CDC73
cell division cycle 73, the group of MicroRNA protein coding host genes|Paf1/RNA polymerase II complex
Basic information
Region (hg38): 1:193121982-193254815
Previous symbols: [ "C1orf28", "HRPT2", "HRPT1" ]
Links
Phenotypes
GenCC
Source:
- familial isolated hyperparathyroidism (Supportive), mode of inheritance: AD
- parathyroid gland carcinoma (Strong), mode of inheritance: AD
- hyperparathyroidism 2 with jaw tumors (Definitive), mode of inheritance: AD
- hyperparathyroidism 2 with jaw tumors (Definitive), mode of inheritance: AD
- parathyroid gland carcinoma (Strong), mode of inheritance: AD
- hyperparathyroidism 1 (Strong), mode of inheritance: AD
- hyperparathyroidism 2 with jaw tumors (Strong), mode of inheritance: AD
- hyperparathyroidism 2 with jaw tumors (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hyperparathyroidism 1; Hyperparathyroidism 2 with jaw tumors; Carcinoma, parathyroid | AD | Endocrine; Oncologic | Parathyroidectomy (or medical treatment in individuals unable to undergo parathyroidectomy) may be necessary to normalize calcium levels, and parathyroid adenomas may recur; Surveillance and early diagnosis/treatment of specific manifestations, including jaw tumor recurrence, parathyroid carcinoma, and renal neoplasms, is indicated | Endocrine; Oncologic; Renal | 11157996; 3592449; 12434154; 14585940; 14715834; 14985403; 15531515; 15606373; 16720667; 17639062; 17666472; 21361849; 20301744; 22187299; 23652676; 23757631 |
ClinVar
This is a list of variants' phenotypes submitted to
- Parathyroid carcinoma (1103 variants)
- Hereditary cancer-predisposing syndrome (522 variants)
- Hyperparathyroidism 1 (129 variants)
- Hyperparathyroidism 2 with jaw tumors (116 variants)
- not provided (84 variants)
- not specified (33 variants)
- Inborn genetic diseases (15 variants)
- Hyperparathyroidism 1;Parathyroid carcinoma;Hyperparathyroidism 2 with jaw tumors (12 variants)
- Parathyroid carcinoma;Hyperparathyroidism 2 with jaw tumors;Hyperparathyroidism 1 (9 variants)
- Hyperparathyroidism 2 with jaw tumors;Hyperparathyroidism 1;Parathyroid carcinoma (8 variants)
- Isolated Hyperparathyroidism (8 variants)
- Parathyroid carcinoma;Hyperparathyroidism 1;Hyperparathyroidism 2 with jaw tumors (6 variants)
- Hyperparathyroidism 1;Hyperparathyroidism 2 with jaw tumors;Parathyroid carcinoma (5 variants)
- CDC73-related condition (3 variants)
- Hyperparathyroidism 2 with jaw tumors;Parathyroid carcinoma;Hyperparathyroidism 1 (3 variants)
- Familial cancer of breast (1 variants)
- Ovarian cancer (1 variants)
- Multiple endocrine neoplasia, type 1 (1 variants)
- Parathyroid adenoma, somatic (1 variants)
- Hyperparathyroidism (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDC73 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 294 | 297 | ||||
| missense | 443 | 446 | ||||
| nonsense | 32 | 36 | ||||
| start loss | 3 | |||||
| frameshift | 43 | 46 | ||||
| inframe indel | 7 | |||||
| splice donor/acceptor (+/-2bp) | 13 | 23 | ||||
| splice region ? | 1 | 43 | 85 | 1 | 130 | |
| non coding ? | 104 | 225 | 26 | 355 | ||
| Total | 85 | 22 | 559 | 521 | 26 |
Highest pathogenic variant AF is 0.00000659
Variants in CDC73
This is a list of pathogenic ClinVar variants found in the CDC73 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-193122011-G-C | Hyperparathyroidism 1 • Parathyroid carcinoma • Hyperparathyroidism 2 with jaw tumors | Uncertain significance (Jan 13, 2018) | ||
| 1-193122015-C-G | Hyperparathyroidism 2 with jaw tumors • Parathyroid carcinoma • Hyperparathyroidism 1 | Uncertain significance (Jan 13, 2018) | ||
