The protein encoded by this gene is actually a preproprotein that is cleaved into four distinct mature peptides. One of these, glucagon, is a pancreatic hormone that counteracts the glucose-lowering action of insulin by stimulating glycogenolysis and gluconeogenesis. Glucagon is a ligand for a specific G-protein linked receptor whose signalling pathway controls cell proliferati... See more...

Aliases for GCG Gene

Aliases for GCG Gene

  • Glucagon 2 3 4 5
  • Glicentin-Related Polypeptide 2 3
  • Glucagon-Like Peptide 1 2 3
  • Glucagon-Like Peptide 2 2 3
  • Preproglucagon 2 3
  • GLP-1 3
  • GLP1 3
  • GLP2 3
  • GRPP 3

External Ids for GCG Gene

Previous GeneCards Identifiers for GCG Gene

  • GC02M161053
  • GC02M161527
  • GC02M162963
  • GC02M163201
  • GC02M162824
  • GC02M162707
  • GC02M154881

Summaries for GCG Gene

Entrez Gene Summary for GCG Gene

  • The protein encoded by this gene is actually a preproprotein that is cleaved into four distinct mature peptides. One of these, glucagon, is a pancreatic hormone that counteracts the glucose-lowering action of insulin by stimulating glycogenolysis and gluconeogenesis. Glucagon is a ligand for a specific G-protein linked receptor whose signalling pathway controls cell proliferation. Two of the other peptides are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms. Finally, the fourth peptide is similar to glicentin, an active enteroglucagon. [provided by RefSeq, Jul 2008]

GeneCards Summary for GCG Gene

GCG (Glucagon) is a Protein Coding gene. Diseases associated with GCG include Dumping Syndrome and Hyperglycemia. Among its related pathways are Signaling by GPCR and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Gene Ontology (GO) annotations related to this gene include identical protein binding and hormone activity.

UniProtKB/Swiss-Prot Summary for GCG Gene

  • Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.
  • GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis.
  • GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.
  • Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.
  • Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.

Gene Wiki entry for GCG Gene

Additional gene information for GCG Gene

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

Genomics for GCG Gene

GeneHancer (GH) Regulatory Elements for GCG Gene

Promoters and enhancers for GCG 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
GH02J162152 Promoter 0.3 EPDnew 500.7 +0.1 137 0.1 GCG lnc-FAP-2 LOC101929532
GH02J162126 Enhancer 0.8 Ensembl ENCODE 12.2 +26.5 26504 3 EP300 BCL11A CTCF ARNT MEF2B NBN SPI1 IRF4 POU2F2 IKZF1 GCG DPP4 ENSG00000224076 ENSG00000251621 SLC4A10 TIMM8AP1 LOC101929532 lnc-FAP-2
GH02J162211 Enhancer 0.2 dbSUPER 11.3 -60.1 -60119 1.5 FAP GCG ENSG00000236841 lnc-GCG-2 NONHSAG029689.2
GH02J162146 Enhancer 0.3 Ensembl 0.4 +5.2 5203 0.8 FOXA2 JUND lnc-FAP-2 GCG LOC101929532
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GCG on UCSC Golden Path with GeneCards custom track

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

Top Transcription factor binding sites by QIAGEN in the GCG gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • CREB
  • deltaCREB

Genomic Locations for GCG Gene

Genomic Locations for GCG Gene
chr2:162,142,869-162,152,404
(GRCh38/hg38)
Size:
9,536 bases
Orientation:
Minus strand
chr2:162,999,385-163,008,914
(GRCh37/hg19)
Size:
9,530 bases
Orientation:
Minus strand

Genomic View for GCG Gene

Genes around GCG on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for GCG Gene

Proteins for GCG Gene

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

    Protein Symbol:
    P01275-GLUC_HUMAN
    Recommended name:
    Glucagon
    Protein Accession:
    P01275
    Secondary Accessions:
    • A6NN65
    • Q53TP6

    Protein attributes for GCG Gene

    Size:
    180 amino acids
    Molecular mass:
    20909 Da
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • In the glucagon antagonist, His-53 and Phe-58 are missing. This antagonist has been successfully utilized to reduce glucose concentration in vivo.

