CDC73
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CDC73 (HGNC:16783) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
cell division cycle 73
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
C1orf28, HRPT2, HRPT1
Alias symbols
parafibromin, FIHP
%HI
11.74(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.42(Read more about gnomAD LOEUF score)
Cytoband
1q31.2
Genomic Coordinates
GRCh37/hg19: chr1:193091161-193223945 NCBI Ensembl UCSC
GRCh38/hg38: chr1:193122031-193254815 NCBI Ensembl UCSC
MANE Select Transcript
NM_024529.5 ENST00000367435.5 (Read more about MANE Select)
Function
Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-16705
ClinGen Curation ID:
CCID:006817
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
04/13/2022

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Hyperparathyroidism with jaw tumors Monarch
HI Evidence:
  • PUBMED: 12434154
    Carpten et al., describe 24 kindreds (some previously reported) with HPT-JT syndrome, performed linkage studies and then sequencing of CDC73 (referred to as HPRT2 in the paper). In 13 kindreds a heterozygous loss of function sequence variant in CDC73 observed. 5 of these have pedigrees presented in the paper.
  • PUBMED: 28774260
    Guarnieri et al., describe a family with a heterozygous deletion of exons 4 through 10 of CDC73 in a family with HPT-JT. The proband presented with parathyroid carcinoma as well as uterine leiomyomata. Her father and daughter were known to have hyperparathyroidism and carried the variant CDC73 allele.
  • PUBMED: 21324824
    Pichardo-Lowden et al., report a family with a proband presenting with primary hyperparathyroidism from parathyroid adenoma, shown to be heterozygous for c.205dupC variant, resulting in p.Leu69Profs*13.
  • PUBMED: 27544721
    Serrano-Gonzalez et al., presents a 14 yo girl with parathyroid carcinoma and germline heterozygous c.70G>T, p.Glu24Ter in CDC73.
  • PUBMED: 32590342
    Li et al., studied individuals with germline CDC73 variation and risk of parathyroid cancer. Two cohorts studied (Discovery cohort of n=68 for individuals with inherited metabolic disease and hyperparathyroidism who received genetic testing) and literature (validation cohort n=351). Loss of function pathogenic variation were lumped together as "high-impact mutations" and assessed separately from other types ("low-impact mutations"). While both categories were associated with a similar risk of developing primary hyperparathyroidism, individuals with the high-impact mutations were 6.6x more likely to develop parathyroid carcinoma compared to the low-impact group (hazard ratio=6.60; P=0.03; 95% CI, 2.7–16).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000001.10) (NC_000001.11)