| 1-193122034-A-G | Hyperparathyroidism 1 • Parathyroid carcinoma • Hyperparathyroidism 2 with jaw tumors | Uncertain significance (Jan 12, 2018) | ||
| 1-193122058-G-C | Parathyroid carcinoma • Hyperparathyroidism 2 with jaw tumors • Hyperparathyroidism 1 | Uncertain significance (Jan 13, 2018) | ||
| 1-193122066-C-T | Hyperparathyroidism 1 • Hyperparathyroidism 2 with jaw tumors • Parathyroid carcinoma | Uncertain significance (Jan 13, 2018) | ||
| 1-193122080-G-A | Parathyroid carcinoma • Hyperparathyroidism 1 • Hyperparathyroidism 2 with jaw tumors | Uncertain significance (Jan 12, 2018) | ||
| 1-193122106-G-A | Hyperparathyroidism 1 • Parathyroid carcinoma • Hyperparathyroidism 2 with jaw tumors | Benign/Likely benign (Jul 07, 2023) | ||
| 1-193122171-C-T | Hyperparathyroidism 2 with jaw tumors • Hyperparathyroidism 1 • Parathyroid carcinoma | Uncertain significance (Jan 13, 2018) | ||
| 1-193122172-C-T | not specified | Likely benign (Aug 15, 2023) | ||
| 1-193122189-AG-A | not specified • Hereditary cancer-predisposing syndrome | Benign/Likely benign (Aug 30, 2022) | ||
| 1-193122189-A-AG | not specified • Isolated Hyperparathyroidism • Parathyroid carcinoma • Hyperparathyroidism 2 with jaw tumors • Hereditary cancer-predisposing syndrome • CDC73-related disorder | Conflicting classifications of pathogenicity (Apr 01, 2024) | ||
| 1-193122190-G-A | Parathyroid carcinoma • Hyperparathyroidism 2 with jaw tumors • Hyperparathyroidism 1 • Hyperparathyroidism | Conflicting classifications of pathogenicity (Jul 07, 2023) | ||
| 1-193122191-G-T | not specified • Parathyroid carcinoma • Hyperparathyroidism 2 with jaw tumors • Hyperparathyroidism 1 | Benign/Likely benign (Jan 13, 2018) | ||
| 1-193122192-G-C | Uncertain significance (Apr 12, 2023) | |||
| 1-193122196-G-T | Hereditary cancer-predisposing syndrome | Uncertain significance (Jun 16, 2023) | ||
| 1-193122197-G-C | Hereditary cancer-predisposing syndrome | Uncertain significance (Feb 10, 2024) | ||
| 1-193122197-G-GA | Hereditary cancer-predisposing syndrome | Uncertain significance (Aug 24, 2022) | ||
| 1-193122198-A-G | Hereditary cancer-predisposing syndrome | Uncertain significance (Mar 08, 2023) | ||
| 1-193122199-A-G | Hereditary cancer-predisposing syndrome | Uncertain significance (Jan 13, 2022) | ||
| 1-193122200-G-T | Hereditary cancer-predisposing syndrome | Uncertain significance (Apr 08, 2022) | ||
| 1-193122201-A-G | Parathyroid carcinoma | Pathogenic (Jul 14, 2023) | ||
| 1-193122201-A-AT | Parathyroid carcinoma | Pathogenic (Dec 05, 2022) | ||
| 1-193122202-T-C | Inborn genetic diseases | Pathogenic (Mar 17, 2017) | ||
| 1-193122202-TG-T | Parathyroid carcinoma | Pathogenic (Apr 16, 2016) | ||
| 1-193122203-G-A | Hyperparathyroidism 2 with jaw tumors | Pathogenic (Dec 01, 2002) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CDC73 | protein_coding | protein_coding | ENST00000367435 | 17 | 131885 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000504 | 125715 | 0 | 6 | 125721 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.73 | 119 | 301 | 0.395 | 0.0000163 | 3456 |
| Missense in Polyphen | 25 | 90.928 | 0.27494 | 1089 | ||
| Synonymous | -0.370 | 103 | 98.3 | 1.05 | 0.00000497 | 1025 |
| Loss of Function | 5.52 | 3 | 41.2 | 0.0728 | 0.00000262 | 407 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000290 | 0.0000290 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000355 | 0.0000352 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both indepentently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors. {ECO:0000269|PubMed:15580289, ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15923622, ECO:0000269|PubMed:16630820, ECO:0000269|PubMed:16989776, ECO:0000269|PubMed:19136632, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}.;
