This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of ... See more...

Aliases for GCKR Gene

Aliases for GCKR Gene

  • Glucokinase Regulator 2 3 4 5
  • Glucokinase Regulatory Protein 3 4
  • Hexokinase 4 Regulator 2 3
  • GKRP 3 4
  • Glucokinase (Hexokinase 4) Regulatory Protein 2
  • Glucokinase (Hexokinase 4) Regulator 3
  • FGQTL5 3

External Ids for GCKR Gene

Previous GeneCards Identifiers for GCKR Gene

  • GC02P027641
  • GC02P027812
  • GC02P027694
  • GC02P027631
  • GC02P027573
  • GC02P027720
  • GC02P027461

Summaries for GCKR Gene

Entrez Gene Summary for GCKR Gene

  • This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY). [provided by RefSeq, Jul 2008]

GeneCards Summary for GCKR Gene

GCKR (Glucokinase Regulator) is a Protein Coding gene. Diseases associated with GCKR include Fasting Plasma Glucose Level Quantitative Trait Locus 5 and Maturity-Onset Diabetes Of The Young. Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and Hexose transport. Gene Ontology (GO) annotations related to this gene include enzyme binding and protein domain specific binding.

UniProtKB/Swiss-Prot Summary for GCKR Gene

  • Regulates glucokinase (GCK) by forming an inactive complex with this enzyme (PubMed:23621087, PubMed:23733961). Acts by promoting GCK recruitment to the nucleus, possibly to provide a reserve of GCK that can be quickly released in the cytoplasm after a meal (PubMed:10456334). The affinity of GCKR for GCK is modulated by fructose metabolites: GCKR with bound fructose 6-phosphate has increased affinity for GCK, while GCKR with bound fructose 1-phosphate has strongly decreased affinity for GCK and does not inhibit GCK activity (PubMed:23621087, PubMed:23733961).

Additional gene information for GCKR Gene

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

Genomics for GCKR Gene

GeneHancer (GH) Regulatory Elements for GCKR Gene

Promoters and enhancers for GCKR Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J027493 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 -2.0 -1991 3.1 EP300 POLR2G FOXA1 ZBTB26 ZBTB25 TGIF2 ZBTB7A SKI TBX3 ZNF341 GCKR FNDC4 lnc-IFT172-1 SNX17 ENSG00000270210 IFT172
GH02J027496 Promoter/Enhancer 1.3 EPDnew ENCODE 500.7 +0.1 98 1 POLR2G KDM6A ZBTB25 TGIF2 ZBTB7A SKI TBX3 FOXA2 ZSCAN9 KMT2B GCKR FNDC4 lnc-IFT172-1 ENSG00000234072 GTF3C2 TMEM214 CAD EIF2B4 ATRAID GTF3C2-AS1
GH02J027427 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 10.6 -67.0 -67039 4.8 HNRNPK EP300 CTCF SIN3A NRF1 TCF12 POLR2G SP1 NCOR1 GTF2E2 NRBP1 lnc-PPM1G-3 SNX17 IFT172 GPN1 SUPT7L ZNF512 GTF3C2 CAD ENSG00000234072
GH02J027461 Enhancer 0.7 Ensembl ENCODE 10.8 -36.1 -36138 1.8 NCOR1 NFIC TAL1 HDAC2 TCF12 TEAD4 ARID1B CBFA2T2 SPI1 CBFA2T3 piR-31432-370 piR-40154-095 piR-40163-060 piR-53431-373 piR-52261-141 SNX17 FNDC4 GCKR IFT172 SLC4A1AP
GH02J027565 Enhancer 0.6 Ensembl ENCODE 10.6 +70.0 70044 2.3 FOS GATA2 JUN POLR2A FNDC4 IFT172 GCKR CCDC121 GPN1 KRTCAP3 NRBP1 RNU6-986P CGREF1 LOC100420668
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GCKR on UCSC Golden Path with GeneCards custom track

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

Top Transcription factor binding sites by QIAGEN in the GCKR gene promoter:
  • CREB
  • LCR-F1

Genomic Locations for GCKR Gene

Genomic Locations for GCKR Gene
chr2:27,496,839-27,523,689
(GRCh38/hg38)
Size:
26,851 bases
Orientation:
Plus strand
chr2:27,719,706-27,746,554
(GRCh37/hg19)
Size:
26,849 bases
Orientation:
Plus strand

Genomic View for GCKR Gene

Genes around GCKR on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for GCKR Gene

Proteins for GCKR Gene

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

    Protein Symbol:
    Q14397-GCKR_HUMAN
    Recommended name:
    Glucokinase regulatory protein
    Protein Accession:
    Q14397
    Secondary Accessions:
    • A1L4C2
    • B4DPQ2
    • Q53RY6
    • Q99522

    Protein attributes for GCKR Gene

    Size:
    625 amino acids
    Molecular mass:
    68685 Da
    Quaternary structure:
    • Interacts (fructose 6-phosphate bound form) with GCK.

