PAX3 Gene: Paired Box 3 Transcription Factor
Key regulator in embryonic development, associated with Waardenburg syndrome and alveolar rhabdomyosarcoma
Gene Information Card
| Symbol | PAX3 |
|---|---|
| Full Name | Paired Box 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q36.1 |
| NCBI Gene ID | 5077 ncbi.nlm.nih.gov/gene/5077 |
| Ensembl ID | ENSG00000135903 |
| UniProt ID | P23760 |
| OMIM ID | 606597 |
| HGNC ID | 8617 |
| Aliases | CDHS, HUP2, WS1, WS3, PAX-3, paired box gene 3 |
Description
PAX3 encodes a member of the paired box (PAX) family of transcription factors, characterized by a paired box DNA-binding domain. This protein plays a critical role in embryonic development, particularly in neural crest cell migration, myogenesis, and the formation of the skeletal muscle, nervous system, and melanocytes. PAX3 acts as a transcriptional regulator, binding to specific DNA sequences to control the expression of target genes. Mutations in PAX3 are associated with Waardenburg syndrome types 1 and 3, and chromosomal translocations involving PAX3 (e.g., t(2;13)(q36;q14) generating PAX3-FOXO1 fusion) are recurrent in alveolar rhabdomyosarcoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Waardenburg syndrome type 1 | Loss-of-function mutations in PAX3 disrupt neural crest cell development, leading to pigmentation defects, hearing loss, and dystopia canthorum. | ClinVar, OMIM |
| Waardenburg syndrome type 3 | Similar to type 1 but with additional limb abnormalities; caused by specific PAX3 missense or nonsense mutations. | ClinVar, OMIM |
| Alveolar rhabdomyosarcoma | Chromosomal translocation t(2;13)(q36;q14) creates PAX3-FOXO1 fusion oncoprotein, which acts as an aberrant transcription factor driving tumorigenesis. | COSMIC, NCBI Gene |
| Craniofacial-deafness-hand syndrome | Rare condition associated with PAX3 mutations, characterized by craniofacial anomalies, sensorineural hearing loss, and hand malformations. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Heart | 6.1 | Low |
| Skin | 4.7 | Low |
| Lung | 2.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RH30 (alveolar rhabdomyosarcoma) | 15.2 | PAX3-FOXO1 fusion positive |
| RD (embryonal rhabdomyosarcoma) | 3.1 | Low expression |
| HEK293 | 1.5 | Low expression |
| SH-SY5Y (neuroblastoma) | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.649C>T (p.Arg217Ter) | Nonsense | Common in WS1 | Loss of function |
| c.667C>T (p.Arg223Trp) | Missense | Common in WS1/WS3 | Dominant negative |
| t(2;13)(q36;q14) | Translocation | Recurrent in ARMS | Gain of function (PAX3-FOXO1 fusion) |
| c.916C>T (p.Arg306Cys) | Missense | Rare in WS3 | Dominant negative |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay, observed in Waardenburg syndrome type 1.
Gain of Function (GOF)
PAX3-FOXO1 fusion resulting from t(2;13) translocation creates a potent oncogenic transcription factor with enhanced transcriptional activity.
Dominant Negative (DN)
Missense mutations in the paired domain (e.g., p.Arg223Trp) that disrupt DNA binding but retain dimerization capacity, interfering with wild-type PAX3 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • regulation of transcription by RNA polymerase II | • neural crest cell migration |
| • skeletal muscle cell differentiation | • embryonic skeletal system morphogenesis |
Pathways
• PAX3-FOXO1 signaling in alveolar rhabdomyosarcoma
• Neural crest cell differentiation
• Myogenesis
Protein Summary
PAX3 is a 479-amino acid transcription factor containing a paired box domain, a homeobox domain, and a C-terminal transactivation domain. It binds DNA as a dimer and regulates genes involved in cell proliferation, migration, and differentiation. The PAX3-FOXO1 fusion protein retains the DNA-binding domains of PAX3 but replaces the transactivation domain with the FOXO1 transactivation domain, leading to aberrant activation of target genes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAX3 Knockout HEK293 Cell Line | EDJ-KQ2686 | Human | 5077 | Details Get a Quote |
| PAX3 Knockout HeLa Cell Line | EDJ-KQ54082 | Human | 5077 | Details Get a Quote |
| PAX3 Knockout A-549 Cell Line | EDJ-KQ62570 | Human | 5077 | Details Get a Quote |
| PAX3 Knockout HCT 116 Cell Line | EDJ-KQ71040 | Human | 5077 | Details Get a Quote |
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