- Disease
- DISEASE: Hyperparathyroidism 1 (HRPT1) [MIM:145000]: An autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid hyperplasia, adenomas, and carcinomas. {ECO:0000269|PubMed:12434154, ECO:0000269|PubMed:12960210, ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:16487440, ECO:0000269|PubMed:18755853}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hyperparathyroidism 2 with jaw tumors (HRPT2) [MIM:145001]: An autosomal dominant neoplasia syndrome characterized by primary hyperparathyroidism, ossifying fibroma of the maxilla and/or mandible, renal tumor, and uterine tumors. It is associated with increased risk of parathyroid cancer. {ECO:0000269|PubMed:12434154, ECO:0000269|PubMed:15613436, ECO:0000269|PubMed:16487440}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Parathyroid carcinoma (PRTC) [MIM:608266]: These cancers characteristically result in more profound clinical manifestations of hyperparathyroidism than do parathyroid adenomas, the most frequent cause of primary hyperparathyroidism. Early en bloc resection of the primary tumor is the only curative treatment. {ECO:0000269|PubMed:14585940}. Note=The gene represented in this entry is involved in disease pathogenesis.;
- Pathway
- WNT-Ncore;Endoderm Differentiation;Signaling by WNT;Signal Transduction;Gene expression (Transcription);RNA Polymerase II Pre-transcription Events;Post-translational protein modification;Formation of RNA Pol II elongation complex ;Metabolism of proteins;RNA Polymerase II Transcription;RNA Polymerase II Transcription Elongation;Hedgehog ,on, state;Signaling by Hedgehog;Protein ubiquitination;E3 ubiquitin ligases ubiquitinate target proteins;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT
(Consensus)
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- loftool
- 0.112
- rvis_EVS
- -0.38
- rvis_percentile_EVS
- 27.42
Haploinsufficiency Scores
- pHI
- 0.254
- hipred
- Y
- hipred_score
- 0.816
- ghis
- 0.678
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cdc73
- Phenotype
- endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; muscle phenotype; skeleton phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- cdc73
- Affected structure
- cardiac muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;endodermal cell fate commitment;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;mRNA polyadenylation;cell cycle;negative regulation of cell population proliferation;histone monoubiquitination;Wnt signaling pathway;protein ubiquitination;stem cell population maintenance;positive regulation of Wnt signaling pathway;positive regulation of mRNA 3'-end processing;protein destabilization;positive regulation of transcription elongation from RNA polymerase II promoter;histone H2B ubiquitination;recruitment of 3'-end processing factors to RNA polymerase II holoenzyme complex;negative regulation of myeloid cell differentiation;positive regulation of transcription by RNA polymerase II;negative regulation of fibroblast proliferation;negative regulation of epithelial cell proliferation;cellular response to lipopolysaccharide;positive regulation of cell cycle G1/S phase transition;beta-catenin-TCF complex assembly;negative regulation of G1/S transition of mitotic cell cycle
- Cellular component
- nuclear chromosome, telomeric region;nucleus;nucleoplasm;cytosol;Cdc73/Paf1 complex
- Molecular function
- RNA polymerase II complex binding;protein binding