CDC45

Chr 22AR

cell division cycle 45

Also known as: CDC45L, CDC45L2, MGORS7, PORC-PI-1

NCBI Gene: 8318ENSG00000093009UniProt: O75419OMIM: 603465

The CDC45 protein is a core component of the CMG helicase complex that unwinds template DNA during chromosomal DNA replication initiation. Mutations cause Meier-Gorlin syndrome 7, an autosomal recessive disorder characterized by primordial dwarfism, microcephaly, and ear anomalies. The gene is highly constrained against loss-of-function variation (pLI near 1, LOEUF 0.598), reflecting its essential role in DNA replication.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.601 OMIM phenotype
Clinical Summary— CDC45
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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
24 unique Pathogenic / Likely Pathogenic· 67 VUS of 199 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
0.83Z-score
OE missense 0.88 (0.80–0.96)
315 obs / 359.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.25–0.60)
0≤0.351.4
Missense OE0.88 (0.80–0.96)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 14 / 36.6Missense obs/exp: 315 / 359.2Syn Z: 0.73

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS67
Likely Benign58
Benign28
Conflicting3
22
Pathogenic
2
Likely Pathogenic
67
VUS
58
Likely Benign
28
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
20
0
22
Likely Pathogenic
1
0
1
0
2
VUS
1
60
6
0
67
Likely Benign
0
3
30
25
58
Benign
0
0
27
1
28
Conflicting
—3
Total4638426180

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Prognostic implications of cell division cycle protein 45 expression in hepatocellular carcinoma
Yang C et al.·PeerJ
2021
Elevated CDC45 Expression Predicts Poorer Overall Survival Prognoses and Worse Immune Responses for Kidney Renal Clear Cell Carcinoma via Single-Cell and Bulk RNA-Sequencing
Zhang X et al.·Biochem Genet
2023
Deciphering the molecular functionality of Cdc45 in replisomal complex
Radhakrishnan A et al.·Biochem Biophys Rep
2024Functional
Expression of Cell Division Cycle Protein 45 in Tissue Microarrays and the CDC45 Gene by Bioinformatics Analysis in Human Hepatocellular Carcinoma and Patient Outcomes
Lu HP et al.·Med Sci Monit
2021
Correction: DNA replication protein Cdc45 directly interacts with PCNA via its PIP box in Leishmania donovani and the Cdc45 PIP box is essential for cell survival
Yadav A et al.·PLoS Pathog
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search 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
2025Open Access
Sld3CBD-Cdc45 structural insights into Cdc45 recruitment for CMG complex formation during DNA replication.
Li H et al.·Elife
2025Open 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)
2025Open 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
2024Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients