pax9 transcription factor


Summary: A paired box transcription factor that is involved in ODONTOGENESIS.

Top Publications

  1. Gerits A, Nieminen P, De Muynck S, Carels C. Exclusion of coding region mutations in MSX1, PAX9 and AXIN2 in eight patients with severe oligodontia phenotype. Orthod Craniofac Res. 2006;9:129-36 pubmed
    ..Recent evidence of PAX9-MSX1 protein interactions in odontogenesis as well as other genes and developmental factors should receive more attention. ..
  2. Tallon Walton V, Manzanares Céspedes M, Arte S, Carvalho Lobato P, Valdivia Gandur I, Garcia Susperregui A, et al. Identification of a novel mutation in the PAX9 gene in a family affected by oligodontia and other dental anomalies. Eur J Oral Sci. 2007;115:427-32 pubmed
    ..This fact underscores the importance that other presently unknown genes and developmental factors have in tooth development and in the etiology of dental anomalies. ..
  3. Nieminen P, Arte S, Tanner D, Paulin L, Alaluusua S, Thesleff I, et al. Identification of a nonsense mutation in the PAX9 gene in molar oligodontia. Eur J Hum Genet. 2001;9:743-6 pubmed
    ..The phenotype is presumably a consequence of haploinsufficiency of PAX9. In another Finnish family with molar tooth agenesis, we could not find similar sequence changes in PAX9. ..
  4. Neubüser A, Koseki H, Balling R. Characterization and developmental expression of Pax9, a paired-box-containing gene related to Pax1. Dev Biol. 1995;170:701-16 pubmed
    ..These results indicate that both Pax9 and -1 may act in parallel during morphogenesis of the vertebral column. ..
  5. Kapadia H, Frazier Bowers S, Ogawa T, D Souza R. Molecular characterization of a novel PAX9 missense mutation causing posterior tooth agenesis. Eur J Hum Genet. 2006;14:403-9 pubmed
    ..Based on our observed defects in DNA binding by the mutant protein, we propose a loss-of-function mechanism that contributes to haploinsufficiency of PAX9 in this family with posterior tooth agenesis. ..
  6. Lammi L, Halonen K, Pirinen S, Thesleff I, Arte S, Nieminen P. A missense mutation in PAX9 in a family with distinct phenotype of oligodontia. Eur J Hum Genet. 2003;11:866-71 pubmed
    ..A mutation of the homologous arginine of PAX6 has been shown to affect the target DNA specificity of PAX6. We suggest that a similar mechanism explains these distinct oligodontia phenotypes. ..
  7. Das P, Hai M, Elcock C, Leal S, Brown D, Brook A, et al. Novel missense mutations and a 288-bp exonic insertion in PAX9 in families with autosomal dominant hypodontia. Am J Med Genet A. 2003;118A:35-42 pubmed
    ..These studies extend the spectrum of mutations in PAX9 associated with hypodontia to include heretofore undescribed categories, including missense mutations. ..
  8. Paixão Côrtes V, Meyer D, Pereira T, Mazieres S, Elion J, Krishnamoorthy R, et al. Genetic variation among major human geographic groups supports a peculiar evolutionary trend in PAX9. PLoS ONE. 2011;6:e15656 pubmed publisher
    ..Exon 3 of PAX9 could be a good molecular example of how evolvability works. ..
  9. Paixão Côrtes V, Braga T, Salzano F, Mundstock K, Mundstock C, Bortolini M. PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis. Arch Oral Biol. 2011;56:337-44 pubmed publisher
    ..Common variants located out of the DNA binding domain of the two PAX9 and MSX1 genes can also be related to tooth agenesis. ..

More Information


  1. Stockton D, Das P, Goldenberg M, D Souza R, Patel P. Mutation of PAX9 is associated with oligodontia. Nat Genet. 2000;24:18-9 pubmed
  2. Vieira A, Meira R, Modesto A, Murray J. MSX1, PAX9, and TGFA contribute to tooth agenesis in humans. J Dent Res. 2004;83:723-7 pubmed
    ..No mutations were found in MSX1 or PAX9 coding regions. There were statistically significant data suggesting that MSX1 interacts with PAX9. These findings suggest that MSX1, PAX9, and TGFA play a role in isolated dental agenesis. ..
  3. Wang J, Jian F, Chen J, Wang H, Lin Y, Yang Z, et al. Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Arch Oral Biol. 2011;56:1027-34 pubmed publisher
    ..Our findings may imply that the PAX9 A240P mutation is a risk factor for oligodontia in the Chinese population. A240P is likely to be a genetic cause of oligodontia though previous literature suggested it as a polymorphism only. ..
