This gene is a member of the paired box (PAX) family of transcription factors. During mouse embryogenesis Pax9 expression starts from embryonic day 8.5 and becomes more evident by E9.5; at this stage its expression is restricted to the pharyngeal endoderm. Later on, Pax9 is also expressed in the axial skeleton. Pax9 is required for craniofacial, tooth and limb development, and may more generally involve development of stratified squamous epithelia as well as various organs and skeletal elements. PAX9 plays a role in the absence of wisdom teeth in some human populations (possibly along with the less well studied AXIN2 and MSX1).
This gene was found amplified in lung cancer. The amplification covers three tissue developmental genes - TTF1, NKX2-8, and PAX9. It appears that certain lung cancer cells select for DNA copy number amplification and increased RNA/protein expression of these three coamplified genes for functional advantages.
A genetic disorder caused by the mutation of the PAX 9 gene. This disorder results in the congenital absence of 6 or more permanent teeth, with the exception of the third molar. Also known as selective tooth agenesis (STHAG), it is the most common disorder in regard to human dentition, affecting a little less than one fourth of the population. The gene PAX 9 which can be found on chromosome 14 encodes a group of transcription factors that play an important role in early tooth development. In humans, a frameshift mutation in the paired domain of PAX 9 was discovered in those affected with oligodontia. Multiple mechanisms are possible by which the mutation may arise. Recently, a study involving the missense mutation of a PAX 9 gene suggests that the loss of function due to the absence DNA binding domain is a mechanism that causes oligodontia. Those who express the PAX 9 mutation and develop the disorder continue to have a normal life expectancy. Along with the mutation of the PAX 9 gene, MSX1 gene mutations have also shown to affect dental development in fetuses.
^Stapleton P, Weith A, Urbánek P, Kozmik Z, Busslinger M (April 1993). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9". Nature Genetics. 3 (4): 292–8. doi:10.1038/ng0493-292. PMID7981748.
^Neubüser A, Koseki H, Balling R (August 1995). "Characterization and developmental expression of Pax9, a paired-box-containing gene related to Pax1". Developmental Biology. 170 (2): 701–16. doi:10.1006/dbio.1995.1248. PMID7649395.
Kobielak A, Kobielak K, Wiśniewski AS, Mostowska A, Biedziak B, Trzeciak WH (2001). "The novel polymorphic variants within the paired box of the PAX9 gene are associated with selective tooth agenesis". Folia Histochemica et Cytobiologica. 39 (2): 111–2. PMID11374781.
Bannykh SI, Emery SC, Gerber JK, Jones KL, Benirschke K, Masliah E (July 2003). "Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review". American Journal of Medical Genetics. Part A. 120A (2): 241–6. doi:10.1002/ajmg.a.20192. PMID12833407.
Peters H, Schuster G, Neubüser A, Richter T, Höfler H, Balling R (January 1997). "Isolation of the Pax9 cDNA from adult human esophagus". Mammalian Genome. 8 (1): 62–4. doi:10.1007/s003359900351. PMID9021154.
Stockton DW, Das P, Goldenberg M, D'Souza RN, Patel PI (January 2000). "Mutation of PAX9 is associated with oligodontia". Nature Genetics. 24 (1): 18–9. doi:10.1038/71634. PMID10615120.
Hetzer-Egger C, Schorpp M, Boehm T (July 2000). "Evolutionary conservation of gene structures of the Pax1/9 gene family". Biochimica et Biophysica Acta. 1492 (2-3): 517–21. doi:10.1016/s0167-4781(00)00130-5. PMID10899593.
Nieminen P, Arte S, Tanner D, Paulin L, Alaluusua S, Thesleff I, Pirinen S (October 2001). "Identification of a nonsense mutation in the PAX9 gene in molar oligodontia". European Journal of Human Genetics. 9 (10): 743–6. doi:10.1038/sj.ejhg.5200715. PMID11781684.
Das P, Stockton DW, Bauer C, Shaffer LG, D'Souza RN, Wright T, Patel PI (April 2002). "Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia". Human Genetics. 110 (4): 371–6. doi:10.1007/s00439-002-0699-1. PMID11941488.
Ikegawa S, Mabuchi A, Ogawa M, Ikeda T (June 2002). "Allele-specific PCR amplification due to sequence identity between a PCR primer and an amplicon: is direct sequencing so reliable?". Human Genetics. 110 (6): 606–8. doi:10.1007/s00439-002-0735-1. PMID12107448.
Gerber JK, Richter T, Kremmer E, Adamski J, Höfler H, Balling R, Peters H (July 2002). "Progressive loss of PAX9 expression correlates with increasing malignancy of dysplastic and cancerous epithelium of the human oesophagus". The Journal of Pathology. 197 (3): 293–7. doi:10.1002/path.1115. PMID12115874.
Peck S, Peck L, Kataja M (December 2002). "Concomitant occurrence of canine malposition and tooth agenesis: evidence of orofacial genetic fields". American Journal of Orthodontics and Dentofacial Orthopedics. 122 (6): 657–60. doi:10.1067/mod.2002.129915. PMID12490878.
Mostowska A, Kobielak A, Biedziak B, Trzeciak WH (June 2003). "Novel mutation in the paired box sequence of PAX9 gene in a sporadic form of oligodontia". European Journal of Oral Sciences. 111 (3): 272–6. doi:10.1034/j.1600-0722.2003.00036.x. PMID12786960.
Lammi L, Halonen K, Pirinen S, Thesleff I, Arte S, Nieminen P (November 2003). "A missense mutation in PAX9 in a family with distinct phenotype of oligodontia". European Journal of Human Genetics. 11 (11): 866–71. doi:10.1038/sj.ejhg.5201060. PMID14571272.
Mensah JK, Ogawa T, Kapadia H, Cavender AC, D'Souza RN (February 2004). "Functional analysis of a mutation in PAX9 associated with familial tooth agenesis in humans". The Journal of Biological Chemistry. 279 (7): 5924–33. doi:10.1074/jbc.M305648200. PMID14607846.