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... See more...

Aliases for GMNN Gene

Aliases for GMNN Gene

  • Geminin DNA Replication Inhibitor 2 3 5
  • Geminin 3 4
  • Gem 2 3
  • MGORS6 3
  • GMNN 5

External Ids for GMNN Gene

Previous GeneCards Identifiers for GMNN Gene

  • GC06P024832
  • GC06P024883
  • GC06P024778
  • GC06P024725

Summaries for GMNN Gene

Entrez Gene Summary for GMNN Gene

  • 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]

GeneCards Summary for GMNN Gene

GMNN (Geminin DNA Replication Inhibitor) is a Protein Coding gene. Diseases associated with GMNN include Meier-Gorlin Syndrome 6 and Meier-Gorlin Syndrome 1. Among its related pathways are Cell Cycle, Mitotic and CDK-mediated phosphorylation and removal of Cdc6. Gene Ontology (GO) annotations related to this gene include transcription corepressor activity and repressing transcription factor binding. An important paralog of this gene is MCIDAS.

UniProtKB/Swiss-Prot Summary for GMNN Gene

  • Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC) (PubMed:9635433, PubMed:14993212, PubMed:20129055, PubMed:24064211). It is degraded during the mitotic phase of the cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Inhibits histone acetyltransferase activity of KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation and DNA replication licensing (PubMed:20129055). Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (PubMed:22615398).

Gene Wiki entry for GMNN Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GMNN Gene

Genomics for GMNN Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GMNN Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GMNN on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GMNN

Top Transcription factor binding sites by QIAGEN in the GMNN gene promoter:
  • AhR
  • FOXD3
  • FOXJ2
  • FOXJ2 (long isoform)
  • HNF-3beta
  • Msx-1
  • p53
  • PPAR-gamma1
  • PPAR-gamma2
  • Sox5

Genomic Locations for GMNN Gene

Latest Assembly
chr6:24,774,931-24,786,099
(GRCh38/hg38)
Size:
11,169 bases
Orientation:
Plus strand

Previous Assembly
chr6:24,775,165-24,786,327
(GRCh37/hg19 by Entrez Gene)
Size:
11,163 bases
Orientation:
Plus strand

chr6:24,775,159-24,786,327
(GRCh37/hg19 by Ensembl)
Size:
11,169 bases
Orientation:
Plus strand

Genomic View for GMNN Gene

Genes around GMNN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GMNN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GMNN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GMNN Gene

Proteins for GMNN Gene

  • Protein details for GMNN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75496-GEMI_HUMAN
    Recommended name:
    Geminin
    Protein Accession:
    O75496
    Secondary Accessions:
    • B3KMM8
    • Q9H1Z1

    Protein attributes for GMNN Gene

    Size:
    209 amino acids
    Molecular mass:
    23565 Da
    Quaternary structure:
    • Homotetramer (PubMed:15313623, PubMed:15260975, PubMed:15378034, PubMed:19906994). Interacts with CDT1; this inhibits binding of the MCM complex to origins of replication (PubMed:14993212, PubMed:21543332, PubMed:15260975, PubMed:19906994). The complex with CDT1 exists in two forms, a 'permissive' heterotrimer and an 'inhibitory' heterohexamer (PubMed:14993212, PubMed:15260975, PubMed:19906994). Interacts (via coiled-coil domain) with IDAS (via coiled-coil domain); this targets GMNN to the nucleus (PubMed:21543332). The heterodimer formed by GMNN and MCIDAS has much lower affinity for CDT1 than the GMNN homodimer (PubMed:24064211). Interacts with a subset of Hox proteins, affinity increasing from anterior to posterior types, the strongest interaction being with HOXB1, HOXC9 and HOXD10 (PubMed:22615398). Interacts with LRWD1 from G1/S to mitosis (PubMed:22645314).

