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RefSeq (mRNA)



RefSeq (protein)



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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.[1]


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]


  1. 1.0 1.1 "Entrez Gene: iroquois homeobox 3".
  2. Bellefroid EJ, Kobbe A, Gruss P, Pieler T, Gurdon JB, Papalopulu N (Jan 1998). "Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification". The EMBO Journal. 17 (1): 191–203. doi:10.1093/emboj/17.1.191. PMC 1170370. PMID 9427753.
  3. 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. PMID 10370142.
  4. Lovrics A, Gao Y, Juhász B, Bock I, Byrne HM, Dinnyés A, Kovács KA (November 2014). "Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord". PLOS ONE. 9 (11): e111430. doi:10.1371/journal.pone.0111430. PMC 4232242. PMID 25398016.
  5. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, et al. (Mar 2014). "Obesity-associated variants within FTO form long-range functional connections with IRX3". Nature. 507 (7492): 371–5. doi:10.1038/nature13138. PMC 4113484. PMID 24646999.
  6. Claussnitzer M, Dankel S, Kim KH, Quon G, Meuleman W, Haugen C, et al. (Aug 2015). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". New England Journal of Medicine. 373: 895–907. doi:10.1056/NEJMoa1502214. PMC 4959911. PMID 26287746. Lay summaryBoston Business Journal (20 Aug 2015).open access publication – free to read
  7. 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. PMID 26440677.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.