IRX3

IRX3
Identifiers
Aliases	IRX3, IRX-1, IRXB1, iroquois homeobox 3
External IDs	OMIM: 612985; MGI: 1197522; HomoloGene: 7385; GeneCards: IRX3; OMA:IRX3 - orthologs
Gene location (Human)
Chr.	Chromosome 16 (human)
End	54,286,787 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	92,528,695 bp
RNA expression pattern
	Top expressed in
	nipple; ; human penis; ; skin of arm; ; myocardium of left ventricle; ; bronchial epithelial cell; ; vulva; ; epithelium of lactiferous gland; ; lactiferous duct; ; trachea; ; gingival epithelium;
	Top expressed in
	lacrimal gland; ; left lung lobe; ; maxillary prominence; ; calvaria; ; abdominal wall; ; vestibular membrane of cochlear duct; ; lactiferous gland; ; right lung; ; right lung lobe; ; right ventricle;
	More reference expression data
	n/a
Gene ontology
Molecular function	sequence-specific DNA binding; DNA binding; DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	cytoplasm; axon; 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 by RNA polymerase II; 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]

Discovery and name

The Iroquois family of genes was discovered in Drosophila during a mutagenesis experiment designed to identify genes that affected the development of external sensory organs. When genes of this family were knocked out, the Drosophila flies expressed a unique patterning of bristles reminiscent of Iroquois American Indians, they were subsequently named after them.^[6] The molecular characteristics of these genes allowed the identification of homologs in C. elegans and several other vertebrates.^[7]

Function

IRX3 is a member of the Iroquois homeobox gene family and plays a role in an early step of neural development.^[8] Members of this family appear to play multiple roles during pattern formation of vertebrate embryos.^[5]^[9] 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.^[10] The Irx3 gene controls the subdivision of the neural territory by working together with various other homeodomain factors, all of these factors are expressed in partially overlapping domains along the dorsoventral axis in response to Sonic hedgehog molecules emanating from the floor plate. The combination of these signals defines five regions, each of which will give rise to five types of neurons (V0, V1, V2, MN, and V3). For example, the region that generates V2 neurons expresses both Irx3 and Nkx6.1, while that which forms MN neurons expresses Nkx6.1 alone. Irx3 overexpression in the MN domain transforms MN into V2 neurons.^[11]

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.^[12] Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures.^[13] Genetic variants of FTO and IRX3 genes are in high linkage disequilibrium and are associated with obesity risk.^[14]