PAX3
Chr 2ADSomaticARpaired box 3
Also known as: CDHS, HUP2, PAX-3, WS1, WS3
This transcription factor contains a paired box domain and homeodomain and regulates cell proliferation, migration, and apoptosis during neural development and myogenesis. Mutations cause Waardenburg syndrome types 1 and 3 (characterized by congenital hearing loss and pigmentary abnormalities), craniofacial-deafness-hand syndrome, and alveolar rhabdomyosarcoma through both germline and somatic mechanisms. The gene follows autosomal dominant inheritance for the syndromic conditions and autosomal recessive inheritance for some presentations.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PAX3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Spastic Myopathy in Adults With Cerebral Palsy
RECRUITINGA Clinical Study on the Efficacy and Safety of All-trans Retinoic Acid Combined With VAC Regimen in the Treatment of Intermediate-to-high-risk Rhabdomyosarcoma
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools