PAX9

Paired box gene 9, also known as PAX9, is a protein which in humans is encoded by the PAX9 gene.[5][6] It is also found in other mammals.[7]

PAX9
Identifiers
AliasesPAX9, STHAG3, paired box 9
External IDsOMIM: 167416 MGI: 97493 HomoloGene: 31360 GeneCards: PAX9
Gene location (Human)
Chr.Chromosome 14 (human)[1]
Band14q13.3Start36,657,568 bp[1]
End36,679,362 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

5083

18511

Ensembl

ENSG00000198807

ENSMUSG00000001497

UniProt

P55771

P47242

RefSeq (mRNA)

NM_006194
NM_001372076

NM_011041

RefSeq (protein)

NP_006185
NP_001359005

NP_035171

Location (UCSC)Chr 14: 36.66 – 36.68 MbChr 12: 56.69 – 56.71 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Expression and function

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.[8][9] Later on, Pax9 is also expressed in the axial skeleton.[8] Pax9 is required for craniofacial, tooth and limb development,[7][8] and may more generally involve development of stratified squamous epithelia as well as various organs and skeletal elements.[5] PAX9 plays a role in the absence of wisdom teeth in some human populations (possibly along with the less well studied AXIN2 and MSX1).[7]

Clinical significance

This gene was found amplified in lung cancer. The amplification covers three tissue developmental genes - TTF1, NKX2-8, and PAX9.[10] 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.

Oligodontia

Oligodontia is a genetic disorder caused by the mutation of the PAX9 gene. This disorder results in the congenital absence of 6 or more permanent teeth, with the exception of the third molar.[11] 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.[11] The gene PAX9 which can be found on chromosome 14 encodes a group of transcription factors that play an important role in early tooth development.[12] In humans, a frameshift mutation in the paired domain of PAX9 was discovered in those affected with oligodontia.[13] Multiple mechanisms are possible by which the mutation may arise. Recently, a study involving the missense mutation of a PAX9 gene suggests that the loss of function due to the absence DNA binding domain is a mechanism that causes oligodontia.[14] Those who express the PAX9 mutation and develop the disorder continue to have a normal life expectancy. Along with the mutation of the PAX9 gene, MSX1 gene mutations have also shown to affect dental development in fetuses.[14]

Interactions

PAX9 has been shown to interact with JARID1B.[15]

References

  1. GRCh38: Ensembl release 89: ENSG00000198807 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000001497 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: PAX9 paired box gene 9".
  6. 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. PMID 7981748. S2CID 21338655.
  7. Pereira TV, Salzano FM, Mostowska A, Trzeciak WH, Ruiz-Linares A, Chies JA, Saavedra C, Nagamachi C, Hurtado AM, Hill K, Castro-de-Guerra D, Silva-Júnior WA, Bortolini MC (April 2006). "Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development". Proceedings of the National Academy of Sciences of the United States of America. 103 (15): 5676–81. Bibcode:2006PNAS..103.5676P. doi:10.1073/pnas.0509562103. PMC 1458632. PMID 16585527.
  8. Peters H, Neubüser A, Kratochwil K, Balling R (September 1998). "Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities". Genes & Development. 12 (17): 2735–47. doi:10.1101/gad.12.17.2735. PMC 317134. PMID 9732271.
  9. 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. PMID 7649395.
  10. Kendall J, Liu Q, Bakleh A, Krasnitz A, Nguyen KC, Lakshmi B, Gerald WL, Powers S, Mu D (October 2007). "Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 104 (42): 16663–8. Bibcode:2007PNAS..10416663K. doi:10.1073/pnas.0708286104. PMC 2034240. PMID 17925434.
  11. 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. PMID 10615120. S2CID 27526349.
  12. Chi N, Epstein JA (January 2002). "Getting your Pax straight: Pax proteins in development and disease". Trends in Genetics. 18 (1): 41–7. doi:10.1016/s0168-9525(01)02594-x. PMID 11750700.
  13. Klein ML, Nieminen P, Lammi L, Niebuhr E, Kreiborg S (January 2005). "Novel mutation of the initiation codon of PAX9 causes oligodontia". Journal of Dental Research. 84 (1): 43–7. doi:10.1177/154405910508400107. PMID 15615874. S2CID 31928079.
  14. Jumlongras D, Lin JY, Chapra A, Seidman CE, Seidman JG, Maas RL, Olsen BR (February 2004). "A novel missense mutation in the paired domain of PAX9 causes non-syndromic oligodontia". Human Genetics. 114 (3): 242–9. doi:10.1007/s00439-003-1066-6. PMID 14689302. S2CID 12537564.
  15. Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS (June 2003). "Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9". The Journal of Biological Chemistry. 278 (23): 20507–13. doi:10.1074/jbc.M301994200. PMID 12657635.

Further reading

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