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References OMIM Gene GeneReviews HGMD HGNC
last update : 24-02-2016
Symbol PDB3
Location 5q35.3
HGNC id 16032
Name Paget bone disease 3
Corresponding gene SQSTM1
Main clinical features
  • bone pain, deformities, pathological fracture, an increased incidence of osteosarcomas and abnormal large, multinucleated osteoclasts with paramyxovirus-like nuclear inclusions
  • chronic bone disease characterized by focal regions of increased bone resorption accompanied by increased formation of new, highly disorganized bone
  • Genetic determination autosomal dominant
    Prevalence up to 30 p100 of Paget disease
    Function/system disorder osteo-articular
    Type disease
    Gene product
    Name sequestosome 1
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/loss of function disrupting the ubiquitin-binding function, which could result in abnormal activation of the NF-kappaB pathway and the subsequent activation of the osteoclasts
    missense     mostly frequent P392L, affecting the ubiquitin-associated (UBA) domain
    Remark(s) . causing mutations identified, all of which cluster in and around the C-terminal ubiquitin-associated (UBA) domain; most common mutation identified thus far results in heterozygous substitution of a proline residue at codon 392 with a leucine (P392L), and is found in around one-quarter of PDB3 cases examined (PMID: 20971078))
  • mutated SQSTM1 accumulates in aggregates as the misfolded target of selective degradation as well as being a facilitator of the degradation process itself (PMID: 20971078))