CDC6

cell division cycle 6

Basic information

Region (hg38): 17:40287879-40304657

Previous symbols: [ "CDC18L" ]

Links

ENSG00000094804 ∙ NCBI:990 ∙ OMIM:602627 ∙ HGNC:1744 ∙ Uniprot:Q99741 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meier-Gorlin syndrome 5 (Definitive), mode of inheritance: AR
• Meier-Gorlin syndrome (Supportive), mode of inheritance: AD
• Meier-Gorlin syndrome 5 (Limited), mode of inheritance: AR
• Meier-Gorlin syndrome 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meier-Gorlin syndrome 5	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; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	11477602; 21358632; 22333897

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDC6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDC6 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	28	2	32
missense			86	1	3	90
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			6	4	3	13
non coding			11	21	3	35
Total	0	0	104	50	8

Variants in CDC6

This is a list of pathogenic ClinVar variants found in the CDC6 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-40288068-T-G		Meier-Gorlin syndrome 5	Uncertain significance (Jan 13, 2018)
17-40288098-G-C		Meier-Gorlin syndrome 5	Uncertain significance (Jan 12, 2018)
17-40289426-T-C			Likely benign (Jan 10, 2024)
17-40289430-A-G			Uncertain significance (Sep 21, 2021)
17-40289446-A-G			Uncertain significance (Oct 07, 2022)
17-40289476-T-C			Uncertain significance (Dec 08, 2021)
17-40289481-C-T		not specified	Uncertain significance (Sep 30, 2021)
17-40289482-G-A		not specified	Uncertain significance (Jan 09, 2024)
17-40289491-A-G			Uncertain significance (Jun 22, 2020)
17-40289492-C-T			Likely benign (Jun 17, 2020)
17-40289494-A-C			Uncertain significance (Aug 19, 2022)
17-40289513-T-A			Uncertain significance (Jun 18, 2023)
17-40289534-T-C			Likely benign (Aug 03, 2022)
17-40289534-T-G		not specified	Uncertain significance (Jan 04, 2024)
17-40289543-C-T			Likely benign (Jun 01, 2023)
17-40289549-C-T		Meier-Gorlin syndrome 5	Uncertain significance (Jan 12, 2018)
17-40289548-C-CCTGTTCTCCT			Uncertain significance (Jul 26, 2022)
17-40289553-TCTC-T		Meier-Gorlin syndrome	Uncertain significance (Jun 08, 2023)
17-40289560-G-A			Uncertain significance (Jun 01, 2021)
17-40289561-T-G			Likely benign (Mar 02, 2022)
17-40289568-G-A		not specified	Uncertain significance (Mar 01, 2024)
17-40289568-G-C			Uncertain significance (Mar 01, 2018)
17-40289575-C-T			Uncertain significance (Mar 20, 2021)
17-40289581-G-A			Uncertain significance (Aug 28, 2023)
17-40289585-C-T		Meier-Gorlin syndrome 5 • not specified	Benign/Likely benign (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDC6	protein_coding	protein_coding	ENST00000209728	11	15287

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-9	0.774	125674	0	74	125748	0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.606	255	284	0.899	0.0000145	3645
Missense in Polyphen		66	87.84	0.75137		1125
Synonymous	0.542	96	103	0.932	0.00000492	1104
Loss of Function	1.54	18	26.6	0.677	0.00000140	341

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000449	0.000448
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000369	0.000369
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
• Disease: DISEASE: Meier-Gorlin syndrome 5 (MGORS5) [MIM:613805]: 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:21358632}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);Cell Cycle;Mitotic G1-G1-S phases;DNA Replication;cdk regulation of dna replication;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Transcription of E2F targets under negative control by DREAM complex;G0 and Early G1;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;CDC6 association with the ORC:origin complex;CDT1 association with the CDC6:ORC:origin complex;Assembly of the pre-replicative complex;DNA Replication Pre-Initiation;M/G1 Transition;CDK-mediated phosphorylation and removal of Cdc6;Cell Cycle;Cell Cycle, Mitotic;ATR signaling pathway;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.769
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.44

Haploinsufficiency Scores

• pHI: 0.997
• hipred: Y
• hipred_score: 0.624
• ghis: 0.592

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.404

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cdc6

Gene ontology

• Biological process: DNA replication checkpoint;regulation of cyclin-dependent protein serine/threonine kinase activity;G1/S transition of mitotic cell cycle;regulation of transcription involved in G1/S transition of mitotic cell cycle;mitotic cell cycle;DNA replication;DNA replication initiation;traversing start control point of mitotic cell cycle;negative regulation of DNA replication;negative regulation of cell population proliferation;regulation of mitotic metaphase/anaphase transition;positive regulation of cytokinesis;mitotic DNA replication checkpoint;positive regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of fibroblast proliferation;cell division;positive regulation of chromosome segregation;cellular response to vasopressin;cellular response to angiotensin
• Cellular component: spindle pole;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;spindle midzone
• Molecular function: nucleotide binding;DNA replication origin binding;protein binding;ATP binding;kinase binding