GUCA2A (Guanylate Cyclase Activator 2A)
Endogenous ligand for guanylate cyclase-C; regulates intestinal fluid and electrolyte homeostasis
Gene Information Card
| Symbol | GUCA2A |
|---|---|
| Full Name | Guanylate Cyclase Activator 2A (Guanylin) |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.2 |
| NCBI Gene ID | 2980 ncbi.nlm.nih.gov/gene/2980 |
| Ensembl ID | ENSG00000197273 |
| UniProt ID | Q02747 |
| OMIM ID | 601271 |
| HGNC ID | 4682 |
| Aliases | GUCA2, guanylin |
Description
GUCA2A encodes guanylin, a 15-amino acid peptide hormone that acts as an endogenous ligand for guanylate cyclase-C (GUCY2C). Guanylin is primarily expressed in intestinal epithelial cells and regulates fluid and electrolyte secretion by activating cGMP-dependent signaling pathways. This gene plays a critical role in maintaining intestinal homeostasis, and its dysregulation is implicated in diarrheal diseases and colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Diarrheal disorders (e.g., infectious diarrhea) | Guanylin overproduction or exogenous bacterial toxins (e.g., STa) mimic guanylin, causing excessive cGMP-driven chloride and water secretion into the intestinal lumen. | ClinVar, OMIM |
| Colorectal cancer | Loss of GUCA2A expression or silencing leads to reduced GUCY2C activation, promoting tumorigenesis through disrupted cGMP signaling and increased proliferation. | COSMIC, PubMed |
| Meconium ileus in cystic fibrosis | Altered guanylin expression contributes to abnormal intestinal fluid secretion in CF patients. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 112.3 | High |
| Colon | 89.7 | High |
| Rectum | 76.5 | High |
| Stomach | 12.1 | Low |
| Kidney | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (colorectal adenocarcinoma) | 45.6 | Moderate expression |
| HT-29 (colorectal adenocarcinoma) | 38.2 | Moderate expression |
| SW480 (colorectal adenocarcinoma) | 22.1 | Low expression |
| HCT 116 (colorectal carcinoma) | 15.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.152G>A (p.Arg51Gln) | Missense | <0.01% (rare) | Reduced peptide stability and receptor binding affinity |
| c.208C>T (p.Arg70*) | Nonsense | <0.01% (rare) | Premature truncation, loss of function |
| c.3G>A (p.Met1?) | Start loss | <0.01% (rare) | No protein translation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations (e.g., p.Arg70*, p.Met1?) result in absent or truncated guanylin, impairing GUCY2C activation and intestinal fluid regulation.
Gain of Function (GOF)
Not reported; gain-of-function mutations are not documented for GUCA2A.
Dominant Negative (DN)
Not reported; no dominant-negative variants have been described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Guanylate cyclase-C signaling pathway (Reactome: R-HSA-418594)
• cGMP-mediated signaling (KEGG: hsa04022)
• Intestinal fluid and electrolyte transport (NCBI GeneRIF)
Protein Summary
Guanylin is a 15-amino acid secreted peptide derived from a 115-residue precursor (proguanylin). It contains four conserved cysteine residues forming two disulfide bonds essential for receptor binding. The mature peptide binds to and activates guanylate cyclase-C (GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells. Activation elevates intracellular cGMP, leading to phosphorylation of CFTR and other ion transporters, resulting in chloride and bicarbonate secretion and inhibition of sodium absorption. This mechanism is critical for intestinal fluid homeostasis and is exploited by bacterial enterotoxins (e.g., STa) to cause secretory diarrhea.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GUCA2A Knockout HEK293 Cell Line | EDJ-KQ4818 | Human | 2980 | Details Get a Quote |
| GUCA2A Knockout HeLa Cell Line | EDJ-KQ53458 | Human | 2980 | Details Get a Quote |
| GUCA2A Knockout A-549 Cell Line | EDJ-KQ61931 | Human | 2980 | Details Get a Quote |
| GUCA2A Knockout HCT 116 Cell Line | EDJ-KQ70411 | Human | 2980 | Details Get a Quote |
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