GMNN

Chr 6

geminin DNA replication inhibitor

Also known as: Gem, MGORS6

NCBI Gene: 51053 ENSG00000112312 UniProt: O75496

The protein geminin inhibits DNA replication by preventing incorporation of the MCM complex into pre-replication complexes and is degraded during mitosis to permit replication in the next cell cycle. Mutations in this gene cause Meier-Gorlin syndrome, a primordial dwarfism disorder characterized by severe growth restriction, microtia, absent or small patellae, and additional skeletal anomalies, inherited in an autosomal recessive pattern. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.825), consistent with the recessive inheritance pattern observed in affected individuals.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that plays a critical role in cell cycle regulation. The encoded protein inhibits DNA replication by binding to DNA replication factor Cdt1, preventing the incorporation of minichromosome maintenance proteins into the pre-replication complex. The encoded protein is expressed during the S and G2 phases of the cell cycle and is degraded by the anaphase-promoting complex during the metaphase-anaphase transition. Increased expression of this gene may play a role in several malignancies including colon, rectal and breast cancer. Alternatively spliced transcript variants have been observed for this gene, and two pseudogenes of this gene are located on the short arm of chromosome 16. [provided by RefSeq, Oct 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMeier-Gorlin syndrome 6

Clinical highlights

Gene-disease validity (ClinGen)

Meier-Gorlin syndrome 6 · ADModerateconsider for supplementary testing

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.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

0.82

LOEUF

GOF*

Mechanism· G2P

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