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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IRX6
iroquois homeobox 6
Chromosome 16 · 16q12.2
NCBI Gene: 79190Ensembl: ENSG00000159387.9HGNC: HGNC:14675UniProt: P78412
12PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingDNA-binding transcription factor activity, RNA polymerase II-specificRNA polymerase II cis-regulatory region sequence-specific DNA bindingcell developmentalcohol drinkingchromosome 16q12 duplication syndrometype 2 diabetes mellitusdiabetes mellitus
✦AI Summary

IRX6 is a transcription factor belonging to the Iroquois homeobox gene family that plays critical roles in neuronal development and differentiation 1. As a transcription factor, IRX6 binds to DNA and regulates gene expression, functioning as both an activator and repressor depending on context. In retinal development, IRX6 is specifically required for the terminal differentiation of bipolar interneuron subtypes, particularly type 2 and type 3a OFF bipolar cells 2. IRX6 directly regulates expression of cell type-specific markers including neurokinin 3 receptor (Nk3r) and Vsx1, and prevents aberrant adoption of molecular features between bipolar cell subtypes 2. In spinal cord development, IRX6 expression is confined to ventral domains and serves as a molecular marker for specific motor neuron groups, with HOX proteins directly controlling IRX6 expression 1. Clinically, IRX6 genetic variations are associated with congenital malformations including hypospadias, where polymorphisms in IRX6 increase disease susceptibility 34. Additionally, duplications affecting the IRXB gene cluster containing IRX6 cause autosomal dominant cone dystrophy with characteristic tritanopic color vision defects 5. IRX6 has also been implicated in rare epileptic encephalopathies like Landau-Kleffner syndrome 6.

Sources cited
1
IRX6 is expressed in ventral spinal cord domains and serves as molecular marker for motor neurons, regulated by HOX proteins
PMID: 38853975
2
IRX6 is required for terminal differentiation of type 2 and 3a bipolar cells and directly regulates cell type-specific markers
PMID: 23172916
3
IRX6 polymorphisms are associated with hypospadias susceptibility in Japanese population
PMID: 30063927
4
IRX6 rs6499755 polymorphism increases hypospadias risk in Chinese Northern Han population
PMID: 40547448
5
IRXB cluster duplications affecting IRX6 cause autosomal dominant cone dystrophy with tritanopic color vision defects
PMID: 33891002
6
IRX6 variants identified in patients with Landau-Kleffner syndrome epileptic encephalopathy
PMID: 40944498
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.42Moderate
chromosome 16q12 duplication syndromeOpen Targets
0.33Weak
type 2 diabetes mellitusOpen Targets
0.32Weak
diabetes mellitusOpen Targets
0.32Weak
cutaneous melanomaOpen Targets
0.31Weak
smoking initiationOpen Targets
0.30Weak
response to xenobiotic stimulusOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.22Weak
placenta praeviaOpen Targets
0.20Weak
temporomandibular joint disorderOpen Targets
0.18Weak
post term pregnancyOpen Targets
0.18Weak
hypospadiasOpen Targets
0.08Suggestive
Griscelli diseaseOpen Targets
0.06Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
otosclerosisOpen Targets
0.05Suggestive
Griscelli disease type 3Open Targets
0.05Suggestive
Griscelli syndrome type 3Open Targets
0.05Suggestive
oculocutaneous albinism type 3Open Targets
0.05Suggestive
Griscelli disease type 1Open Targets
0.05Suggestive
Griscelli syndrome type 1Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FTOProtein interaction78%NKX2-2Protein interaction75%SIX3Protein interaction72%OLIG2Protein interaction70%IRX4Shared pathway67%IRX2Shared pathway67%
Tissue Expression6 tissues
Heart
100%
Lung
9%
Ovary
1%
Brain
0%
Bone Marrow
0%
Liver
0%
Gene Interaction Network
Click a node to explore
IRX6FTONKX2-2SIX3OLIG2IRX4IRX2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P78412
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.23LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.96 [0.75–1.23]
RankingsWhere IRX6 stands among ~20K protein-coding genes
  • #16,477of 20,598
    Most Researched12
  • #12,940of 17,882
    Most Constrained (LOEUF)1.23
Genes detectedIRX6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The
PMID: 38853975
bioRxiv · 2024
1.00
2
Single Nucleotide Polymorphisms of HAAO and IRX6 Genes as Risk Factors for Hypospadias.
PMID: 30063927
J Urol · 2019
0.90
3
The Role of IRX Homeobox Genes in Hematopoietic Progenitors and Leukemia.
PMID: 36833225
Genes (Basel) · 2023
0.80
4
Association of
PMID: 40547448
Genet Res (Camb) · 2025
0.70
5
Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene Irx6.
PMID: 23172916
Development · 2012
0.60