IRX3

IRX3
Identifiers
Aliases	IRX3, IRX-1, IRXB1, iroquois homeobox 3
External IDs	OMIM: 612985 MGI: 1197522 HomoloGene: 7385 GeneCards: IRX3
Gene location (Human)
Chr.	Chromosome 16 (human)[1]
End	54,286,787 bp[1]
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)[2]
End	91,802,067 bp[2]
Gene ontology
Molecular function	• sequence-specific DNA binding; • DNA binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	• cytoplasm; • axon; • cell nucleus;
Biological process	• multicellular organism development; • mesoderm development; • specification of loop of Henle identity; • metanephros development; • regulation of transcription, DNA-templated; • negative regulation of neuron differentiation; • positive regulation of neuron differentiation; • transcription, DNA-templated; • proximal/distal pattern formation involved in nephron development; • regulation of transcription from RNA polymerase II promoter; • energy homeostasis;
	Sources:Amigo / QuickGO
Orthologs
	79191
	16373
	ENSG00000177508
	ENSMUSG00000031734
	P78415
	P81067
	NM_024336
	NM_001253822; NM_008393
	NP_077312
	NP_001240751; NP_032419
	Wikidata
View/Edit Human	View/Edit Mouse

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.[5]

Function

IRX3 is a member of the Iroquois homeobox gene family and plays a role in an early step of neural development.[6] Members of this family appear to play multiple roles during pattern formation of vertebrate embryos.[5][7] 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.[8]

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.[9] Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures.[10] Genetic variants of FTO and IRX3 genes are in high linkage disequilibrium and are associated with obesity risk.[11]

References

GRCh38: Ensembl release 89: ENSG00000177508 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000031734 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: iroquois homeobox 3".
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.
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. S2CID 37046813.
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. Bibcode:2014PLoSO...9k1430L. doi:10.1371/journal.pone.0111430. PMC 4232242. PMID 25398016.
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. Bibcode:2014Natur.507..371S. doi:10.1038/nature13138. PMC 4113484. PMID 24646999.
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 (10): 895–907. doi:10.1056/NEJMoa1502214. PMC 4959911. PMID 26287746. Lay summary – Boston Business Journal (20 Aug 2015).
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. 43 (5): 1–6. doi:10.3109/03014460.2015.1103902. PMID 26440677. S2CID 19868664.

IRX3

Function

Clinical significance

Association with obesity

References

Further reading