    Three dimensional structures from OCA and Proteopedia for GCG Gene

neXtProt entry for GCG Gene

Post-translational modifications for GCG Gene

  • Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GCG Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for GCG Gene

Domains & Families for GCG Gene

Gene Families for GCG Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted secreted proteins

Protein Domains for GCG Gene

Blocks:
  • Glucagon/GIP/secretin/VIP
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GCG Gene

GenScript: Design optimal peptide antigens:
  • Glucagon (GLUC_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P01275

UniProtKB/Swiss-Prot:

GLUC_HUMAN :
  • Belongs to the glucagon family.
Family:
  • Belongs to the glucagon family.
genes like me logo Genes that share domains with GCG: view

Function for GCG Gene

Molecular function for GCG Gene

UniProtKB/Swiss-Prot Function:
Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.
UniProtKB/Swiss-Prot Function:
GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis.
UniProtKB/Swiss-Prot Function:
GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.
UniProtKB/Swiss-Prot Function:
Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.
UniProtKB/Swiss-Prot Function:
Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.
UniProtKB/Swiss-Prot Induction:
Glucagon release is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin. GLP-1 and GLP-2 are induced in response to nutrient ingestion.
GENATLAS Biochemistry:
glucagon,including glucagon related peptides I and II,enteroglucagon,glicentin,same as glucagon

Phenotypes From GWAS Catalog for GCG Gene

Gene Ontology (GO) - Molecular Function for GCG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding TAS 9990065
GO:0005179 hormone activity IBA 21873635
GO:0005515 protein binding IPI 17051221
GO:0031769 glucagon receptor binding IBA 21873635
GO:0042802 identical protein binding IPI 22212535
genes like me logo Genes that share ontologies with GCG: view
genes like me logo Genes that share phenotypes with GCG: view

Animal Model Products

CRISPR Products

miRNA for GCG Gene

miRTarBase miRNAs that target GCG

Inhibitory RNA Products

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

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for GCG Gene

Localization for GCG Gene

Subcellular locations from UniProtKB/Swiss-Prot for GCG Gene

Secreted.

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 GCG gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 5
plasma membrane 3
mitochondrion 3
nucleus 3
cytosol 3
cytoskeleton 2
peroxisome 2
endosome 2
lysosome 2
golgi apparatus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GCG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA 21873635
GO:0005737 cytoplasm IEA --
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0034774 secretory granule lumen TAS --
genes like me logo Genes that share ontologies with GCG: view

Pathways & Interactions for GCG Gene

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

Pathways by source for GCG Gene

3 Qiagen pathways for GCG Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • cAMP Pathway
1 Cell Signaling Technology pathway for GCG Gene

SIGNOR curated interactions for GCG Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for GCG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007186 G protein-coupled receptor signaling pathway TAS 7929237
GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway IBA 21873635
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway IEA --
GO:0007631 feeding behavior TAS 8538742
GO:0010737 protein kinase A signaling IBA 21873635
genes like me logo Genes that share ontologies with GCG: view

Drugs & Compounds for GCG Gene

(78) Drugs for GCG Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clozapine Approved Pharma Antagonist, Positive, Allosteric regulator, Full agonist, Agonist, Inverse agonist Antipsychotic medication 134
Olanzapine Approved, Investigational Pharma Antagonist, Full agonist, Agonist, Inverse agonist 437

(35) Additional Compounds for GCG Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GCG: view

Transcripts for GCG Gene

mRNA/cDNA for GCG Gene

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

CRISPR Products

Inhibitory RNA Products

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

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

No ASD Table

Relevant External Links for GCG Gene

GeneLoc Exon Structure for
GCG

Expression for GCG Gene

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

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

This gene is overexpressed in Pancreas (x48.5).

