CDT1

chromatin licensing and DNA replication factor 1

Basic information

Region (hg38): 16:88803788-88809258

Links

ENSG00000167513 ∙ NCBI:81620 ∙ OMIM:605525 ∙ HGNC:24576 ∙ Uniprot:Q9H211 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the CDT1 gene.

• not provided (293 variants)
• not specified (47 variants)
• Inborn genetic diseases (45 variants)
• Meier-Gorlin syndrome 4 (21 variants)
• Adenine phosphoribosyltransferase deficiency (1 variants)
• Meier-Gorlin syndrome (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.

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			2	59	14	75
missense		2	148	6	13	169
nonsense	2	2				4
start loss						0
frameshift	3					3
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)		2	1			3
splice region			7	6	2	15
non coding	1		3	31	18	53
Total	7	6	155	96	45

Highest pathogenic variant AF is 0.0000591

Variants in CDT1

This is a list of pathogenic ClinVar variants found in the CDT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-88803835-G-A			Uncertain significance (Aug 09, 2022)
16-88803839-A-T			Uncertain significance (Mar 28, 2022)
16-88803841-C-T			Uncertain significance (Nov 29, 2022)
16-88803842-G-T		Inborn genetic diseases	Uncertain significance (Dec 05, 2023)
16-88803846-C-A			Benign (Jan 12, 2024)
16-88803846-CG-C			Pathogenic (Jul 14, 2022)
16-88803863-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
16-88803876-C-T			Likely benign (Mar 12, 2022)
16-88803877-G-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
16-88803887-G-A			Uncertain significance (Apr 27, 2020)
16-88803888-C-T			Likely benign (Sep 18, 2022)
16-88803889-A-C		Inborn genetic diseases	Uncertain significance (Nov 30, 2021)
16-88803889-A-G			Uncertain significance (Sep 01, 2022)
16-88803906-G-T		not specified	Benign/Likely benign (Oct 24, 2023)
16-88803921-C-G			Likely benign (Aug 28, 2021)
16-88803931-A-C			Likely benign (Jan 19, 2024)
16-88803940-C-T			Uncertain significance (May 27, 2023)
16-88803942-C-T		not specified	Benign (Jan 31, 2024)
16-88803947-C-T		Inborn genetic diseases	Uncertain significance (Nov 07, 2023)
16-88803951-G-C			Likely benign (Apr 13, 2023)
16-88803954-C-G			Likely benign (Aug 27, 2023)
16-88803954-C-T			Likely benign (Nov 10, 2022)
16-88803957-C-G			Likely benign (Feb 28, 2023)
16-88803961-A-C		not specified	Benign (Jan 24, 2024)
16-88803973-C-A			Uncertain significance (May 25, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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