  4. Pan Y, Wang L, Ma J, Zhang W, Wang M, Zhong W, et al. PAX9 polymorphisms and susceptibility to sporadic tooth agenesis: a case-control study in southeast China. Eur J Oral Sci. 2008;116:98-103 pubmed publisher
    ..These results suggest that the four PAX9 polymorphisms alone have a non-significant main effect on the risk of tooth agenesis but that the AGGC haplotype may have a protective effect associated with a decreased risk of tooth agenesis. ..
  5. Mise T, Iijima M, Inohaya K, Kudo A, Wada H. Function of Pax1 and Pax9 in the sclerotome of medaka fish. Genesis. 2008;46:185-92 pubmed publisher
    ..Two-month-old fish injected with Pax9 morpholino oligonucleotide showed abnormal morphology in the tail hypural skeletal element, which may have been related to this expression...
  6. Wang Y, Wu H, Wu J, Zhao H, Zhang X, Mues G, et al. Identification and functional analysis of two novel PAX9 mutations. Cells Tissues Organs. 2009;189:80-7 pubmed publisher
    ..Our finding that the severity of tooth agenesis in the patients was correlated to the DNA-binding capacity of the mutated PAX9 9proteins supports the hypothesis that DNA binding is responsible for the genetic defect. ..
  7. Peters H, Balling R. Teeth. Where and how to make them. Trends Genet. 1999;15:59-65 pubmed
    ..This cascade provides a molecular model by which reciprocal tissue interactions are controlled. ..
  8. Zhao J, Chen Y, Bao L, Xia Q, Wu T, Zhou L. [Novel mutations of PAX9 gene in Chinese patients with oligodontia]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2005;40:266-70 pubmed
    ..The results extend the spectrum of mutations in PAX9 gene associated with oligodontia. The novel mutations will play an important role in gene diagnosis of oligodontia. ..
  9. Frazier Bowers S, Guo D, Cavender A, Xue L, Evans B, King T, et al. A novel mutation in human PAX9 causes molar oligodontia. J Dent Res. 2002;81:129-33 pubmed
    ..Our results support the conclusion that molar oligodontia is due to allelic heterogeneity in PAX9, and these data further corroborate the role of PAX9 as an important regulator of molar development. ..
  10. Pawlowska E, Janik Papis K, Poplawski T, Blasiak J, Szczepanska J. Mutations in the PAX9 gene in sporadic oligodontia. Orthod Craniofac Res. 2010;13:142-52 pubmed publisher
    ..The IVS2-54A>G, IVS2-109G>C, and IVS2-41A>G mutations of the PAX9 gene may represent polymorphism associated with sporadic oligodontia. ..
  11. Mostowska A, Kobielak A, Trzeciak W. Molecular basis of non-syndromic tooth agenesis: mutations of MSX1 and PAX9 reflect their role in patterning human dentition. Eur J Oral Sci. 2003;111:365-70 pubmed
    ..This paper aims to review current literature about the molecular mechanisms responsible for selective tooth agenesis in humans. ..
  12. Hetzer Egger C, Schorpp M, Boehm T. Evolutionary conservation of gene structures of the Pax1/9 gene family. Biochim Biophys Acta. 2000;1492:517-21 pubmed
    ..AmphiPax1 is expressed in adult amphioxus in the pharyngeal endoderm. ..
  13. Klein M, Nieminen P, Lammi L, Niebuhr E, Kreiborg S. Novel mutation of the initiation codon of PAX9 causes oligodontia. J Dent Res. 2005;84:43-7 pubmed
    ..This is the first mutation found in the initiation codon of PAX9, and we suggest that it causes haploinsufficiency. ..
  14. Peres R, Scarel Caminaga R, do Espírito Santo A, Line S. Association between PAX-9 promoter polymorphisms and hypodontia in humans. Arch Oral Biol. 2005;50:861-71 pubmed
    ..These results indicate that polymorphisms in the promoter region of PAX 9 gene may have an influence on the transcriptional activity of this gene and are associated with hypodontia in humans. ..
  15. Hansen L, Kreiborg S, Jarlov H, Niebuhr E, Eiberg H. A novel nonsense mutation in PAX9 is associated with marked variability in number of missing teeth. Eur J Oral Sci. 2007;115:330-3 pubmed
    ..The family showed a marked phenotypic variability in the number of missing teeth, ranging from 2 to 15 missing teeth. The highest frequency of missing teeth was found for second molars followed by second premolars. ..
