Paired box gene 9, also known as PAX9, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

which in humans is encoded by the ''PAX9''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. It is also found in other

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

Expression and function

This gene is a member of the paired box (PAX) family of

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s. 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 Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...

. 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 A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

elements. PAX9 plays a role in the absence of

wisdom teeth A third molar, commonly called wisdom tooth, is one of the three molars per quadrant of the human dentition. It is the most posterior of the three. The age at which wisdom teeth come through ( erupt) is variable, but this generally occurs betw ...

in some human populations (possibly along with the less well studied

AXIN2 Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a protein that in humans is encoded by the ''AXIN2'' gene. Function The Axin-related protein, Axin2, presumably plays an important role in the r ...

and

MSX1 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 ...

Clinical significance

This gene was found amplified in

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...

. The amplification covers three tissue developmental genes -

TTF1 Transcription termination factor 1 is a protein that in humans is encoded by the ''TTF1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gene ...

NKX2-8 Marine Corps Air Station Miramar (MCAS Miramar) , formerly Naval Auxiliary Air Station (NAAS) Miramar and Naval Air Station (NAS) Miramar, is a United States Marine Corps installation that is home to the 3rd Marine Aircraft Wing, which is the av ...

, 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.

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. 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 PAX9 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 PAX9 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 PAX9 gene suggests that the loss of function due to the absence DNA binding domain is a mechanism that causes oligodontia. 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.

Interactions

PAX9 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

JARID1B Lysine-specific demethylase 5B also known as histone demethylase JARID1B is a demethylase enzyme that in humans is encoded by the ''KDM5B'' gene. JARID1B belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily. Function Jarid1B (a ...

References

External links