    Three dimensional structures from OCA and Proteopedia for GCKR Gene

    Alternative splice isoforms for GCKR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GCKR Gene

Post-translational modifications for GCKR Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GCKR Gene

No data available for DME Specific Peptides for GCKR Gene

Domains & Families for GCKR Gene

Gene Families for GCKR Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for GCKR Gene

Blocks:
  • Sugar isomerase (SIS)
  • Glucokinase regulatory protein
  • Glucokinase regulatory protein, vertebrate
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GCKR Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ51268, highly similar to Glucokinase regulatory protein (B4DPQ2_HUMAN)
  • Glucokinase regulatory protein (GCKR_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14397

UniProtKB/Swiss-Prot:

GCKR_HUMAN :
  • Fructose 1-phosphate and fructose 6-phosphate compete for the same binding site.
  • Belongs to the GCKR family.
Domain:
  • Fructose 1-phosphate and fructose 6-phosphate compete for the same binding site.
Family:
  • Belongs to the GCKR family.
genes like me logo Genes that share domains with GCKR: view

Function for GCKR Gene

Molecular function for GCKR Gene

UniProtKB/Swiss-Prot Function:
Regulates glucokinase (GCK) by forming an inactive complex with this enzyme (PubMed:23621087, PubMed:23733961). Acts by promoting GCK recruitment to the nucleus, possibly to provide a reserve of GCK that can be quickly released in the cytoplasm after a meal (PubMed:10456334). The affinity of GCKR for GCK is modulated by fructose metabolites: GCKR with bound fructose 6-phosphate has increased affinity for GCK, while GCKR with bound fructose 1-phosphate has strongly decreased affinity for GCK and does not inhibit GCK activity (PubMed:23621087, PubMed:23733961).
GENATLAS Biochemistry:
glucokinase regulatory protein 69kDa,,interacting non-covalently with GCR and inhibiting it in presence of fructose-6-phosphate

Phenotypes From GWAS Catalog for GCKR Gene

Gene Ontology (GO) - Molecular Function for GCKR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004857 enzyme inhibitor activity IBA 21873635
GO:0005515 protein binding IPI 11522786
GO:0016301 kinase activity IEA --
GO:0019899 enzyme binding IBA 21873635
GO:0019904 protein domain specific binding IEA --
genes like me logo Genes that share ontologies with GCKR: view
genes like me logo Genes that share phenotypes with GCKR: view

Animal Models for GCKR Gene

MGI Knock Outs for GCKR:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for GCKR Gene

Localization for GCKR Gene

Subcellular locations from UniProtKB/Swiss-Prot for GCKR Gene

Cytoplasm. Nucleus. Mitochondrion. Note=Under low glucose concentrations, GCKR associates with GCK and the inactive complex is recruited to the hepatocyte nucleus. {ECO:0000269 PubMed:10456334}.

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 GCKR gene
Compartment Confidence
nucleus 5
mitochondrion 4
cytosol 4
extracellular 2
plasma membrane 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Intermediate filaments (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GCKR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm IBA,TAS --
GO:0005737 cytoplasm ISS --
GO:0005739 mitochondrion IBA 21873635
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with GCKR: view

Pathways & Interactions for GCKR Gene

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

Pathways by source for GCKR Gene

Gene Ontology (GO) - Biological Process for GCKR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0006110 regulation of glycolytic process TAS --
GO:0006606 protein import into nucleus ISS --
GO:0009750 response to fructose IDA 14627435
GO:0016310 phosphorylation IEA --
genes like me logo Genes that share ontologies with GCKR: view

No data available for SIGNOR curated interactions for GCKR Gene

Drugs & Compounds for GCKR Gene

(9) Drugs for GCKR Gene - From: ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
D-glucose Approved, Investigational, Vet_approved Pharma 0
Beta-D-Glucose Experimental Pharma 0
Glucose 6-phosphate Experimental Pharma 0
Nutrients Pharma 7358
Olive Pharma 406

(8) Additional Compounds for GCKR Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Alpha-D-Glucose
  • alpha-D-GLC
  • alpha-Dextrose
  • a-D-GLC
  • α-D-GLC
  • a-D-Glucose
492-62-6
genes like me logo Genes that share compounds with GCKR: view

Transcripts for GCKR Gene

mRNA/cDNA for GCKR Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

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

No ASD Table

Relevant External Links for GCKR Gene

GeneLoc Exon Structure for
GCKR

Expression for GCKR Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Liver (x39.5).