  16. Kim J, Simmer J, Lin B, Hu J. Novel MSX1 frameshift causes autosomal-dominant oligodontia. J Dent Res. 2006;85:267-71 pubmed
  17. Zhao J, Hu Q, Chen Y, Luo S, Bao L, Xu Y. A novel missense mutation in the paired domain of human PAX9 causes oligodontia. Am J Med Genet A. 2007;143A:2592-7 pubmed
    ..The R47W mutation dramatically reduced DNA binding suggesting that the mutant protein with consequent haploinsufficiency results in a clinical phenotype. ..
  18. Mostowska A, Kobielak A, Biedziak B, Trzeciak W. Novel mutation in the paired box sequence of PAX9 gene in a sporadic form of oligodontia. Eur J Oral Sci. 2003;111:272-6 pubmed
    ..Our results support the view that mutations in PAX9 could constitute a causative factor of oligodontia. We hypothesize that the G151A transition in PAX9 might be responsible for the sporadic form of tooth agenesis in this patient. ..
  19. Jumlongras D, Lin J, Chapra A, Seidman C, Seidman J, Maas R, et al. A novel missense mutation in the paired domain of PAX9 causes non-syndromic oligodontia. Hum Genet. 2004;114:242-9 pubmed
    ..The R28P mutation dramatically reduces DNA binding of the PAX9 paired domain and supports the hypothesis that loss of DNA binding is the pathogenic mechanism by which the mutation causes oligodontia. ..
  20. Santagati F, Abe K, Schmidt V, Schmitt John T, Suzuki M, Yamamura K, et al. Identification of Cis-regulatory elements in the mouse Pax9/Nkx2-9 genomic region: implication for evolutionary conserved synteny. Genetics. 2003;165:235-42 pubmed
    ..We propose such an intersecting organization of cis-regulatory sequences in multigenic regions as a possible mechanism that maintains evolutionary conserved synteny. ..
  21. De Coster P, Marks L, Martens L, Huysseune A. Dental agenesis: genetic and clinical perspectives. J Oral Pathol Med. 2009;38:1-17 pubmed publisher
    ..These new perspectives and future challenges in the field of identification of possible candidate genes involved in dental agenesis are discussed. ..
  22. Kula K, Trimmell J, Lu Y, Briscoe P, Feng J. Tooth agenesis in a family and homozygous PAX9 mutation in exon 3: a case report. World J Orthod. 2008;9:e55-61 pubmed
    ..The variable expression of tooth agenesis in this family suggests that clinicians should carefully examine all members of a family in which tooth agenesis is identified. ..
  23. Xuan K, Jin F, Liu Y, Yuan L, Wen L, Yang F, et al. Identification of a novel missense mutation of MSX1 gene in Chinese family with autosomal-dominant oligodontia. Arch Oral Biol. 2008;53:773-9 pubmed publisher
    ..347C>G. Our finding suggests the missense transversion (c.662C>A) and the polymorphisms (c.347C>G) may be responsible for oligodontia phenotype in this Chinese family. ..
  24. Wang Y, Groppe J, Wu J, Ogawa T, Mues G, D Souza R, et al. Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9. Hum Mol Genet. 2009;18:2863-74 pubmed publisher
    ..Our structure-based studies, which modeled DNA binding and subdomain stability, were able to predict functional consequences quite reliably. ..
  25. van den Boogaard M, Créton M, Bronkhorst Y, van der Hout A, Hennekam E, Lindhout D, et al. Mutations in WNT10A are present in more than half of isolated hypodontia cases. J Med Genet. 2012;49:327-31 pubmed publisher
    ..By including WNT10A in the DNA diagnostics of isolated tooth agenesis, the yield of molecular testing in this condition was significantly increased from 15% to 71%. ..
  26. Kriangkrai R, Iseki S, Eto K, Chareonvit S. Dual odontogenic origins develop at the early stage of rat maxillary incisor development. Anat Embryol (Berl). 2006;211:101-8 pubmed
    ..Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development. ..
  27. Das P, Stockton D, Bauer C, Shaffer L, D Souza R, Wright T, et al. Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia. Hum Genet. 2002;110:371-6 pubmed
    ..PAX9 is one of two genes, and the only odontogenic gene within the deletion interval, thus supporting the model of haploinsufficiency for PAX9 as the underlying basis for hypodontia. ..
  28. Peters H, Neubüser A, Balling R. Pax genes and organogenesis: Pax9 meets tooth development. Eur J Oral Sci. 1998;106 Suppl 1:38-43 pubmed
    ..Here, we briefly summarize our current knowledge about Pax genes and introduce Pax9 to the growing family of factors which are involved in tooth development. ..
