IRX3 is a member of the Iroquois homeobox gene family and plays a role in an early step of neural development.[2] Members of this family appear to play multiple roles during pattern formation of vertebrate embryos.[1][3]
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.[4]
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.[5] Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures.[6]
Genetic variants of FTO and IRX3 genes are in high linkage disequilibrium and are associated with obesity risk.[7]
↑Lewis MT, Ross S, Strickland PA, Snyder CJ, Daniel CW (Jun 1999). "Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene, in the human breast". Cell and Tissue Research. 296 (3): 549–54. doi:10.1007/s004410051316. PMID10370142.
↑Srivastava A, Mittal B, Prakash J, Srivastava P, Srivastava N, Srivastava N (2015). "Association of FTO and IRX3 genetic variants to obesity risk in north India". Annals of Human Biology: 1–6. doi:10.3109/03014460.2015.1103902. PMID26440677.
Further reading
Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, et al. (Aug 2009). "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut. 58 (8): 1078–83. doi:10.1136/gut.2008.169052. PMID19240061.
