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Iroquois homeobox 3
Symbols IRX3 ; IRX-1; IRXB1
External IDs OMIM612985 MGI1197522 HomoloGene7385 GeneCards: IRX3 Gene
Species Human Mouse
Entrez 79191 16373
Ensembl ENSG00000177508 ENSMUSG00000031734
UniProt P78415 P81067
RefSeq (mRNA) NM_024336 NM_001253822
RefSeq (protein) NP_077312 NP_001240751
Location (UCSC) Chr 16:
54.28 – 54.29 Mb
Chr 8:
91.8 – 91.8 Mb
PubMed search [1] [2]

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 tranlates a morphogen gradient into transcriptional events, and is directly regulated by NKX2-2.[4]

Clinical significance[edit]

Association with obesity[edit]

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]


  1. ^ a b "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. PMID 25398016. 
  5. ^ Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA (Mar 2014). "Obesity-associated variants within FTO form long-range functional connections with IRX3". Nature 507 (7492): 371–5. doi:10.1038/nature13138. PMID 24646999. 
  6. ^ Claussnitzer M, Dankel S, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J, Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M (Aug 2015). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". New England Journal of Medicine. doi:10.1056/NEJMoa1502214. PMID 26287746. Lay summaryBoston Business Journal (20 Aug 2015). open access publication - free to read

Further reading[edit]

  • Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, Bruinenberg M, Heap GA, Platteel M, Ryan AW, de Kovel C, Holmes GK, Howdle PD, Walters JR, Sanders DS, Mulder CJ, Mearin ML, Verbeek WH, Trimble V, Stevens FM, Kelleher D, Barisani D, Bardella MT, McManus R, van Heel DA, Wijmenga C (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. PMID 19240061. 
  • Ragvin A, Moro E, Fredman D, Navratilova P, Drivenes Ø, Engström PG, Alonso ME, de la Calle Mustienes E, Gómez Skarmeta JL, Tavares MJ, Casares F, Manzanares M, van Heyningen V, Molven A, Njølstad PR, Argenton F, Lenhard B, Becker TS (Jan 2010). "Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3". Proceedings of the National Academy of Sciences of the United States of America 107 (2): 775–80. doi:10.1073/pnas.0911591107. PMC 2818943. PMID 20080751. 

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