IRF6 Gene - Interferon Regulatory Factor 6
Key regulator of craniofacial development and epithelial differentiation
Gene Information Card
| Symbol | IRF6 |
|---|---|
| Full Name | Interferon Regulatory Factor 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q32.2 |
| NCBI Gene ID | 3664 ncbi.nlm.nih.gov/gene/3664 |
| Ensembl ID | ENSG00000117595 |
| UniProt ID | O14896 |
| OMIM ID | 607199 |
| HGNC ID | 6121 |
| Aliases | VWS1, PPS, OFC6, IRF-6 |
Description
IRF6 encodes interferon regulatory factor 6, a member of the IRF family of transcription factors. It plays a critical role in craniofacial development, particularly in the formation of the palate, lip, and other epithelial structures. Mutations in IRF6 are the primary cause of Van der Woude syndrome and popliteal pterygium syndrome, and are also associated with isolated cleft lip and palate.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Van der Woude syndrome | Loss-of-function mutations in IRF6 disrupt epithelial-mesenchymal signaling during palatogenesis | OMIM #119300; ClinVar |
| Popliteal pterygium syndrome | Dominant-negative or missense mutations impair IRF6 DNA-binding and transcriptional activity | OMIM #119500; ClinVar |
| Isolated cleft lip/palate | Common variants (e.g., rs642961) in IRF6 regulatory regions increase risk | GWAS; PMID 19494218 |
| Orofacial cleft 6 | IRF6 mutations cause syndromic and non-syndromic forms | OMIM #608864 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 17.2 | Medium |
| Oral mucosa | 15.8 | Medium |
| Esophagus | 12.4 | Medium |
| Placenta | 8.9 | Low |
| Lung | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 22.1 | High expression in epithelial cells |
| A431 (epidermoid carcinoma) | 18.5 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 3.2 | Low expression |
| K562 (leukemia) | 1.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.250G>A (p.Gly84Arg) | Missense | Common in VWS | Disrupts DNA-binding domain; loss of function |
| c.445C>T (p.Arg149Cys) | Missense | Common in PPS | Dominant-negative effect |
| c.1234delC (p.Leu412Trpfs*28) | Frameshift | Rare | Premature truncation; loss of function |
| rs642961 (G>A) | Regulatory variant | Population frequency ~0.15 | Alters IRF6 enhancer; increases cleft lip risk |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that reduce IRF6 protein levels or disrupt DNA binding; cause Van der Woude syndrome.
Gain of Function (GOF)
Not well documented; most pathogenic IRF6 mutations are loss-of-function or dominant-negative.
Dominant Negative (DN)
Missense mutations in the DNA-binding domain (e.g., p.Arg149Cys) that interfere with wild-type IRF6 function; cause popliteal pterygium syndrome.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IRF6 in epithelial development and differentiation
• TGF-beta signaling pathway (indirect regulation via IRF6)
• p63-IRF6 regulatory network in craniofacial development
Protein Summary
IRF6 is a 467-amino acid transcription factor containing a conserved N-terminal DNA-binding domain and a C-terminal IRF association domain. It forms homodimers or heterodimers with other IRF family members and regulates genes involved in cell proliferation, differentiation, and apoptosis during epithelial and craniofacial development. The protein is essential for proper palate and lip fusion, and its dysfunction leads to syndromic clefting disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRF6 Knockout HEK293 Cell Line | EDJ-KQ50398 | Human | 3664 | Details Get a Quote |
| IRF6 Knockout HeLa Cell Line | EDJ-KQ53672 | Human | 3664 | Details Get a Quote |
| IRF6 Knockout A-549 Cell Line | EDJ-KQ62146 | Human | 3664 | Details Get a Quote |
| IRF6 Knockout HCT 116 Cell Line | EDJ-KQ70636 | Human | 3664 | Details Get a Quote |
