Gene Symbol: Irf6
Description: interferon regulatory factor 6
Alias: AI876454, E230028I05Rik, mirf6, interferon regulatory factor 6, IRF-6
Species: mouse
Products:     Irf6

Top Publications

  1. Thomason H, Zhou H, Kouwenhoven E, Dotto G, Restivo G, Nguyen B, et al. Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice. J Clin Invest. 2010;120:1561-9 pubmed publisher
    ..Mutations in the transcription factor-encoding genes p63 and interferon regulatory factor 6 (IRF6) have individually been identified as causes of cleft palate; however, a relationship between ..
  2. Restivo G, Nguyen B, Dziunycz P, Ristorcelli E, Ryan R, Özuysal Ö, et al. IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes. EMBO J. 2011;30:4571-85 pubmed publisher
    ..We report here that interferon regulatory factor 6 (IRF6), an IRF family member with an essential role in epidermal development, is induced in ..
  3. Bailey C, Margaryan N, Abbott D, Schutte B, Yang B, Khalkhali Ellis Z, et al. Temporal and spatial expression patterns for the tumor suppressor Maspin and its binding partner interferon regulatory factor 6 during breast development. Dev Growth Differ. 2009;51:473-81 pubmed publisher
    b>Interferon regulatory factor 6 (IRF6) is a non-canonical member of the interferon regulatory factor family of transcription factors. We recently identified IRF6 as a novel Maspin-interacting protein in mammary epithelial cells...
  4. Richardson R, Dixon J, Jiang R, Dixon M. Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence. Hum Mol Genet. 2009;18:2632-42 pubmed publisher
    ..In humans, mutations in the transcription factor interferon regulatory factor 6 (IRF6) underlie Van der Woude syndrome and popliteal pterygium syndrome...
  5. Little H, Rorick N, Su L, Baldock C, Malhotra S, Jowitt T, et al. Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6. Hum Mol Genet. 2009;18:535-45 pubmed publisher
    ..CLP, lip pits, skin-folds, syndactyly and oral adhesions which arise as the result of mutations in interferon regulatory factor 6 (IRF6)...
  6. Richardson R, Dixon J, Malhotra S, Hardman M, Knowles L, Boot Handford R, et al. Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat Genet. 2006;38:1329-34 pubmed
    ..Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and ..
  7. Fakhouri W, Rhea L, Du T, Sweezer E, Morrison H, Fitzpatrick D, et al. MCS9.7 enhancer activity is highly, but not completely, associated with expression of Irf6 and p63. Dev Dyn. 2012;241:340-9 pubmed publisher
    DNA variation in Interferon Regulatory Factor 6 (IRF6) contributes risk for orofacial clefting, including a common DNA variant rs642961. This DNA variant is located in a multi-species conserved sequence that is 9...
  8. Bailey C, Abbott D, Margaryan N, Khalkhali Ellis Z, Hendrix M. Interferon regulatory factor 6 promotes cell cycle arrest and is regulated by the proteasome in a cell cycle-dependent manner. Mol Cell Biol. 2008;28:2235-43 pubmed publisher
    b>Interferon regulatory factor 6 (IRF6) is a novel and unique member of the IRF family of transcription factors...
  9. Moretti F, Marinari B, Lo Iacono N, Botti E, Giunta A, Spallone G, et al. A regulatory feedback loop involving p63 and IRF6 links the pathogenesis of 2 genetically different human ectodermal dysplasias. J Clin Invest. 2010;120:1570-7 pubmed publisher
    ..Mutations in the p63 and interferon regulatory factor 6 (IRF6) genes have been found in human patients with these syndromes, consistent with phenotypes...

More Information


  1. Rahimov F, Marazita M, Visel A, Cooper M, Hitchler M, Rubini M, et al. Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet. 2008;40:1341-7 pubmed publisher
    ..nonsyndromic cleft lip with or without cleft palate (NSCL/P) is strongly associated with SNPs in IRF6 (interferon regulatory factor 6)...
  2. Ingraham C, Kinoshita A, Kondo S, Yang B, Sajan S, Trout K, et al. Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet. 2006;38:1335-40 pubmed
    ..Mice deficient for Irf6 have not been reported, but in humans, mutations in IRF6 cause two mendelian orofacial clefting syndromes, and ..
  3. Xu X, Han J, Ito Y, Bringas P, Urata M, Chai Y. Cell autonomous requirement for Tgfbr2 in the disappearance of medial edge epithelium during palatal fusion. Dev Biol. 2006;297:238-48 pubmed
    ..At the molecular level, Tgfb3 and Irf6 have similar expression patterns in the MEE...
