GCG (Glucagon) Gene

Key regulator of glucose homeostasis and energy metabolism

Gene Information Card

Symbol GCG
Full Name Glucagon
Gene Type protein-coding
Chromosomal Location 2q24.2
NCBI Gene ID 2641 ncbi.nlm.nih.gov/gene/2641
Ensembl ID ENSG00000115263
UniProt ID P01275
OMIM ID 138030
HGNC ID 4191
Aliases GLP1, GLP2, GRPP, Glicentin, Oxyntomodulin

Description

The GCG gene encodes preproglucagon, a precursor protein that is cleaved into multiple bioactive peptides including glucagon, glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), glicentin, oxyntomodulin, and major proglucagon fragment. Glucagon is a key counter-regulatory hormone to insulin, promoting glycogenolysis and gluconeogenesis in the liver to raise blood glucose levels. GLP-1 and GLP-2 are incretins involved in insulin secretion and intestinal growth, respectively. Dysregulation of GCG expression or processing is implicated in diabetes, glucagonoma, and other metabolic disorders.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Glucagonoma Excessive secretion of glucagon from pancreatic alpha-cell tumors leads to hyperglycemia and characteristic rash (necrolytic migratory erythema). OMIM #138030; ClinVar; COSMIC
Diabetes Mellitus (type 2) Impaired suppression of glucagon secretion contributes to hyperglycemia; GCG variants may alter glucose homeostasis. NCBI Gene; ClinVar
Hyperglucagonemia Elevated circulating glucagon levels due to GCG gene mutations or altered processing, associated with glucose intolerance. OMIM; ClinVar

Expression Profile

Tissue Expression
Tissue nTPM level
Pancreas 125.6 High
Stomach 10.2 Medium
Small Intestine 8.5 Medium
Colon 3.1 Low
Brain 1.2 Low
Cell Line Expression
Cell Line nTPM Notes
Alpha-TC1.6 (mouse pancreatic alpha cell) High Model for glucagon secretion studies
InR1-G9 (hamster pancreatic alpha cell) High Used in GCG expression analysis
HEK293 Low Transient expression studies
Data source：Human Protein Atlas（proteinatlas.org）

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.79G>A (p.Gly27Arg) Missense <0.01% Altered proglucagon processing; associated with hyperglucagonemia
c.112C>T (p.Arg38Trp) Missense <0.01% Impaired GLP-1 secretion; linked to glucose intolerance
c.199C>T (p.Arg67Cys) Missense <0.01% Reduced glucagon activity; reported in familial hyperglucagonemia
Mutation functional classification

Loss of Function (LOF)

Mutations impairing proglucagon cleavage or receptor binding reduce glucagon or GLP-1 activity, leading to hypoglycemia or impaired incretin effect.

Gain of Function (GOF)

Activating mutations increase glucagon secretion or activity, contributing to hyperglycemia and glucagonoma.

Dominant Negative (DN)

Rare; some missense variants may interfere with proglucagon processing in a dominant-negative manner.
View complete mutation data：
ClinVar：https://www.clinvar.com/gene/2641
COSMIC：https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=GCG

Gene Ontology (GO)

• hormone activity (GO:0005179) • extracellular region (GO:0005576)
• G protein-coupled receptor signaling pathway (GO:0007186) • response to insulin (GO:0032868)
• glucose homeostasis (GO:0042593) • identical protein binding (GO:0042802)

Pathways

• Glucagon signaling pathway (KEGG: hsa04922)
• Type II diabetes mellitus (KEGG: hsa04930)
• Insulin secretion (KEGG: hsa04911)
• GPCR downstream signaling (Reactome: R-HSA-388396)

Protein Summary

The GCG gene product, preproglucagon (180 amino acids), is processed tissue-specifically into glucagon (29 aa) in pancreatic alpha cells, and into GLP-1 (30 aa) and GLP-2 (33 aa) in intestinal L cells and brain. Glucagon binds to the glucagon receptor (GCGR) to stimulate hepatic glucose output. GLP-1 enhances insulin secretion and suppresses appetite. The protein contains conserved prohormone convertase cleavage sites. UniProt ID: P01275.

Related Services

Knockout Cell Line
Point Mutation Cell Line
Knock-In Cell Line
Overexpression Cell Line
Knockdown Cell Line
Reporter Cell Line
Knock-in Tag
iPSC Gene Editing

Related Products

Product name Cat.No. Species Gene ID
GCG Knockout HEK293 Cell Line EDJ-KQ1765 Human 2641 Details Get a Quote
UGCG Knockout HEK293 Cell Line EDJ-KQ2506 Human 7357 Details Get a Quote
SGCG Knockout HEK293 Cell Line EDJ-KQ2755 Human 6445 Details Get a Quote
GCGR Knockout HEK293 Cell Line EDJ-KQ4690 Human 2642 Details Get a Quote
UGCG Knockout A-549 Cell Line EDJ-KQ23102 Human 7357 Details Get a Quote
UGCG Knockout HCT 116 Cell Line EDJ-KQ23103 Human 7357 Details Get a Quote
UGCG Knockout HeLa Cell Line EDJ-KQ23104 Human 7357 Details Get a Quote
GCG Knockout HeLa Cell Line EDJ-KQ53314 Human 2641 Details Get a Quote
GCGR Knockout HeLa Cell Line EDJ-KQ53315 Human 2642 Details Get a Quote
SGCG Knockout HeLa Cell Line EDJ-KQ54456 Human 6445 Details Get a Quote
GCG Knockout A-549 Cell Line EDJ-KQ61797 Human 2641 Details Get a Quote
GCGR Knockout A-549 Cell Line EDJ-KQ61798 Human 2642 Details Get a Quote
SGCG Knockout A-549 Cell Line EDJ-KQ62944 Human 6445 Details Get a Quote
GCG Knockout HCT 116 Cell Line EDJ-KQ70282 Human 2641 Details Get a Quote
GCGR Knockout HCT 116 Cell Line EDJ-KQ70283 Human 2642 Details Get a Quote
Displaying Records 1 To 15 Of 16 Records

Reference Databases

NCBI Gene https://www.ncbi.nlm.nih.gov/gene/2641
OMIM https://www.omim.org/entry/138030
HGNC https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4191
Ensembl https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000115263
UniProt https://www.uniprot.org/uniprot/P01275
ClinVar https://www.ncbi.nlm.nih.gov/clinvar/?term=GCG%5Bgene%5D
COSMIC https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=GCG
Contact Us
*
*
*
*
How did you hear about us：
✖ service online