  29. Pereira T, Salzano F, Mostowska A, Trzeciak W, Ruiz Linares A, Chies J, et al. Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development. Proc Natl Acad Sci U S A. 2006;103:5676-81 pubmed
    ..New World and Old World primate lineages may, however, have different degrees of restriction for changes in this DNA region...
  30. Stock D, Jackman W, Trapani J. Developmental genetic mechanisms of evolutionary tooth loss in cypriniform fishes. Development. 2006;133:3127-37 pubmed publisher
    ..We hypothesize that a loss of Fgf signaling to oral epithelium was associated with cypriniform tooth loss...
  31. Peters H, Doll U, Niessing J. Differential expression of the chicken Pax-1 and Pax-9 gene: in situ hybridization and immunohistochemical analysis. Dev Dyn. 1995;203:1-16 pubmed
    ..Furthermore, chPax-9 gene products are detected in circumscribed areas of mesenchyme in the metatarsus and in entodermal derivatives, i.e., in the lining epithelium of the developing pharynx and of the embryonic and adult esophagus. ..
  32. Seo Y, Park J, Kim Y, Baek S. Associations between the risk of tooth agenesis and single-nucleotide polymorphisms of MSX1 and PAX9 genes in nonsyndromic cleft patients. Angle Orthod. 2013;83:1036-42 pubmed publisher
    ..05). Genetic disturbances of MSX1 and PAX9 genes are associated with tooth agenesis within and outside the cleft area. ..
  33. Slayton R, Williams L, Murray J, Wheeler J, Lidral A, Nishimura C. Genetic association studies of cleft lip and/or palate with hypodontia outside the cleft region. Cleft Palate Craniofac J. 2003;40:274-9 pubmed
    ..Cleft lip and/or palate with hypodontia outside the cleft region was positively associated with both TGFB3 and MSX1, compared with noncleft controls. ..
  34. Rodrigo I, Hill R, Balling R, Munsterberg A, Imai K. Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development. 2003;130:473-82 pubmed
    ..These results strongly suggest that Bapx1 is a direct target of Pax1 and Pax9. Together, we conclude that Pax1 and Pax9 are required and sufficient for the chondrogenic differentiation of sclerotomal cells. ..
  35. Gerber J, Richter T, Kremmer E, Adamski J, Hofler H, Balling R, et al. Progressive loss of PAX9 expression correlates with increasing malignancy of dysplastic and cancerous epithelium of the human oesophagus. J Pathol. 2002;197:293-7 pubmed
    ..These data suggest that upregulated PAX9 expression is not required for the formation of the majority of squamous cell carcinomas of the human oesophagus. ..
  36. Ikegawa S, Mabuchi A, Ogawa M, Ikeda T. Allele-specific PCR amplification due to sequence identity between a PCR primer and an amplicon: is direct sequencing so reliable?. Hum Genet. 2002;110:606-8 pubmed
    ..Sequence similarity between PCR primers and internal amplified regions should be considered for all methods for mutation detection and genotyping using PCR. ..
  37. Farley A, Morris L, Vroegindeweij E, Depreter M, Vaidya H, Stenhouse F, et al. Dynamics of thymus organogenesis and colonization in early human development. Development. 2013;140:2015-26 pubmed publisher
  38. Stapleton P, Weith A, Urbanek P, Kozmik Z, Busslinger M. Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9. Nat Genet. 1993;3:292-8 pubmed
    ..PAX-1 and PAX-7 map to chromosomal regions containing previously assigned disease loci. ..
  39. Hol F, Geurds M, Chatkupt S, Shugart Y, Balling R, Schrander Stumpel C, et al. PAX genes and human neural tube defects: an amino acid substitution in PAX1 in a patient with spina bifida. J Med Genet. 1996;33:655-60 pubmed
    ..Our findings so far do not support a major role of the PAX genes examined in the aetiology of NTD. However, the detection of a mutation in PAX1 suggests that, in principle, this gene can act as a risk factor for human NTD. ..
  40. Almeida C, Andrade S, Saito C, Ramenzoni L, Line S. Transcriptional analysis of the human PAX9 promoter. J Appl Oral Sci. 2010;18:482-6 pubmed
    ..The present results suggest that the promoter sequences analyzed are not sufficient to drive PAX9 gene transcription. ..
  41. Alves Ferreira M, Pinho T, Sousa A, Sequeiros J, Lemos C, Alonso I. Identification of genetic risk factors for maxillary lateral incisor agenesis. J Dent Res. 2014;93:452-8 pubmed publisher
    ..We report the first evidence of the involvement of sprouty genes in MLIA susceptibility. This large study results in a better understanding of the genetic components and mechanisms underlying this trait. ..
