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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IRX1
iroquois homeobox 1
Chromosome 5 · 5p15.33
NCBI Gene: 79192Ensembl: ENSG00000170549.4HGNC: HGNC:14358UniProt: P78414
34PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific DNA bindingsequence-specific double-stranded DNA bindingDNA-binding transcription repressor activity, RNA polymerase II-specificnegative regulation of transcription by RNA polymerase IIneurodegenerative diseaseRaynaud diseasecoronary artery diseasehypertension
✦AI Summary

IRX1 (Iroquois homeobox 1) is a transcription factor that functions as both a tumor suppressor and developmental regulator with tissue-specific roles. As a transcriptional regulator, IRX1 exhibits DNA-binding activity and can act as both an activator and repressor of target genes 1. In gastric tissue, IRX1 functions as a tumor suppressor, directly regulating genes involved in angiogenesis (BDKRB2), cell proliferation (HIST2H2BE), and invasion (FGF7) 1. IRX1 expression is frequently silenced in gastric cancer through promoter hypermethylation, which can be induced by Helicobacter pylori infection 2. In oral epithelium, IRX1 plays a crucial role in stem cell plasticity and wound healing by activating SOX9 to promote cell proliferation and stimulating EGF signaling for cell migration 3. Paradoxically, IRX1 shows oncogenic properties in certain contexts, being overexpressed in high-grade IDH-mutant astrocytomas where higher expression correlates with poor prognosis 4. IRX1 inactivation is also commonly found in myeloid leukemia associated with Down syndrome, contributing to MYC pathway upregulation 5. Additionally, IRX1 variants are associated with Raynaud's syndrome, where the gene appears to function in microvasculature regulation 6.

Sources cited
1
IRX1 functions as tumor suppressor in gastric cancer and directly regulates BDKRB2, HIST2H2BE, and FGF7 genes
PMID: 20440264
2
IRX1 expression is silenced by promoter hypermethylation induced by H. pylori infection
PMID: 21649733
3
IRX1 regulates stem cell plasticity in oral epithelium by activating SOX9 and EGF signaling
PMID: 39782692
4
IRX1 is overexpressed in high-grade IDH-mutant astrocytomas and correlates with poor prognosis
PMID: 37116364
5
IRX1 inactivation occurs in myeloid leukemia and contributes to MYC pathway upregulation
PMID: 38513239
6
IRX1 variants are associated with Raynaud's syndrome and microvasculature function
PMID: 39142284
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.51Moderate
Raynaud diseaseOpen Targets
0.41Moderate
coronary artery diseaseOpen Targets
0.37Weak
hypertensionOpen Targets
0.37Weak
myocardial infarctionOpen Targets
0.36Weak
sleep apneaOpen Targets
0.36Weak
Abnormality of the skeletal systemOpen Targets
0.35Weak
biliary tract diseaseOpen Targets
0.34Weak
injuryOpen Targets
0.34Weak
androgenetic alopeciaOpen Targets
0.33Weak
corneal neovascularizationOpen Targets
0.33Weak
adolescent idiopathic scoliosisOpen Targets
0.33Weak
peripheral vascular diseaseOpen Targets
0.33Weak
cardiovascular diseaseOpen Targets
0.30Weak
alcohol drinkingOpen Targets
0.30Weak
schizophreniaOpen Targets
0.29Weak
Sleep DisorderOpen Targets
0.28Weak
mathematical abilityOpen Targets
0.28Weak
type 2 diabetes mellitusOpen Targets
0.25Weak
substance-related disorderOpen Targets
0.25Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KCND2Protein interaction84%SMYD1Protein interaction79%IRX2Shared pathway75%HAND2Protein interaction70%IRX6Shared pathway50%IRX3Shared pathway43%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
74%
Heart
14%
Brain
2%
Ovary
0%
Liver
0%
Gene Interaction Network
Click a node to explore
IRX1KCND2SMYD1IRX2HAND2IRX6IRX3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P78414
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.13LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.79 [0.56–1.13]
RankingsWhere IRX1 stands among ~20K protein-coding genes
  • #11,173of 20,598
    Most Researched34
  • #11,620of 17,882
    Most Constrained (LOEUF)1.13
Genes detectedIRX1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms.
PMID: 38513239
Blood · 2024
1.00
2
Clinical significance of Iroquois Homeobox Gene - IRX1 in human glioma.
PMID: 29328446
Mol Med Rep · 2018
0.90
3
Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa.
PMID: 21649733
J Gastroenterol Hepatol · 2011
0.80
4
Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury.
PMID: 39782692
JCI Insight · 2025
0.70
5
Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma.
PMID: 20440264
Oncogene · 2010
0.60