IRX3

Iroquois-class homeodomain protein IRX-3, also known as Iroquois homeobox protein 3, is a protein that in humans is encoded by the IRX3 gene.

Function

IRX3 is a member of the Iroquois homeobox gene family and plays a role in an early step of neural development. Members of this family appear to play multiple roles during pattern formation of vertebrate embryos. Specifically, IRX3 contributes to pattern formation in the spinal cord where it translates a morphogen gradient into transcriptional events, and is directly regulated by NKX2-2.

Clinical significance

Association with obesity

Obesity-associated noncoding sequences within FTO interact with the promoter of IRX3 and FTO in human, mouse, and zebrafish. Obesity-associated single nucleotide polymorphisms are related to the expression of IRX3 (not FTO) in the human brain. A direct connection between the expression of IRX3 and body mass and composition was shown through the decrease in body weight of 25-30% in IRX3-deficient mice. This suggests that IRX3 influences obesity. Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures. Genetic variants of FTO and IRX3 genes are in high linkage disequilibrium and are associated with obesity risk.