Protein differential expression in normal tissues from HIPED for GCKR Gene

This gene is overexpressed in Liver (68.4).

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



Protein tissue co-expression partners for GCKR Gene

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

SOURCE GeneReport for Unigene cluster for GCKR Gene:

Hs.89771

mRNA Expression by UniProt/SwissProt for GCKR Gene:

Q14397-GCKR_HUMAN
Tissue specificity: Found in liver and pancreas. Not detected in muscle, brain, heart, thymus, intestine, uterus, adipose tissue, kidney, adrenal, lung or spleen.

Evidence on tissue expression from TISSUES for GCKR Gene

  • Liver(4.7)
genes like me logo Genes that share expression patterns with GCKR: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for GCKR Gene

Orthologs for GCKR Gene

This gene was present in the common ancestor of chordates.

Orthologs for GCKR Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GCKR 31 30
  • 99.41 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GCKR 31 30
  • 89.12 (n)
OneToMany
-- 31
  • 84 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Gckr 30
  • 86.57 (n)
mouse
(Mus musculus)
Mammalia Gckr 17 31 30
  • 85.94 (n)
cow
(Bos Taurus)
Mammalia GCKR 31 30
  • 84.41 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GCKR 31
  • 80 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100493477 30
  • 56.69 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC68583 30
zebrafish
(Danio rerio)
Actinopterygii LOC100333044 30
  • 48.97 (n)
gckr 31
  • 42 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 33 (a)
OneToOne
Species where no ortholog for GCKR was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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 GCKR Gene

ENSEMBL:
Gene Tree for GCKR (if available)
TreeFam:
Gene Tree for GCKR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GCKR: view image

Paralogs for GCKR Gene

No data available for Paralogs for GCKR Gene

Variants for GCKR Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for GCKR Gene

GCKR_HUMAN-Q14397
Genetic variations in GCKR define the fasting plasma glucose levels quantitative trait locus 5 (FGQTL5) [MIM:613463] (PubMed:18556336, PubMed:18678614). The normal fasting plasma glucose level is defined as less than 100 mg glucose per deciliter plasma (5.55 mmol per liter). Higher fasting plasma glucose levels predict type 2 diabetes in young adults and increases the risk of mortality (PubMed:18556336, PubMed:18678614).

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

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
720149 Benign: not provided 27,507,752(+) T/C SYNONYMOUS_VARIANT
753143 Likely Benign: not provided 27,505,709(+) C/T INTRON_VARIANT
rs1260326 Association: Fasting plasma glucose level quantitative trait locus 5. - 27,508,073(+) T/Cp.Pro446Leu MISSENSE_VARIANT
rs146175795 Likely Pathogenic: Fasting plasma glucose level quantitative trait locus 5 27,498,276(+) G/A MISSENSE_VARIANT
rs375836361 Likely Pathogenic: not provided 27,497,334(+) C/T NONSENSE

Additional dbSNP identifiers (rs#s) for GCKR Gene

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

Variant ID Type Subtype PubMed ID
esv3590140 CNV loss 21293372
nsv817684 CNV gain 17921354

Variation tolerance for GCKR Gene

Residual Variation Intolerance Score: 55.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.69; 46.22% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GCKR Gene

Human Gene Mutation Database (HGMD)
GCKR
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GCKR

SNP Genotyping and Copy Number Assay Products

Disorders for GCKR Gene

MalaCards: The human disease database

(11) MalaCards diseases for GCKR Gene - From: OMIM, GTR, DISEASES, Novoseek, and GeneCards

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

Additional Disease Information for GCKR

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GCKR: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GCKR Gene

Publications for GCKR Gene

  1. Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations. (PMID: 18678614) Orho-Melander M … Kathiresan S (Diabetes 2008) 3 4 23 41 54
  2. The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population. (PMID: 18556336) Vaxillaire M … DESIR Study Group (Diabetes 2008) 3 4 23 41 54
  3. Organization of the human glucokinase regulator gene GCKR. (PMID: 9570959) Hayward BE … Bonthron DT (Genomics 1998) 2 3 4 23 54
  4. Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations. (PMID: 19937311) Takeuchi F … Kato N (Diabetologia 2010) 3 23 41 54
  5. Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples. (PMID: 20160193) Weissglas-Volkov D … Pajukanta P (Circulation. Cardiovascular genetics 2010) 3 23 41 54

Products for GCKR Gene

Sources for GCKR Gene