CDT1
chromatin licensing and DNA replication factor 1
Basic information
Region (hg38): 16:88803789-88809258
Links
Phenotypes
GenCC
Source:
- Meier-Gorlin syndrome 4 (Definitive), mode of inheritance: AR
- Meier-Gorlin syndrome 4 (Strong), mode of inheritance: AR
- Meier-Gorlin syndrome (Supportive), mode of inheritance: AD
- Meier-Gorlin syndrome 4 (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Meier-Gorlin syndrome 4 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Endocrine; Musculoskeletal; Neurologic | 11477602; 11992493; 21358631 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (368 variants)
- Inborn_genetic_diseases (147 variants)
- not_specified (38 variants)
- Meier-Gorlin_syndrome_4 (24 variants)
- CDT1-related_disorder (17 variants)
- Meier-Gorlin_syndrome (1 variants)
- Adenine_phosphoribosyltransferase_deficiency (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030928.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 101 | 111 | ||||
| missense | 220 | 22 | 256 | |||
| nonsense | 8 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 14 | 7 | 222 | 123 | 17 |
Highest pathogenic variant AF is 0.000113476
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CDT1 | protein_coding | protein_coding | ENST00000301019 | 10 | 6046 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.58e-10 | 0.269 | 125422 | 0 | 65 | 125487 | 0.000259 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -1.90 | 435 | 337 | 1.29 | 0.0000245 | 3425 |
| Missense in Polyphen | 86 | 78.592 | 1.0943 | 799 | ||
| Synonymous | -2.81 | 190 | 147 | 1.30 | 0.0000105 | 1190 |
| Loss of Function | 0.806 | 17 | 21.0 | 0.810 | 0.00000109 | 229 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000730 | 0.000643 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000165 | 0.000163 |
| Finnish | 0.000509 | 0.000508 |
| European (Non-Finnish) | 0.000211 | 0.000203 |
| Middle Eastern | 0.000165 | 0.000163 |
| South Asian | 0.000689 | 0.000490 |
| Other | 0.000165 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Required for both DNA replication and mitosis (PubMed:11125146, PubMed:22581055, PubMed:21856198, PubMed:14993212, PubMed:26842564). DNA replication licensing factor, required for pre-replication complex assembly. Cooperates with CDC6 and the origin recognition complex (ORC) during G1 phase of the cell cycle to promote the loading of the mini-chromosome maintenance (MCM) complex onto DNA to generate pre-replication complexes (pre-RC)(PubMed:14672932). Required also for mitosis by promoting stable kinetochore-microtubule attachments (PubMed:22581055). Potential oncogene (By similarity). {ECO:0000250|UniProtKB:Q8R4E9, ECO:0000269|PubMed:11125146, ECO:0000269|PubMed:14672932, ECO:0000269|PubMed:14993212, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22581055, ECO:0000269|PubMed:26842564}.;
- Disease
- DISEASE: Meier-Gorlin syndrome 4 (MGORS4) [MIM:613804]: A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. {ECO:0000269|PubMed:21358631, ECO:0000269|PubMed:21358632}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Mitotic G1-G1-S phases;Retinoblastoma (RB) in Cancer;DNA Replication;cdk regulation of dna replication;Activation of E2F1 target genes at G1/S;G1/S-Specific Transcription;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;Orc1 removal from chromatin;DNA Replication;Switching of origins to a post-replicative state;Synthesis of DNA;S Phase;G1/S Transition;CDT1 association with the CDC6:ORC:origin complex;Assembly of the pre-replicative complex;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic
(Consensus)
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- loftool
- 0.757
- rvis_EVS
- 1.18
- rvis_percentile_EVS
- 92.84
Haploinsufficiency Scores
- pHI
- 0.970
- hipred
- Y
- hipred_score
- 0.609
- ghis
- 0.569
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cdt1
- Phenotype
- normal phenotype;
Zebrafish Information Network
- Gene name
- cdt1
- Affected structure
- cell
- Phenotype tag
- abnormal
- Phenotype quality
- increased size
Gene ontology
- Biological process
- DNA replication checkpoint;G1/S transition of mitotic cell cycle;regulation of transcription involved in G1/S transition of mitotic cell cycle;mitotic cell cycle;mitotic cytokinesis;DNA replication;chromosome segregation;regulation of DNA-dependent DNA replication initiation;positive regulation of protein complex assembly;regulation of chromosome organization;regulation of nuclear cell cycle DNA replication;positive regulation of chromatin binding;positive regulation of DNA replication;cell division;attachment of mitotic spindle microtubules to kinetochore;kinetochore organization;DNA replication preinitiation complex assembly;response to sorbitol;deactivation of mitotic spindle assembly checkpoint;regulation of DNA replication origin binding;negative regulation of protein localization to kinetochore;positive regulation of protein localization to kinetochore;positive regulation of DNA-dependent DNA replication;positive regulation of mediator complex assembly
- Cellular component
- kinetochore;condensed chromosome kinetochore;nucleus;nucleoplasm;cytosol;nuclear body
- Molecular function
- DNA binding;chromatin binding;protein binding;DNA polymerase binding