  4. Knight A, Schutte B, Jiang R, Dixon M. Developmental expression analysis of the mouse and chick orthologues of IRF6: the gene mutated in Van der Woude syndrome. Dev Dyn. 2006;235:1441-7 pubmed
    ..VWS arises as the result of mutations in the gene encoding interferon regulatory factor 6 (IRF6)...
  5. Kondo S, Schutte B, Richardson R, Bjork B, Knight A, Watanabe Y, et al. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet. 2002;32:285-9 pubmed
    b>Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain...
  6. Aerts A, Devolder I, Weinberg S, Thedens D, Dunnwald M, Schutte B, et al. Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in the mouse. Am J Med Genet A. 2014;164A:655-60 pubmed publisher
    ..Among many genetic contributors to orofacial clefting, Interferon Regulatory Factor 6 (IRF6) is unique since mutations in this gene cause Van der Woude (VWS), the most common clefting ..
  7. Ferretti E, Li B, Zewdu R, Wells V, Hebert J, Karner C, et al. A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Dev Cell. 2011;21:627-41 pubmed publisher
    ..Mutations of WNT, P63, and IRF6 yield CL/P in humans and mice; however, how these genes are regulated remains elusive...
  8. Chin S, Romano R, Nagarajan P, Sinha S, Garrett Sinha L. Aberrant epidermal differentiation and disrupted ?Np63/Notch regulatory axis in Ets1 transgenic mice. Biol Open. 2013;2:1336-45 pubmed publisher
    ..Given the established tumor suppressive role for Notch signaling in skin tumorigenesis, the demonstrated ability of Ets1 to interfere with this signaling pathway may be important in mediating its pro-tumorigenic activities. ..
  9. Stottmann R, Bjork B, Doyle J, Beier D. Identification of a Van der Woude syndrome mutation in the cleft palate 1 mutant mouse. Genesis. 2010;48:303-8 pubmed publisher
    Mutations in Interferon Regulatory Factor 6 (IRF6) have been identified in two human allelic syndromes with cleft lip and/or palate: Van der Woude (VWS) and Popliteal Pterygium syndromes (PPS)...
  10. Chen Y, Perry D, Boackle S, Sobel E, Molina H, Croker B, et al. Several genes contribute to the production of autoreactive B and T cells in the murine lupus susceptibility locus Sle1c. J Immunol. 2005;175:1080-9 pubmed
  11. Ke C, Xiao W, Chen C, Lo L, Wong F. IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion. Sci Rep. 2015;5:12791 pubmed publisher
    Mutation in interferon regulatory factor 6 (IRF6) is known to cause syndromic and non-syndromic cleft lip/palate in human...
  12. Leslie E, Taub M, Liu H, Steinberg K, Koboldt D, Zhang Q, et al. Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2, and NOG by targeted sequencing of GWAS loci. Am J Hum Genet. 2015;96:397-411 pubmed publisher
    ..This targeted sequencing study provides strong functional evidence implicating several specific variants as primary contributory risk alleles for nonsyndromic clefting in humans. ..
  13. Fakhouri W, Rahimov F, Attanasio C, Kouwenhoven E, Ferreira De Lima R, Felix T, et al. An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects. Hum Mol Genet. 2014;23:2711-20 pubmed publisher
    DNA variation in Interferon Regulatory Factor 6 (IRF6) causes Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate (CLP). However, an etiologic variant in IRF6 has been found in only 70% of VWS families...
  14. Iwata J, Suzuki A, Pelikan R, Ho T, Sanchez Lara P, Urata M, et al. Smad4-Irf6 genetic interaction and TGF?-mediated IRF6 signaling cascade are crucial for palatal fusion in mice. Development. 2013;140:1220-30 pubmed publisher
    ..mutations in the genes encoding transforming growth factor beta (TGF?) signaling molecules and interferon regulatory factor 6 (Irf6) have been identified as genetic risk factors for cleft palate, little is known about the ..
  15. Biggs L, Rhea L, Schutte B, Dunnwald M. Interferon regulatory factor 6 is necessary, but not sufficient, for keratinocyte differentiation. J Invest Dermatol. 2012;132:50-8 pubmed publisher
    ..b>Interferon Regulatory Factor 6 (Irf6)-deficient mice die perinatally and exhibit ectopic proliferation and defective epidermal ..
  16. Kousa Y, Moussa D, Schutte B. IRF6 expression in basal epithelium partially rescues Irf6 knockout mice. Dev Dyn. 2017;246:670-681 pubmed publisher
    Mutations in IRF6, CHUK (IKKA), and RIPK4 can lead to a disease spectrum that includes cutaneous, limb, and craniofacial malformations...
