Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors

Paul J. Newey, Michael R. Bowl, Treena Cranston, Rajesh V. Thakker

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)


The hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by the occurrence of parathyroid tumors in association with ossifying fibromas of the maxilla and/or mandible. The gene responsible for HPT-JT, known as CDC73, was identified in 2002 and encodes a 531 amino acid protein known as parafibromin. Parafibromin is predominantly a nuclear protein that interacts directly with beta-catenin and also forms part of the RNA polymerase associated factor-1 complex (Paf1C) that regulates transcription. Heterozygous germline CDC73 mutations are detected in the majority of patients with HPT-JT, and the demonstration of loss of heterozygosity (LOH) at the CDC73 locus in tumors from affected individuals is consistent with a tumor suppressor role. Somatic CDC73 mutations are a frequent finding in nonfamilial (i.e., sporadic) parathyroid carcinomas and have also been reported in benign sporadic parathyroid tumors as well as sporadic renal and fibro-osseous jaw tumors. To date, 111 independent CDC73 mutations have been identified (68 germline; 38 somatic; 5 undefined), and these occur throughout the coding region and splice sites of the CDC73 gene, with the majority (>80%) predicting premature truncation of the parafibromin protein. These CDC73 mutations, together with their clinical and biological relevance, are reviewed.

Original languageEnglish
Pages (from-to)295-307
Number of pages13
JournalHuman Mutation
Issue number3
Early online date5 Jan 2010
Publication statusPublished - Mar 2010


  • Amino Acid Sequence
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperparathyroidism/genetics
  • Mandible/pathology
  • Maxilla/pathology
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins/metabolism
  • Parathyroid Neoplasms/genetics
  • RNA Polymerase II/metabolism
  • Sequence Homology, Amino Acid
  • Syndrome
  • Tumor Suppressor Proteins/genetics
  • beta Catenin/metabolism


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