IRX3 Gene - Iroquois Homeobox 3
Key regulator of adipogenesis, obesity, and neural development
Gene Information Card
| Symbol | IRX3 |
|---|---|
| Full Name | Iroquois homeobox 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q12.2 |
| NCBI Gene ID | 79191 ncbi.nlm.nih.gov/gene/79191 |
| Ensembl ID | ENSG00000103056 |
| UniProt ID | P78415 |
| OMIM ID | 612985 |
| HGNC ID | 14360 |
| Aliases | IRX-3, Iroquois-class homeodomain protein IRX-3 |
Description
IRX3 encodes a member of the Iroquois homeobox gene family, which are transcription factors involved in pattern formation and regional specification during embryonic development. IRX3 is widely expressed in the developing nervous system, heart, and limbs. In adults, it is highly expressed in adipose tissue and the brain. Genome-wide association studies have linked non-coding variants in the FTO gene to obesity, and functional studies show that these variants regulate IRX3 expression, implicating IRX3 as a key mediator of obesity risk. IRX3 also plays roles in cardiac conduction and neural crest cell migration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Non-coding variants in FTO intron 1 regulate IRX3 expression in adipose tissue and hypothalamus, affecting energy balance and adipogenesis. | GWAS, functional studies (Claussnitzer et al., 2015, Nature) |
| Type 2 diabetes | Obesity-mediated IRX3 dysregulation contributes to insulin resistance and metabolic dysfunction. | GWAS, expression QTL studies |
| Congenital heart disease | IRX3 is required for proper cardiac conduction system development; mutations may disrupt heart patterning. | Animal models, expression studies |
| Neural tube defects | IRX3 is expressed in the developing neural tube; altered expression may contribute to closure defects. | Expression studies in mouse embryos |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 45.2 | High |
| Brain (cerebellum) | 38.7 | High |
| Heart | 22.1 | Medium |
| Lung | 8.4 | Low |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Adipocytes (differentiated) | 62.5 | High expression in mature adipocytes |
| SH-SY5Y (neuroblastoma) | 28.3 | Moderate expression |
| HeLa (cervical carcinoma) | 12.1 | Low expression |
| HepG2 (hepatocellular carcinoma) | 4.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1421085 (T>C) | SNV (intronic, FTO locus) | ~40% in Europeans | Disrupts ARID5B repressor binding, increases IRX3 expression in adipocytes, leading to reduced mitochondrial thermogenesis and increased lipid storage |
| rs9939609 (T>A) | SNV (intronic, FTO locus) | ~45% in Europeans | Associated with increased IRX3 expression and higher BMI |
| rs8050136 (C>A) | SNV (intronic, FTO locus) | ~42% in Europeans | Linked to IRX3 expression changes and obesity risk |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in humans; mouse knockout models show reduced body weight and altered adiposity.
Gain of Function (GOF)
Increased IRX3 expression due to FTO intronic variants (e.g., rs1421085) is associated with obesity, suggesting a gain-of-function effect in adipocytes.
Dominant Negative (DN)
Not reported for IRX3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Adipogenesis pathway
• Wnt signaling pathway
• Notch signaling pathway
• Cardiac conduction system development
Protein Summary
IRX3 is a 480-amino acid homeodomain transcription factor containing a conserved Iroquois-class homeobox DNA-binding domain. It localizes to the nucleus and regulates target genes involved in cell fate determination, regional patterning, and metabolism. The protein interacts with other transcription factors and co-regulators to modulate gene expression in a tissue-specific manner. Structural studies indicate that the homeodomain recognizes specific DNA sequences (e.g., TAAT motifs) to control transcriptional programs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRX3 Knockout HEK293 Cell Line | EDJ-KQ13865 | Human | 79191 | Details Get a Quote |
| IRX3 Knockout HeLa Cell Line | EDJ-KQ43708 | Human | 79191 | Details Get a Quote |
| IRX3 Knockout A-549 Cell Line | EDJ-KQ65669 | Human | 79191 | Details Get a Quote |
| IRX3 Knockout HCT 116 Cell Line | EDJ-KQ74093 | Human | 79191 | Details Get a Quote |