  17. Richardson R, Hammond N, Coulombe P, Saloranta C, Nousiainen H, Salonen R, et al. Periderm prevents pathological epithelial adhesions during embryogenesis. J Clin Invest. 2014;124:3891-900 pubmed publisher
    ..Mice carrying loss-of-function mutations in the genes encoding IFN regulatory factor 6 (IRF6), IκB kinase-α (IKKα), and stratifin (SFN) exhibit abnormal epidermal development, and we determined that ..
  18. Letra A, Fakhouri W, Fonseca R, Menezes R, Kempa I, Prasad J, et al. Interaction between IRF6 and TGFA genes contribute to the risk of nonsyndromic cleft lip/palate. PLoS ONE. 2012;7:e45441 pubmed publisher
    Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact...
  19. Tamasas B, Cox T. Massively Increased Caries Susceptibility in an Irf6 Cleft Lip/Palate Model. J Dent Res. 2017;96:315-322 pubmed publisher
    ..Using a conditional targeting approach, we ablated the major CLP gene Irf6 only in the late embryonic oral epithelium ( Irf6 cKO), bypassing the role of the gene in lip and palate ..
  20. Kawasaki M, Kawasaki K, Oommen S, Blackburn J, Watanabe M, Nagai T, et al. Regional regulation of Filiform tongue papillae development by Ikk?/Irf6. Dev Dyn. 2016;245:937-46 pubmed publisher
    ..We found Ikk? and Irf6 expression in developing tongue epithelium, and describe here specific tongue abnormalities in mice with mutation ..
  21. Ding H, Wu X, Bostrom H, Kim I, Wong N, Tsoi B, et al. A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling. Nat Genet. 2004;36:1111-6 pubmed
    ..Our results also show that PDGF-C signaling is a new pathway in palatogenesis, different from, and independent of, those previously implicated. ..
  22. Leslie E, Mansilla M, Biggs L, Schuette K, Bullard S, Cooper M, et al. Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the cleft lip with or without cleft palate locus identified by genome-wide association on chromosome 1p22. Birth Defects Res A Clin Mol Teratol. 2012;94:934-42 pubmed publisher
    ..Arhgap29 showed craniofacial expression and was reduced in a mouse deficient for Irf6, a gene previously shown to have a critical role in craniofacial development...
  23. Murray S, Oram K, Gridley T. Multiple functions of Snail family genes during palate development in mice. Development. 2007;134:1789-97 pubmed
  24. Stottmann R, Moran J, Turbe Doan A, Driver E, Kelley M, Beier D. Focusing forward genetics: a tripartite ENU screen for neurodevelopmental mutations in the mouse. Genetics. 2011;188:615-24 pubmed publisher
    ..We find that refining ENU mutagenesis in these ways is an efficient experimental approach and that investigation of the developing mammalian nervous system using forward genetic experiments is highly productive. ..
  25. Peyrard Janvid M, Leslie E, Kousa Y, Smith T, Dunnwald M, Magnusson M, et al. Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development. Am J Hum Genet. 2014;94:23-32 pubmed publisher
    Mutations in interferon regulatory factor 6 (IRF6) account for ?70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate...
  26. Li C, Ying W, Huang Z, Brehm T, Morin A, Vella A, et al. IRF6 Regulates Alternative Activation by Suppressing PPAR? in Male Murine Macrophages. Endocrinology. 2017;158:2837-2847 pubmed publisher
    ..This study demonstrates a critical role for interferon regulatory factor 6 (IRF6) in regulating macrophage M2 activation by suppressing peroxisome proliferator-activated ..
  27. Jin J, Li Q, Higashi Y, Darling D, Ding J. Analysis of Zfhx1a mutant mice reveals palatal shelf contact-independent medial edge epithelial differentiation during palate fusion. Cell Tissue Res. 2008;333:29-38 pubmed publisher
    ..5 in a contact-independent manner, suggesting that differentiation of the medial edge epithelium was largely programmed through an intrinsic mechanism within the palate shelf. ..
  28. Biggs L, Naridze R, DeMali K, Lusche D, Kuhl S, Soll D, et al. Interferon regulatory factor 6 regulates keratinocyte migration. J Cell Sci. 2014;127:2840-8 pubmed publisher
    b>Interferon regulatory factor 6 (Irf6) regulates keratinocyte proliferation and differentiation. In this study, we tested the hypothesis that Irf6 regulates cellular migration and adhesion. Irf6-deficient embryos at 10...
  29. Kurosaka H, Iulianella A, Williams T, Trainor P. Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis. J Clin Invest. 2014;124:1660-71 pubmed publisher
    ..Moreover, reduction of canonical WNT signaling perturbed p63/interferon regulatory factor 6 (p63/IRF6) signaling, resulting in increased proliferation and decreased cell death, which was ..
