GMNN

Chr 6AD

geminin DNA replication inhibitor

Also known as: Gem, MGORS6

NCBI Gene: 51053ENSG00000112312UniProt: O75496

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]

Primary Disease Associations & Inheritance

Meier-Gorlin syndrome 6MIM #616835
AD
0
ClinVar variants
0
Pathogenic / LP
0.11
pLI score
0
Active trials
Clinical Summary— GMNN
🧬
Gene-Disease Validity (ClinGen)
Meier-Gorlin syndrome 6 · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.82LOEUF
pLI 0.115
Z-score 1.93
OE 0.32 (0.14–0.82)
Tolerant

Typical tolerance to LoF variation

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.
0.99Z-score
OE missense 0.73 (0.60–0.88)
76 obs / 104.5 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.0.32 (0.14–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.60–0.88)
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.0.85
0≤1.21.6
LoF obs/exp: 3 / 9.4Missense obs/exp: 76 / 104.5Syn Z: 0.73

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GMNN · protein map & ClinVar variants

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

Gene2Phenotype Curations

GMNN-related primordial dwarfism associated with Meier-Gorlin syndrome

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Meier-Gorlin syndrome 6

MIM #616835

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exploring the shared pathogenic mechanisms of tuberculosis and COVID-19: emphasizing the role of VNN1 in severe COVID-19.
Sun P et al.·Front Cell Infect Microbiol
2024Functional
New autoantibodies in Sjögren's disease.
Elsaghir A et al.·Curr Opin Immunol
2026Review
Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas.
Kim HE et al.·PLoS One
2012
The association of polymorphisms of CDT1 and GMNN gene with the risk of breast cancer in Chinese women: a case-control analysis.
Gao J et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2006
Suppressing SENP1 inhibits esophageal squamous carcinoma cell growth via SIRT6 SUMOylation.
Gu J et al.·Cell Oncol (Dordr)
2025
Methylation and transcriptome analyses construct a prognostic model and reveal the suppressor role of VMO1 in lung adenocarcinoma.
Wang L et al.·Cell Signal
2024Functional
Validation of Synthetic CRISPR Reagents as a Tool for Arrayed Functional Genomic Screening.
Tan J et al.·PLoS One
2016Functional
Comprehensive Analysis of the Sorafenib-Associated Druggable Targets on Differential Gene Expression and ceRNA Network in Hepatocellular Carcinoma.
Fu Z et al.·J Environ Pathol Toxicol Oncol
2023
miR-449 inhibits cell proliferation and is down-regulated in gastric cancer.
Bou Kheir T et al.·Mol Cancer
2011
High proliferation index, as determined by immunohistochemical expression of Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas.
Ramani P et al.·Virchows Arch
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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