CDC45

Chr 22

cell division cycle 45

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

NCBI Gene: 8318 ENSG00000093009 UniProt: O75419

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.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6/Cdc18, the minichromosome maintenance proteins (MCMs) and DNA polymerase, which is important for early steps of DNA replication in eukaryotes. This protein has been shown to interact with MCM7 and DNA polymerase alpha. Studies of the similar gene in Xenopus suggested that this protein play a pivotal role in the loading of DNA polymerase alpha onto chromatin. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMeier-Gorlin syndrome 7

Clinical highlights

Gene-disease validity (ClinGen)

Meier-Gorlin syndrome 7 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.60

LOEUF

LOF

Mechanism· G2P

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