  42. Fraser G, Britz R, Hall A, Johanson Z, Smith M. Replacing the first-generation dentition in pufferfish with a unique beak. Proc Natl Acad Sci U S A. 2012;109:8179-84 pubmed publisher
    ..We conclude that even highly derived morphological structures like the pufferfish beak form via a conserved developmental bauplan capable of modification during ontogeny by subtle respecification of the developmental module. ..
  43. Xiao L, Tsutsui T. Three-dimensional epithelial and mesenchymal cell co-cultures form early tooth epithelium invagination-like structures: expression patterns of relevant molecules. J Cell Biochem. 2012;113:1875-85 pubmed publisher
    ..This model might be explored as a potential research tool for epithelial-mesenchymal interaction and tooth regeneration. ..
  44. Nornes S, Mikkola I, Krauss S, Delghandi M, Perander M, Johansen T. Zebrafish Pax9 encodes two proteins with distinct C-terminal transactivating domains of different potency negatively regulated by adjacent N-terminal sequences. J Biol Chem. 1996;271:26914-23 pubmed
  45. Mues G, Kapadia H, Wang Y, D Souza R. Genetics and human malformations. J Craniofac Surg. 2009;20 Suppl 2:1652-4 pubmed publisher
    ..In this report, we briefly review the roles of the PAX9, MSX1, AXIN2, and EDA genes in the causation of congenital tooth agenesis and the promise of molecular genetic research for the improvement of patient care. ..
  46. Chen Y, Zhang Y, Jiang T, Barlow A, St Amand T, Hu Y, et al. Conservation of early odontogenic signaling pathways in Aves. Proc Natl Acad Sci U S A. 2000;97:10044-9 pubmed
  47. Hsu D, Acharya C, Balakumaran B, Riedel R, Kim M, Stevenson M, et al. Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer. Proc Natl Acad Sci U S A. 2009;106:5312-7 pubmed publisher
    ..This suggests that the cohort of patients with coactivation of TTF-1 and NKX2-8 pathways appears to be resistant to standard cisplatin therapy, suggesting the need for alternative therapies in this cohort of high-risk patients. ..
  48. Camilleri S. Maxillary canine anomalies and tooth agenesis. Eur J Orthod. 2005;27:450-6 pubmed
    ..The prevalence of lower second premolar (5 per cent) and M.3 (27.5 per cent) agenesis approached reference values. Evidence for the implication of the MSX1 or PAX9 genes in the aetiology of PDC was weak. ..
  49. Devos D, Vuillaume I, de Becdelievre A, de Martinville B, Dhaenens C, Cuvellier J, et al. New syndromic form of benign hereditary chorea is associated with a deletion of TITF-1 and PAX-9 contiguous genes. Mov Disord. 2006;21:2237-40 pubmed
    ..Associated signs, sometimes of slight expression, remain of high interest for the clinical and genetic diagnosis of benign hereditary chorea. ..
  50. Peters H, Wilm B, Sakai N, Imai K, Maas R, Balling R. Pax1 and Pax9 synergistically regulate vertebral column development. Development. 1999;126:5399-408 pubmed
    ..In addition, our data indicate that the development of medial and lateral elements of vertebrae is regulated by distinct genetic pathways. ..
  51. Revest J, Suniara R, Kerr K, Owen J, Dickson C. Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J Immunol. 2001;167:1954-61 pubmed
    ..Nevertheless, sufficient epithelial cell differentiation occurs in the severely hypoplastic thymus to allow the development of CD4/CD8-double-positive thymocytes and a very small number of single-positive thymocytes expressing TCRs. ..
  52. Hetzer Egger C, Schorpp M, Haas Assenbaum A, Balling R, Peters H, Boehm T. Thymopoiesis requires Pax9 function in thymic epithelial cells. Eur J Immunol. 2002;32:1175-81 pubmed
    ..Whereas expression of TCRbeta chain genes is readily detectable in the mutant thymus, no expression of the TCRgamma chain was detectable. Our results identify a new genetically defined control point of thymopoiesis. ..
  53. Kobus K, Ammar D, Nazari E, Müller Y. Homocysteine causes disruptions in spinal cord morphology and changes the expression of Pax 1/9 and Sox 9 gene products in the axial mesenchyme. Birth Defects Res A Clin Mol Teratol. 2013;97:386-97 pubmed publisher
    ..Our data clarified the relationship between spinal NTD genesis and disruptions of Pax 1/9 and Sox 9 gene products in the axial mesenchyme caused by the FA/Hcy imbalance. ..