Protein differential expression in normal tissues from HIPED for GCG Gene

This gene is overexpressed in Islet of Langerhans (60.7) and Pancreas (6.9).

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



Protein tissue co-expression partners for GCG Gene

- Elite partner

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

SOURCE GeneReport for Unigene cluster for GCG Gene:

Hs.516494

mRNA Expression by UniProt/SwissProt for GCG Gene:

P01275-GLUC_HUMAN
Tissue specificity: Glucagon is secreted in the A cells of the islets of Langerhans. GLP-1, GLP-2, oxyntomodulin and glicentin are secreted from enteroendocrine cells throughout the gastrointestinal tract. GLP-1 and GLP-2 are also secreted in selected neurons in the brain.

Evidence on tissue expression from TISSUES for GCG Gene

  • Pancreas(5)
  • Intestine(4.7)
  • Liver(4.7)
  • Blood(3.6)
  • Stomach(3.3)
  • Nervous system(3.3)
  • Kidney(3.2)
  • Muscle(2.7)
  • Adrenal gland(2.5)
  • Heart(2.5)
  • Thyroid gland(2.4)
  • Skin(2.2)
  • Urine(2)
genes like me logo Genes that share expression patterns with GCG: view

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

Orthologs for GCG Gene

This gene was present in the common ancestor of chordates.

Orthologs for GCG Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GCG 31
  • 100 (a)
OneToOne
dog
(Canis familiaris)
Mammalia GLP-1 31
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Gcg 31
  • 89 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GCG 31
  • 85 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GCG 31
  • 62 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GCG 31
  • 34 (a)
OneToOne
chicken
(Gallus gallus)
Aves GCG 31
  • 65 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GCG 31
  • 77 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia gcg-A 30
zebrafish
(Danio rerio)
Actinopterygii gcgb 31 30
  • 63.66 (n)
OneToMany
gcga 31
  • 46 (a)
OneToMany
Species where no ortholog for GCG 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)
  • 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)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for GCG Gene

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

Paralogs for GCG Gene

No data available for Paralogs for GCG Gene

Variants for GCG Gene

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

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs5650 - p.Ala115Val

Additional dbSNP identifiers (rs#s) for GCG Gene

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

Variant ID Type Subtype PubMed ID
nsv834439 CNV gain 17160897
nsv834440 CNV gain 17160897

Variation tolerance for GCG Gene

Residual Variation Intolerance Score: 59.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.41; 9.00% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GCG Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GCG

SNP Genotyping and Copy Number Assay Products

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

Disorders for GCG Gene

MalaCards: The human disease database

(92) MalaCards diseases for GCG Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
dumping syndrome
  • dumping syndrome
hyperglycemia
hypoglycemia
  • hypoglycaemia
short bowel syndrome
  • acquired short bowel syndrome
glucose intolerance
  • glucose: intolerance
- elite association - COSMIC cancer census association via MalaCards
Search GCG in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GCG

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 GCG: view

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

Publications for GCG Gene

  1. Expression, purification, and PC1-mediated processing of human proglucagon, glicentin, and major proglucagon fragment. (PMID: 12651102) Bonic A … Mackin RB (Protein expression and purification 2003) 3 4 23 54
  2. Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. (PMID: 14632334) Tadokoro R … Yamashiro Y (Acta paediatrica (Oslo, Norway : 1992) 2003) 3 4 23 54
  3. Role of the prohormone convertase PC2 in the processing of proglucagon to glucagon. (PMID: 9287128) Rouillé Y … Halban PA (FEBS letters 1997) 3 4 23 54
  4. Complete sequences of glucagon-like peptide-1 from human and pig small intestine. (PMID: 2753890) Orskov C … Holst JJ (The Journal of biological chemistry 1989) 2 3 4 54
  5. Structure of the human glucagon gene. (PMID: 3725587) White JW … Saunders GF (Nucleic acids research 1986) 2 3 4 54

Products for GCG Gene

Sources for GCG Gene