    Three dimensional structures from OCA and Proteopedia for GMNN Gene

neXtProt entry for GMNN Gene

Post-translational modifications for GMNN Gene

  • Phosphorylated during mitosis. Phosphorylation at Ser-184 by CK2 results in enhanced binding to Hox proteins and more potent inhibitory effect on Hox transcriptional activity.
  • Ubiquitination at Lys50
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for GMNN Gene

Domains & Families for GMNN Gene

Gene Families for GMNN Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for GMNN Gene

Suggested Antigen Peptide Sequences for GMNN Gene

GenScript: Design optimal peptide antigens:
  • Geminin (GEMI_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O75496

UniProtKB/Swiss-Prot:

GEMI_HUMAN :
  • Belongs to the geminin family.
Family:
  • Belongs to the geminin family.
genes like me logo Genes that share domains with GMNN: view

Function for GMNN Gene

Molecular function for GMNN Gene

UniProtKB/Swiss-Prot Function:
Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC) (PubMed:9635433, PubMed:14993212, PubMed:20129055, PubMed:24064211). It is degraded during the mitotic phase of the cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Inhibits histone acetyltransferase activity of KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation and DNA replication licensing (PubMed:20129055). Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (PubMed:22615398).

Phenotypes From GWAS Catalog for GMNN Gene

Gene Ontology (GO) - Molecular Function for GMNN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IDA 11125146
GO:0003714 transcription corepressor activity IEA --
GO:0005515 protein binding IPI 11125146
GO:0042826 histone deacetylase binding IPI 16924111
GO:0070491 repressing transcription factor binding IEA --
genes like me logo Genes that share ontologies with GMNN: view
genes like me logo Genes that share phenotypes with GMNN: view

Human Phenotype Ontology for GMNN Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GMNN Gene

MGI Knock Outs for GMNN:
  • Gmnn Gmnn<tm1Nyma>
  • Gmnn Gmnn<tm1.1Kio>
  • Gmnn Gmnn<tm1.2Kio>
  • Gmnn Gmnn<tm1a(KOMP)Wtsi>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GMNN

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for GMNN Gene

Localization for GMNN Gene

Subcellular locations from UniProtKB/Swiss-Prot for GMNN Gene

Cytoplasm. Nucleus. Note=Mainly cytoplasmic but can be relocalized to the nucleus. {ECO:0000269 PubMed:21543332}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GMNN gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 2
cytoskeleton 2
plasma membrane 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GMNN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 21543332
GO:0005654 nucleoplasm IDA,TAS --
GO:0005737 cytoplasm IEA,IDA 21543332
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with GMNN: view

Pathways & Interactions for GMNN Gene

genes like me logo Genes that share pathways with GMNN: view

Pathways by source for GMNN Gene

2 GeneGo (Thomson Reuters) pathways for GMNN Gene
  • Cell cycle Start of DNA replication in early S phase
  • Cell cycle_Role of APC in cell cycle regulation
1 Cell Signaling Technology pathway for GMNN Gene

SIGNOR curated interactions for GMNN Gene

Inactivates:

Gene Ontology (GO) - Biological Process for GMNN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000082 G1/S transition of mitotic cell cycle TAS --
GO:0006275 regulation of DNA replication IEA,IMP 17234884
GO:0007049 cell cycle IEA --
GO:0008156 negative regulation of DNA replication IEA,IDA 9635433
GO:0009887 animal organ morphogenesis IEA --
genes like me logo Genes that share ontologies with GMNN: view

Drugs & Compounds for GMNN Gene

(1) Drugs for GMNN Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with GMNN: view

Transcripts for GMNN Gene

mRNA/cDNA for GMNN Gene

4 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GMNN

Alternative Splicing Database (ASD) splice patterns (SP) for GMNN Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b · 2c ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c ^ 6a · 6b ^ 7 ^ 8a · 8b · 8c · 8d · 8e
SP1: - - - - -
SP2: - - - -
SP3: - -
SP4: - - - - -
SP5: - - - - - -
SP6: -
SP7:
SP8: -

Relevant External Links for GMNN Gene

GeneLoc Exon Structure for
GMNN

Expression for GMNN Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GMNN Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GMNN Gene

This gene is overexpressed in Pancreas (x4.7).

