CDC45

cell division cycle 45, the group of CMG helicase complex

Basic information

Region (hg38): 22:19479456-19520612

Previous symbols: [ "CDC45L2", "CDC45L" ]

Links

ENSG00000093009 ∙ NCBI:8318 ∙ OMIM:603465 ∙ HGNC:1739 ∙ Uniprot:O75419 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meier-Gorlin syndrome 7 (Strong), mode of inheritance: AR
• Meier-Gorlin syndrome 7 (Strong), mode of inheritance: AR
• Meier-Gorlin syndrome (Supportive), mode of inheritance: AD
• Meier-Gorlin syndrome 7 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meier-Gorlin syndrome 7	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; Musculoskeletal; Neurologic	27374770

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDC45 gene.

• not provided (234 variants)
• Inborn genetic diseases (26 variants)
• Meier-Gorlin syndrome 7 (14 variants)
• Androgen resistance syndrome (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDC45 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			3	33	6	42
missense		4	74	6	1	85
nonsense			1			1
start loss			1			1
frameshift	7					7
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region		1	6	12	2	21
non coding		1	7	52	29	89
Total	7	6	86	91	36

Highest pathogenic variant AF is 0.00000657

Variants in CDC45

This is a list of pathogenic ClinVar variants found in the CDC45 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-19479706-T-G			Likely benign (Apr 20, 2019)
22-19479774-C-G			Benign (Nov 10, 2018)
22-19479837-G-A			Likely benign (Mar 31, 2019)
22-19479939-G-T			Benign (Oct 31, 2018)
22-19479969-A-C			Uncertain significance (Nov 28, 2022)
22-19479972-T-A			Uncertain significance (Jul 12, 2022)
22-19479980-C-A			Uncertain significance (Jun 01, 2021)
22-19479987-C-G			Conflicting classifications of pathogenicity (Jan 08, 2024)
22-19479992-A-G			Likely benign (Jun 24, 2022)
22-19480009-T-C		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
22-19480024-C-T			Uncertain significance (May 04, 2022)
22-19480027-C-T			Likely benign (Apr 25, 2021)
22-19480030-G-A			Likely benign (Aug 23, 2022)
22-19480129-T-C			Benign (Oct 16, 2018)
22-19480146-C-T			Likely benign (Jun 05, 2023)
22-19480152-C-T			Likely benign (Sep 08, 2020)
22-19480153-G-T			Likely benign (Sep 03, 2021)
22-19480156-A-G			Likely pathogenic (Mar 18, 2022)
22-19480194-C-T			Benign (Jan 29, 2024)
22-19480364-G-A			Likely benign (Dec 01, 2018)
22-19480414-G-A			Benign (Mar 01, 2020)
22-19480495-AG-A			Likely benign (Aug 05, 2019)
22-19480848-C-T			Likely benign (Mar 16, 2019)
22-19480940-ACT-A			Likely benign (Mar 29, 2023)
22-19480944-T-C			Uncertain significance (Apr 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDC45	protein_coding	protein_coding	ENST00000437685	19	41154

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000462	1.00	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.828	315	359	0.877	0.0000210	3991
Missense in Polyphen		67	94.977	0.70544		1014
Synonymous	0.729	129	140	0.922	0.00000846	1091
Loss of Function	3.46	14	36.6	0.383	0.00000173	410

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.000763	0.000761
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000763	0.000761
South Asian	0.000261	0.000261
Other	0.000339	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for initiation of chromosomal DNA replication.
• Pathway: Cell cycle - Homo sapiens (human);Cell Cycle;Mitotic G1-G1-S phases;Retinoblastoma (RB) in Cancer;G1 to S cell cycle control;DNA Replication;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Activation of E2F1 target genes at G1/S;G1/S-Specific Transcription;Activation of the pre-replicative complex;Unwinding of DNA;Mitotic G1-G1/S phases;DNA Replication;DNA strand elongation;Synthesis of DNA;S Phase;G1/S Transition;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.236

Intolerance Scores

• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.82

Haploinsufficiency Scores

• pHI: 0.986
• hipred: Y
• hipred_score: 0.800
• ghis: 0.649

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdc45
• Phenotype: embryo phenotype; normal 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); cellular phenotype

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;double-strand break repair via break-induced replication;DNA replication;DNA replication initiation;regulation of chromatin silencing at telomere;DNA duplex unwinding;positive regulation of G1/S transition of mitotic cell cycle;mitotic DNA replication preinitiation complex assembly
• Cellular component: nucleus;nucleoplasm;nuclear pre-replicative complex;cytoplasm;centrosome;DNA replication preinitiation complex;replication fork protection complex
• Molecular function: chromatin binding;DNA replication origin binding;single-stranded DNA binding;protein binding;3'-5' DNA helicase activity