CDC73 (cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae))
2008-02-01 Leslie Farber , Bin Tean Teh AffiliationLaboratory of Cancer Genetics, Van Andel Research Institute, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USA
Identity
HGNC
LOCATION
1q31.2
LOCUSID
ALIAS
C1orf28,FIHP,HPTJT,HRPT1,HRPT2,HYX
FUSION GENES
DNA/RNA
Description
17 exons (all coding)
Transcription
CDC73 encodes a 2.7 kb mRNA with a 1596 bp ORF. The transcript has been detected in all tissues tested to date.
Proteins
Description
531-amino acid protein (64 kD); termed parafibromin.
Expression
Ubiquitously expressed
Localisation
Nuclear, bipartite nuclear localization signal
Function
CDC73 is a tumor suppressor gene encoding a protein called parafibromin. Parafibromin is a member of the human RNA polymerase II-associated complex, Paf1. The human Paf1 complex is composed of parafibromin, LEO1, PAF1, and CTR9. Parafibromins interaction with this complex is dependent on its C-terminal domain, which is deleted in ca. 80% of clinically relevant mutations.
Homology
Parafibromin shares 54% identity and 67% similarity with the D. melanogaster ortholog and 25% identity and 45% similarity with the C. elegans ortholog. There were no homologies to known protein domains, but moderate identity (32%) and similarity (54%) to the S. cerevisiae ortholog, Cdc73.
Mutations
Germinal
Various types of mutations often leading to inactivation of protein
Somatic
Various somatic inactivating mutations found in sporadic parathyroid carcinoma
Implicated in
Entity name
Disease
HPT-JT is an autosomal dominant, multiple neoplasia syndrome.
Oncogenesis
HPT-JT syndrome is primarily characterized by hyperparathyroidism due to parathyroid tumors. Thirty percent of individuals with HPT-JT also develop ossifying fibromas, primarily of the mandible and maxilla, which are distinct from the brown tumors associated with severe hyperparathyroidism. Kidney lesions also occur in HPT-JT as bilateral cysts, renal hamartomas or Wilms tumors.
Entity name
Familial isolated hyperthyroidism
Disease
Familial isolated primary hyperparathyroidism is an autosomal dominant disorder that can represent an early stage of either the multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT) syndromes; or alternatively caused by a distinct entity involving another locus.
Entity name
Sporadic parathyroid carcinoma
Disease
These cancers characteristically result in more profound clinical manifestations of hyperparathyroidism than do parathyroid adenomas. Parathyroid carcinomas cause hyperparathyroidism. The hyperparathyroidism is usually severe, with high serum calcium level, severe bone disease, and renal stones.
Prognosis
5-years survival rate is between 50% and 70%.
Oncogenesis
Loss of parafibromin expression strongly predicts parathyroid malignancy
Entity name
Sporadic Renal Tumors
Cytogenetics
Loss of heterozygosity (LOH) of HRPT2 was found in clear cell , papillary, chromophobe renal cell carcinomas, oncocytomas, and Wilms tumors. In addition, two novel HRPT2 point mutations were detected in clear cell carcinoma and Wilms tumor.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12434154 | 2002 | HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. | Carpten JD et al |
| 15070940 | 2004 | Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene. | Cavaco BM et al |
| 17639062 | 2007 | Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation. | Cetani F et al |
| 17923126 | 2007 | Nucleolar localization of parafibromin is mediated by three nucleolar localization signals. | Hahn MA et al |
| 15492263 | 2004 | Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype. | Haven CJ et al |
| 12960210 | 2003 | HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. | Howell VM et al |
| 17639063 | 2007 | Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification. | Juhlin CC et al |
| 17314275 | 2007 | Nuclear localization of the parafibromin tumor suppressor protein implicated in the hyperparathyroidism-jaw tumor syndrome enhances its proapoptotic function. | Lin L et al |
| 18006835 | 2007 | Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior. | Liontos M et al |
| 16817812 | 2006 | Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome. | Mizusawa N et al |
| 16630820 | 2006 | Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo. | Mosimann C et al |
| 15632063 | 2005 | The parafibromin tumor suppressor protein is part of a human Paf1 complex. | Rozenblatt-Rosen O et al |
| 14585940 | 2003 | Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. | Shattuck TM et al |
| 14715834 | 2004 | Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. | Simonds WF et al |
| 16001331 | 2005 | HRPT2, a tumor suppressor gene for hyperparathyroidism-jaw tumor syndrome. | Wang PF et al |
| 15580289 | 2005 | Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. | Woodard GE et al |
| 15923622 | 2005 | The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. | Yart A et al |
| 16989776 | 2006 | Parafibromin inhibits cancer cell growth and causes G1 phase arrest. | Zhang C et al |
| 17130827 | 2007 | Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene. | Zhao J et al |
Other Information
Locus ID:
NCBI: 79577
MIM: 607393
HGNC: 16783
Ensembl: ENSG00000134371
Variants:
dbSNP: 79577
ClinVar: 79577
TCGA: ENSG00000134371
COSMIC: CDC73
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37855385 | 2024 | Targeting UBR5 inhibits postsurgical breast cancer lung metastases by inducing CDC73 and p53 mediated apoptosis. | 2 |
| 37855385 | 2024 | Targeting UBR5 inhibits postsurgical breast cancer lung metastases by inducing CDC73 and p53 mediated apoptosis. | 2 |
| 36255176 | 2023 | The clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis. | 2 |
| 36739170 | 2023 | Para This, Fibromin That: The Role of CDC73 in Parathyroid Tumors and Familial Tumor Syndromes. | 1 |
| 36255176 | 2023 | The clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis. | 2 |
| 36739170 | 2023 | Para This, Fibromin That: The Role of CDC73 in Parathyroid Tumors and Familial Tumor Syndromes. | 1 |
| 34729685 | 2022 | A novel long-range deletion spanning CDC73 and upper-stream genes discovered in a kindred of familial primary hyperparathyroidism. | 2 |
| 36177768 | 2022 | Heterozygous CDC73 mutation causing hyperparathyroidism in children and adolescents: a report of 2 cases. | 1 |
| 34729685 | 2022 | A novel long-range deletion spanning CDC73 and upper-stream genes discovered in a kindred of familial primary hyperparathyroidism. | 2 |
| 36177768 | 2022 | Heterozygous CDC73 mutation causing hyperparathyroidism in children and adolescents: a report of 2 cases. | 1 |
| 34424918 | 2021 | Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex. | 1 |
| 34424918 | 2021 | Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex. | 1 |
| 31595586 | 2020 | Tumor predisposition in an individual with chromosomal rearrangements of 1q31.2-q41 encompassing cell division cycle protein 73. | 1 |
| 32780442 | 2020 | The Oncosuppressors MEN1 and CDC73 Are Involved in lncRNA Deregulation in Human Parathyroid Tumors. | 6 |
| 31595586 | 2020 | Tumor predisposition in an individual with chromosomal rearrangements of 1q31.2-q41 encompassing cell division cycle protein 73. | 1 |
Citation
Leslie Farber ; Bin Tean Teh
CDC73 (cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae))
Atlas Genet Cytogenet Oncol Haematol. 2008-02-01
Online version: http://atlasgeneticsoncology.org/gene/181
