PAX9 (Paired box gene 9)

2005-08-01 Ewan Robson , Jess Whall , Michael Eccles Affiliation

Developmental Genetics Group, Department of Pathology, University of Otago, PO Box 913,Dunedin 9015, New Zealand

Identity

HGNC

PAX9

LOCATION

14q13.3

LOCUSID

5083

ALIAS

STHAG3

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

4 exons

Transcription

3 alternative splicing isoforms

Pseudogene

Proteins

Description

341 amino acids; 36.3 kDa

Expression

PAX9 is expressed in developing somites, specifically in the posterior ventrolateral region. These cells undergo an epithelial-mesenchymal transition, gaining increased motile capability as a consequence. Subsequent migration of this population generates the lateral sclerotome, which in turn gives rise to the ribs and neural arches. PAX9 contains a DNA binding paired domain, an octapeptide region and a carboxyl-terminal transactivation domain.

Localisation

Nuclear.

Function

PAX9 is a transcription factor that regulates the expression of genes involved in mediating cell proliferation, resistance to apoptosis, and cell migration. Mice homozygous for Pax9 mutations die shortly after birth, lacking the thymus, parathyroid glands and ultimobranchial bodies derived from the third and fourth pharangeal pouches, presenting aberrant head and visceral skeleton development and a complete absence of teeth.

Homology

PAX9 shares homology through the conserved paired box domain with the other members of the nine strong PAX gene family.

Mutations

Germinal

PAX9 mutations are associated with oligodontia.

Implicated in

Entity name

Oligodontia

Disease

Caused by missense and frameshift PAX9 mutations. Patients present normal primary dentition but lack most permanent molars.

Entity name

Jarcho-Levin syndrome

Disease

In humans, a reduction in expression levels of Pax9, together with those of the related Pax1 gene, have been reported in vertebral column chondrocytes of autopsied foeti presenting Jarcho-Levin syndrome, a segmentation anomaly affecting thoracic and vertebral skeletal development. This syndrome shares similarities with the phenotype of the Pax9/Pax1 double mutant mouse.

Entity name

Oesophageal invasive carcinoma and epithelial dysplasia.

Disease

PAX9 expression levels are significantly reduced in oesophageal invasive carcinoma and epithelial dysplasias compared to levels in normal tissue. There is a correlation between decreasing PAX9 expression and increased malignancy of the cancer.

Prognosis

Elevated PAX9 expression may be a useful prognostic marker indicative of favourable outcome in patients presenting oesophageal invasive carcinoma.

Bibliography

Pubmed ID	Last Year	Title	Authors
12833407	2003	Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review.	Bannykh SI et al
9297966	1997	Pax genes and organogenesis.	Dahl E et al
11941488	2002	Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia.	Das P et al
12115874	2002	Progressive loss of PAX9 expression correlates with increasing malignancy of dysplastic and cancerous epithelium of the human oesophagus.	Gerber JK et al
15615874	2005	Novel mutation of the initiation codon of PAX9 causes oligodontia.	Klein ML et al
14571272	2003	A missense mutation in PAX9 in a family with distinct phenotype of oligodontia.	Lammi L et al
9732271	1998	Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities.	Peters H et al
10556064	1999	Pax1 and Pax9 synergistically regulate vertebral column development.	Peters H et al
12490554	2003	Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome.	Rodrigo I et al
10615120	2000	Mutation of PAX9 is associated with oligodontia.	Stockton DW et al
1672661	1991	The paired box encodes a second DNA-binding domain in the paired homeo domain protein.	Treisman J et al

Other Information

Locus ID:

NCBI: 5083
MIM: 167416
HGNC: 8623
Ensembl: ENSG00000198807

Variants:

dbSNP: 5083
ClinVar: 5083
TCGA: ENSG00000198807
COSMIC: PAX9

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000198807	ENST00000361487	P55771
ENSG00000198807	ENST00000361487	Q2L4T1
ENSG00000198807	ENST00000402703	P55771
ENSG00000198807	ENST00000402703	Q2L4T1

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
18519826	2008	Molecular genetics of successful smoking cessation: convergent genome-wide association study results.	130
12657635	2003	Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9.	33
21626677	2011	Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes.	33
12490878	2002	Concomitant occurrence of canine malposition and tooth agenesis: evidence of orofacial genetic fields.	25
11941488	2002	Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia.	24
19279207	2009	Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer.	24
18978678	2008	Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts.	21
19453261	2009	High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.	20
15615874	2005	Novel mutation of the initiation codon of PAX9 causes oligodontia.	19
20634891	2010	Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.	18

Citation

Ewan Robson ; Jess Whall ; Michael Eccles

PAX9 (Paired box gene 9)

Atlas Genet Cytogenet Oncol Haematol. 2005-08-01

Online version: http://atlasgeneticsoncology.org/gene/41644/pax9