  30. Goudy S, Angel P, Jacobs B, Hill C, Mainini V, Smith A, et al. Cell-autonomous and non-cell-autonomous roles for IRF6 during development of the tongue. PLoS ONE. 2013;8:e56270 pubmed publisher
    b>Interferon regulatory factor 6 (IRF6) encodes a highly conserved helix-turn-helix DNA binding protein and is a member of the interferon regulatory family of DNA transcription factors...
  31. Mollo M, Antonini D, Mitchell K, Fortugno P, Costanzo A, Dixon J, et al. p63-dependent and independent mechanisms of nectin-1 and nectin-4 regulation in the epidermis. Exp Dermatol. 2015;24:114-9 pubmed publisher
    ..Pvrl4 expression was similarly affected, in parallel with decreased expression of the transcription factor Irf6. Consistent with the well-characterized role of Irf6 in keratinocyte differentiation and its strong downregulation ..
  32. Rorick N, Kinoshita A, Weirather J, Peyrard Janvid M, de Lima R, Dunnwald M, et al. Genomic strategy identifies a missense mutation in WD-repeat domain 65 (WDR65) in an individual with Van der Woude syndrome. Am J Med Genet A. 2011;155A:1314-21 pubmed publisher
    Genetic variation in the transcription factor interferon regulatory factor 6 (IRF6) causes and contributes risk for oral clefting disorders. We hypothesized that genes regulated by IRF6 are also involved in oral clefting disorders...
  33. Noda K, Mishina Y, Komatsu Y. Constitutively active mutation of ACVR1 in oral epithelium causes submucous cleft palate in mice. Dev Biol. 2016;415:306-313 pubmed publisher
    ..Our study provides a new insight into the etiology of SMCP caused by augmented BMP signaling. ..
  34. Blackburn J, Ohazama A, Kawasaki K, Otsuka Tanaka Y, Liu B, Honda K, et al. The role of Irf6 in tooth epithelial invagination. Dev Biol. 2012;365:61-70 pubmed publisher
    ..We show here that mutation of the Interferon regulatory factor (Irf) family, Irf6 also results in evagination of incisor epithelium...
  35. Joly S, Rhea L, Volk P, Moreland J, Dunnwald M. Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock. PLoS ONE. 2016;11:e0152385 pubmed publisher
    ..b>Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and ..
  36. Anderson K, White P, Kaestner K, Sussel L. Identification of known and novel pancreas genes expressed downstream of Nkx2.2 during development. BMC Dev Biol. 2009;9:65 pubmed publisher
    ..2 in maintaining appropriate exocrine gene expression. Most importantly, Nkx2.2 appears to function within a complex regulatory loop with Ngn3 at a key endocrine differentiation step. ..
  37. Hou M, Cao J, Chen B, Liu X. Down-Regulation of IRF6 Protects Cortical Neurons Against Traumatic Neuronal Injury Through Activating Akt-eNOS Pathway. Cell Mol Neurobiol. 2017;37:587-594 pubmed publisher
    b>Interferon regulatory factor 6 (IRF6) is a novel and unique member of the IRF family of transcription factors, and the regulation and function of IRF6 remain unknown...
  38. Kousa Y, Roushangar R, Patel N, Walter A, Marangoni P, Krumlauf R, et al. IRF6 and SPRY4 Signaling Interact in Periderm Development. J Dent Res. 2017;96:1306-1313 pubmed publisher
    Rare mutations in IRF6 and GRHL3 cause Van der Woude syndrome, an autosomal dominant orofacial clefting disorder. Common variants in IRF6 and GRHL3 also contribute risk for isolated orofacial clefting...
  39. Chu E, Tamasas B, Fong H, Foster B, LaCourse M, Tran A, et al. Full Spectrum of Postnatal Tooth Phenotypes in a Novel Irf6 Cleft Lip Model. J Dent Res. 2016;95:1265-73 pubmed publisher
    ..To address this, the authors generated a unique conditional knockout model involving the major CLP gene, Irf6, that overcomes the previously reported perinatal lethality to enable assessment of any posteruption dental ..
  40. Smith A, Kousa Y, Kinoshita A, Fodor K, Yang B, Schutte B. Generation and characterization of a conditional allele of Interferon Regulatory Factor 6. Genesis. 2017;55: pubmed publisher
    b>Interferon Regulatory Factor 6 (IRF6) is a critical regulator of differentiation, proliferation, and migration of keratinocytes...
  41. Lane J, Yumoto K, Azhar M, Ninomiya Tsuji J, Inagaki M, Hu Y, et al. Tak1, Smad4 and Trim33 redundantly mediate TGF-β3 signaling during palate development. Dev Biol. 2015;398:231-41 pubmed publisher
    ..To conclude, our data reveal added complexity in TGF-β signaling during palatogenesis and demonstrate that functionally redundant pathways involving Smad4, Tak1 and Trim33 regulate palatal epithelial fusion. ..