CDC45

Chr 22AR

cell division cycle 45

NCBI Gene: 8318ENSG00000093009UniProt: O75419

Required for initiation of chromosomal DNA replication. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built

Primary Disease Associations & Inheritance

Meier-Gorlin syndrome 7MIM #617063
AR
281
ClinVar variants
88
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CDC45
🧬
Gene-Disease Validity (ClinGen)
Meier-Gorlin syndrome 7 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
88 Pathogenic / Likely Pathogenic· 96 VUS of 281 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.60LOEUF
pLI 0.000
Z-score 3.46
OE 0.38 (0.25–0.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.83Z-score
OE missense 0.88 (0.80–0.96)
315 obs / 359.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.25–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.80–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 14 / 36.6Missense obs/exp: 315 / 359.2Syn Z: 0.73

ClinVar Variant Classifications

281 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic81
Likely Pathogenic7
VUS96
Likely Benign94
Benign2
Conflicting1
81
Pathogenic
7
Likely Pathogenic
96
VUS
94
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
77
0
81
Likely Pathogenic
4
0
2
1
7
VUS
0
86
9
1
96
Likely Benign
0
2
52
40
94
Benign
0
0
1
1
2
Conflicting
—1
Total88814143281

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CDC45 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CDC45-related Meier-Gorlin syndrome and craniosynostosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Meier-Gorlin syndrome 7

MIM #617063

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of genetic profile and biomarkers involved in acute respiratory distress syndrome.
Cao S et al.·Intensive Care Med
2024
The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs.
Jo U et al.·Mol Cancer Ther
2024
Clinical genetics of craniosynostosis.
Wilkie AOM et al.·Curr Opin Pediatr
2017Review
Further delineation of CDC45-related Meier-Gorlin syndrome with craniosynostosis and review of literature.
Ting CY et al.·Eur J Med Genet
2020Review
High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.
Fu Y et al.·Cell Prolif
2022
Validation of CDC45 as a novel biomarker for diagnosis and prognosis of gastric cancer.
Wu L et al.·PeerJ
2024
The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome.
Nielsen-Dandoroff E et al.·Eur J Hum Genet
2023Review
A comprehensive review and in silico analysis of the role of survivin (BIRC5) in hepatocellular carcinoma hallmarks: A step toward precision.
Mohamed NM et al.·Int J Biol Macromol
2025Review
Allelic bias contributes to heterogeneous phenotypes of NK cell deficiency.
Seo S et al.·Cell Rep
2025
A second hotspot for pathogenic exon-skipping variants in CDC45.
Schoch K et al.·Eur J Hum Genet
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of Cdc45-interacting partners uncovers two Leishmania donovani proteins involved in DNA replication.
Dashora V et al.·BMC Microbiol
2025🔓 Open Access
Sld3CBD-Cdc45 structural insights into Cdc45 recruitment for CMG complex formation during DNA replication.
Li H et al.·Elife
2025🔓 Open Access
Effects of CDC45 mutations on DNA replication and genome stability.
Denkiewicz-Kruk M et al.·Biochim Biophys Acta Mol Cell Res
2025
Functional Analysis and Experimental Validation of the Prognostic and Immune Effects of the Oncogenic Protein CDC45 in Breast Cancer.
Zhang JN et al.·Breast Cancer (Dove Med Press)
2025🔓 Open AccessFunctional
Itaconate Ameliorates Experimental Autoimmune Uveitis by Modulating Teff/Treg Cell Imbalance Via the DNAJA1/CDC45 Axis.
Jiang Q et al.·Invest Ophthalmol Vis Sci
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools