeobox protein 5Irx5 (mouse orthologue)

Transcriptional repression or activation of target genes, such as potassium channels (Kv4.2/KCND2) and sodium channels (SCN5A) in cardiac tissue. Modulation of cell cycle regulators (p21, p53) in cancer cells. IRX5 knockdown leads to G2-M arrest and increased apoptosis. 1,25-dihydroxyvitamin D3 down-regulates IRX5, promoting cell cycle arrest and apoptosis in cancer.