PAX9

Last updated
PAX9
Identifiers
Aliases PAX9 , STHAG3, paired box 9
External IDs OMIM: 167416; MGI: 97493; HomoloGene: 31360; GeneCards: PAX9; OMA:PAX9 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006194
NM_001372076

NM_011041

RefSeq (protein)

NP_006185
NP_001359005

NP_035171

Location (UCSC) Chr 14: 36.66 – 36.68 Mb Chr 12: 56.74 – 56.76 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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]

Related Research Articles

Hypodontia is defined as the developmental absence of one or more teeth excluding the third molars. It is one of the most common dental anomalies, and can have a negative impact on function, and also appearance. It rarely occurs in primary teeth and the most commonly affected are the adult second premolars and the upper lateral incisors. It usually occurs as part of a syndrome that involves other abnormalities and requires multidisciplinary treatment.

<span class="mw-page-title-main">Pax genes</span> Family of transcription factors

In evolutionary developmental biology, Paired box (Pax) genes are a family of genes coding for tissue specific transcription factors containing an N-terminal paired domain and usually a partial, or in the case of four family members, a complete homeodomain to the C-terminus. An octapeptide as well as a Pro-Ser-Thr-rich C terminus may also be present. Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.

<span class="mw-page-title-main">PAX6</span> Protein-coding gene in humans

Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the PAX6 gene.

<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">TCF4</span> Protein-coding gene in the species Homo sapiens

Transcription factor 4 (TCF-4) also known as immunoglobulin transcription factor 2 (ITF-2) is a protein that in humans is encoded by the TCF4 gene located on chromosome 18q21.2.

<span class="mw-page-title-main">PAX2</span> Protein-coding gene in humans

Paired box gene 2, also known as Pax-2, is a protein which in humans is encoded by the PAX2 gene.

<span class="mw-page-title-main">Homeobox protein MSX-1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein MSX-1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and is responsive to thyroid hormone. MSX1 is also expressed in highly differentiated pituitary cells which until recently was thought to be expressed exclusively during embryogenesis. There is a highly conserved structural organization of the members of the MSX family of genes and their abundant expression at sites of inductive cell–cell interactions in the embryo suggest that they have a pivotal role during early development.

<span class="mw-page-title-main">EGR2</span> Protein-coding gene in the species Homo sapiens

Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene. EGR2 is a transcription regulatory factor, containing three zinc finger DNA-binding sites, and is highly expressed in a population of migrating neural crest cells. It is later expressed in the neural crest derived cells of the cranial ganglion. The protein encoded by Krox20 contains two cys2his2-type zinc fingers. Krox20 gene expression is restricted to the early hindbrain development. It is evolutionarily conserved in vertebrates, humans, mice, chicks, and zebra fish. In addition, the amino acid sequence and most aspects of the embryonic gene pattern is conserved among vertebrates, further implicating its role in hindbrain development. When the Krox20 is deleted in mice, the protein coding ability of the Krox20 gene is diminished. These mice are unable to survive after birth and exhibit major hindbrain defects. These defects include but are not limited to defects in formation of cranial sensory ganglia, partial fusion of the trigeminal nerve (V) with the facial (VII) and auditory (VII) nerves, the proximal nerve roots coming off of these ganglia were disorganized and intertwined among one another as they entered the brainstem, and there was fusion of the glossopharyngeal (IX) nerve complex.

<span class="mw-page-title-main">PAX8</span> Mammalian protein found in humans

Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.

<span class="mw-page-title-main">FOXL2</span> Transcription factor gene of the FOX family

Forkhead box protein L2 is a protein that in humans is encoded by the FOXL2 gene.

<i>TBX5</i> (gene) Protein-coding gene that affects limb development and heart and bone function

T-box transcription factor TBX5, is a protein that in humans is encoded by the TBX5 gene. Abnormalities in the TBX5 gene can result in altered limb development, Holt-Oram syndrome, Tetra-amelia syndrome, and cardiac and skeletal problems.

<span class="mw-page-title-main">PAX4</span> Protein-coding gene in humans

Paired box gene 4, also known as PAX4, is a protein which in humans is encoded by the PAX4 gene.

<span class="mw-page-title-main">HOXA13</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-A13 is a protein that in humans is encoded by the HOXA13 gene.

<span class="mw-page-title-main">AXIN2</span> Protein-coding gene in the species Homo sapiens

Axin-2, also known as axin-like protein (Axil), axis inhibition protein 2 (AXIN2), or conductin, is a protein that in humans is encoded by the AXIN2 gene.

<span class="mw-page-title-main">PITX1</span> Protein-coding gene in humans

Paired-like homeodomain 1 is a protein that in humans is encoded by the PITX1 gene.

<span class="mw-page-title-main">PAX1</span> Protein-coding gene in humans

Paired box protein Pax-1 is a protein that in humans is encoded by the PAX1 gene.

<span class="mw-page-title-main">PTF1A</span> Protein-coding gene in the species Homo sapiens

Pancreas transcription factor 1 subunit alpha is a protein that in humans is encoded by the PTF1A gene.

<span class="mw-page-title-main">Lujan–Fryns syndrome</span> Medical condition

Lujan–Fryns syndrome (LFS) is an X-linked genetic disorder that causes mild to moderate intellectual disability and features described as Marfanoid habitus, referring to a group of physical characteristics similar to those found in Marfan syndrome. These features include a tall, thin stature and long, slender limbs. LFS is also associated with psychopathology and behavioral abnormalities, and it exhibits a number of malformations affecting the brain and heart. The disorder is inherited in an X-linked dominant manner, and is attributed to a missense mutation in the MED12 gene. There is currently no treatment or therapy for the underlying MED12 malfunction, and the exact cause of the disorder remains unclear.

<span class="mw-page-title-main">Maxillary lateral incisor agenesis</span>

Maxillary lateral incisor agenesis (MLIA) is lack of development (agenesis) of one or both of the maxillary lateral incisor teeth. In normal human dentition, this would be the second tooth on either side from the center of the top row of teeth. The condition is bilateral if the incisor is absent on both sides or unilateral if only one is missing. It appears to have a genetic component.

<span class="mw-page-title-main">HES7 gene</span> Protein-coding gene in humans

(HES7) or bHLHb37 is protein coding mammalian gene found on chromosome 17 in humans. HES7 is a member of the Hairy and Enhancer of Split families of Basic helix-loop-helix proteins. The gene product is a transcription factor and is expressed cyclically in the presomitic mesoderm as part of the Notch signalling pathway. HES7 is involved in the segmentation of somites from the presomitic mesoderm in vertebrates. The HES7 gene is self-regulated by a negative feedback loop in which the gene product can bind to its own promoter. This causes the gene to be expressed in an oscillatory manner. The HES7 protein also represses expression of Lunatic Fringe (LFNG) thereby both directly and indirectly regulating the Notch signalling pathway. Mutations in HES7 can result in deformities of the spine, ribs and heart. Spondylocostal dysostosis is a common disease caused by mutations in the HES7 gene. The inheritance pattern of Spondylocostal dysostosis is autosomal recessive.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000198807 Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. 1 2 3 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. 1 2 3 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. 1 2 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. 1 2 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

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