IRF6

Interferon regulatory factor 6
Identifiers
Symbols	IRF6 ; LPS; OFC6; PIT; PPS; PPS1; VWS; VWS1
External IDs	OMIM: 607199 MGI: 1859211 HomoloGene: 4479 GeneCards: IRF6 Gene
Gene ontology Molecular function • regulatory region DNA binding • DNA binding • transcription factor activity, sequence-specific DNA binding • protein binding Cellular component • nucleus • cytoplasm • cytosol • extracellular exosome Biological process • transcription, DNA-templated • cell cycle arrest • negative regulation of cell proliferation • cytokine-mediated signaling pathway • keratinocyte differentiation • keratinocyte proliferation • positive regulation of transcription, DNA-templated • cell development • interferon-gamma-mediated signaling pathway • type I interferon signaling pathway • mammary gland epithelial cell differentiation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3664	54139
Ensembl	ENSG00000117595	ENSMUSG00000026638
UniProt	O14896	P97431
RefSeq (mRNA)	NM_001206696	NM_016851
RefSeq (protein)	NP_001193625	NP_058547
Location (UCSC)	Chr 1: 209.79 – 209.81 Mb	Chr 1: 193.15 – 193.17 Mb
PubMed search	[1]	[2]

Interferon regulatory factor 6 also known as IRF6 is a protein that in humans is encoded by the IRF6 gene.

Function

This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain.

The function of IRF6 is related to the formation of connective tissue, for example that of the palate. This gene encodes a member of the interferon regulatory transcription factor (IRF) family.

Pathology

A mutation of the IRF6 gene can lead to the autosomal dominant van der Woude syndrome (VWS) or the related popliteal pterygium syndrome (PPS). Van der Woude syndrome can include cleft lip and palate features along with dental anomalies and lip fistulas. In addition, common alleles in IRF6 have also been associated with non-syndromic cases of cleft lip and/or palate through genome-wide association studies and in many candidate gene studies. These disorders are caused by mutations in the IRF6 gene and some of the phenotypic heterogeneity is due to different types of IRF6 mutations. One explanation for this phenotypic variation between syndromes is based on a differential impact on the structure of the dimerized mutant proteins. VWS mutations appear to result in haploinsufficiency while PPS mutations may be dominant negative in nature. The spectrum of mutations in VWS and PPS has been recently summarized. IRF6 has been shown to play a critical role in keratinocyte development. A role for IRF6 in the common forms of cleft lip and palate has also been demonstrated and may explain ~20% of cases of cleft lip only. Variants in IRF6 have yielded consistent evidence of association with syndromic cleft and/or palate across multiple studies. A study by Birnbaum and colleagues in 2009 confirmed the impact of this gene on the etiology of cleft lip and/or palate, and the GENEVA Cleft Consortium study, which studied families from multiple populations, reconfirmed the findings that IRF6 mutations are strongly associated with cleft and/or palate. A role of IRF6 in causing cleft lip and/or palate is further supported by analysis of IRF6 mutant mice which exhibit a hyper-proliferative epidermis that fails to undergo terminal differentiation, leading to multiple epithelial adhesions that can occlude the oral cavity and result in cleft palate. Research on animal models indicate IRF6 determines keratinocyte proliferation and also has a key role in the formation of oral periderm. Recently, through utilization of mouse genetics, gene expression analyses, chromatin immunoprecipitation studies and luciferase reporter assays, it has been shown that IRF6 is a direct target of p63, which underlies several malformation syndromes that include cleft features, and p63 activates IRF6 transcription through the IRF6 enhancer element. Variation in the enhancer element increases susceptibility to cleft lip only. Both cleft lip with or without a cleft palate and cleft palate only features have been seen in families with an IRF6 mutation. In addition, different types of clefts can segregate within the same family.

See also

• Interferon regulatory factors

External links

• GeneReview/NIH/UW entry on IRF6-Related Disorders
• IRF6 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• IRF6 human gene location in the UCSC Genome Browser.
• IRF6 human gene details in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.