Protein differential expression in normal tissues from HIPED for GMNN Gene

This gene is overexpressed in Fetal ovary (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GMNN Gene



Protein tissue co-expression partners for GMNN Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GMNN

SOURCE GeneReport for Unigene cluster for GMNN Gene:

Hs.234896

Evidence on tissue expression from TISSUES for GMNN Gene

  • Lung(4.4)
  • Skin(2.6)
  • Pancreas(2.5)
  • Nervous system(2.4)
  • Intestine(2.4)
  • Blood(2.4)
  • Kidney(2.3)
  • Bone marrow(2.2)
  • Lymph node(2.1)
  • Liver(2)
genes like me logo Genes that share expression patterns with GMNN: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GMNN Gene

Orthologs for GMNN Gene

This gene was present in the common ancestor of chordates.

Orthologs for GMNN Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GMNN 29 30
  • 99.36 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia GMNN 29 30
  • 86.05 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia GMNN 29 30
  • 84.37 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Gmnn 29
  • 83.9 (n)
Mouse
(Mus musculus)
Mammalia Gmnn 29 16 30
  • 83.25 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia GMNN 30
  • 59 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia GMNN 30
  • 59 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GMNN 29 30
  • 66.46 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 53 (a)
OneToMany
-- 30
  • 42 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia gmnn 29
  • 62.91 (n)
Str.6403 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.461 29
Zebrafish
(Danio rerio)
Actinopterygii gmnn 29 30
  • 56.46 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.5193 30
  • 20 (a)
OneToOne
Species where no ortholog for GMNN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for GMNN Gene

ENSEMBL:
Gene Tree for GMNN (if available)
TreeFam:
Gene Tree for GMNN (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GMNN: view image
Alliance of Genome Resources:
Additional Orthologs for GMNN

Paralogs for GMNN Gene

Paralogs for GMNN Gene

Pseudogenes.org Pseudogenes for GMNN Gene

genes like me logo Genes that share paralogs with GMNN: view

Variants for GMNN Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GMNN Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
1003567 Uncertain Significance: not provided 24,785,635(+) A/G
NM_015895.5(GMNN):c.469-3A>G
INTRON
1006625 Uncertain Significance: not provided 24,780,675(+) C/T
NM_015895.5(GMNN):c.64C>T (p.Pro22Ser)
MISSENSE
1031941 Pathogenic: Meier-gorlin syndrome 6 24,781,622(+) G/A
NM_015895.5(GMNN):c.274+1G>A
SPLICE_DONOR
rs145822661 Benign: not provided 24,784,139(+) G/A
NM_015895.5(GMNN):c.327G>A (p.Ala109=)
SYNONYMOUS
rs1581431798 Likely Benign: not provided 24,784,452(+) A/G
NM_015895.5(GMNN):c.366A>G (p.Lys122=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for GMNN Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for GMNN Gene

Variant ID Type Subtype PubMed ID
nsv508396 CNV deletion 20534489
nsv5227 CNV deletion 18451855
nsv830609 CNV gain 17160897

Variation tolerance for GMNN Gene

Residual Variation Intolerance Score: 73.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.74; 83.17% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GMNN Gene

Human Gene Mutation Database (HGMD)
GMNN
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GMNN
Leiden Open Variation Database (LOVD)
GMNN

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GMNN Gene

Disorders for GMNN Gene

MalaCards: The human disease database

(9) MalaCards diseases for GMNN Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search GMNN in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GEMI_HUMAN
  • Meier-Gorlin syndrome 6 (MGORS6) [MIM:616835]: A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. {ECO:0000269 PubMed:26637980}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for GMNN

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with GMNN: view

No data available for Genatlas for GMNN Gene

Publications for GMNN Gene

  1. Geminin, an inhibitor of DNA replication, is degraded during mitosis. (PMID: 9635433) McGarry TJ … Kirschner MW (Cell 1998) 2 3 4 22
  2. De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome. (PMID: 26637980) Burrage LC … Yang Y (American journal of human genetics 2015) 3 4 72
  3. Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing. (PMID: 19906994) De Marco V … Perrakis A (Proceedings of the National Academy of Sciences of the United States of America 2009) 3 4 22
  4. Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. (PMID: 14993212) Sugimoto N … Fujita M (The Journal of biological chemistry 2004) 3 4 22
  5. A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. (PMID: 15260975) Saxena S … Dutta A (Molecular cell 2004) 3 4 22

Products for GMNN Gene

Sources for GMNN Gene