GUCY2C (Guanylate Cyclase 2C) - A Key Receptor in Intestinal Homeostasis and Colorectal Cancer
Explore the genomic, functional, and clinical significance of GUCY2C, a membrane-bound guanylate cyclase implicated in intestinal disorders and cancer.
Gene Information Card
| Symbol | GUCY2C |
|---|---|
| Full Name | Guanylate Cyclase 2C (also known as Guanylyl Cyclase C) |
| Gene Type | Protein coding |
| Chromosomal Location | 12p12.3 (GRCh38) |
| NCBI Gene ID | 2984 ncbi.nlm.nih.gov/gene/2984 |
| Ensembl ID | ENSG00000070019 |
| UniProt ID | P25092 |
| OMIM ID | 601330 |
| HGNC ID | 4688 |
| Aliases | GUC2C, STAR, GC-C, Guanylyl cyclase C, Heat-stable enterotoxin receptor, Intestinal guanylate cyclase |
Description
GUCY2C encodes guanylate cyclase C, a transmembrane receptor predominantly expressed in intestinal epithelial cells. It binds endogenous ligands (guanylin and uroguanylin) and bacterial heat-stable enterotoxins (STa), activating intracellular cGMP signaling. This pathway regulates fluid and electrolyte homeostasis, cell proliferation, and apoptosis. GUCY2C is a well-established marker for colorectal cancer metastases and a target for vaccine and therapeutic strategies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | GUCY2C is overexpressed in colorectal tumors and metastases; loss of GUCY2C signaling (via silencing or mutation) may promote tumorigenesis by reducing cGMP-mediated growth suppression. | Multiple studies (e.g., PubMed PMID: 25652204, 27641680) show GUCY2C expression in >95% of colorectal cancers; loss of ligand expression is common. |
| Hereditary Diarrheal Illness (Congenital Sodium Diarrhea) | Biallelic loss-of-function mutations in GUCY2C cause congenital sodium diarrhea, due to impaired electrolyte absorption in the intestine. | ClinVar and OMIM entries (OMIM #601330) list pathogenic variants; functional studies confirm loss of guanylate cyclase activity. |
| Infectious Diarrhea (Enterotoxigenic E. coli) | Bacterial STa toxin binds GUCY2C, causing excessive cGMP production and secretory diarrhea. | Well-established mechanism; GUCY2C is the known receptor for STa (UniProt annotation). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | High (nTPM ~ 200-300) | Predominant expression in enterocytes |
| Colon | High (nTPM ~ 150-250) | Strong expression in colonic epithelium |
| Rectum | High (nTPM ~ 100-200) | Consistent with intestinal lineage |
| Stomach | Low (nTPM < 10) | Minimal expression |
| Other tissues | Very low/absent | Not detected in most normal tissues |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | High | Colorectal adenocarcinoma cell line; used as model for intestinal epithelium |
| HT-29 | Moderate | Colorectal adenocarcinoma cell line |
| SW480 | Low | Colorectal adenocarcinoma cell line; lower expression compared to Caco-2 |
| HCT116 | Moderate | Colorectal carcinoma cell line |
| LoVo | Moderate | Colorectal adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1018C>T (p.Arg340*) | Nonsense | Rare (found in congenital sodium diarrhea) | Loss of function; truncated protein lacking catalytic domain |
| c.1243G>A (p.Gly415Arg) | Missense | Rare (pathogenic in congenital sodium diarrhea) | Loss of function; disrupts ligand binding or catalytic activity |
| c.1456C>T (p.Arg486Trp) | Missense | Rare (likely pathogenic) | Loss of function; affects protein stability |
| c.1741G>A (p.Gly581Ser) | Missense | Rare (uncertain significance) | Unknown; may affect dimerization |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish guanylate cyclase activity, leading to impaired cGMP production. These are associated with congenital sodium diarrhea and may contribute to colorectal cancer progression when silenced.
Gain of Function (GOF)
Activating mutations are not commonly reported in GUCY2C; however, overexpression in tumors can be considered a gain-of-function at the expression level, not via mutation.
Dominant Negative (DN)
No clear dominant-negative mutations have been described for GUCY2C; most pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • guanylate cyclase activity (GO:0004383) | • ATP binding (GO:0005524) |
| • plasma membrane (GO:0005886) | • signal transduction (GO:0007165) |
| • cGMP biosynthetic process (GO:0006182) | • protein binding (GO:0005515) |
| • integral component of membrane (GO:0016021) |
Pathways
• cGMP signaling pathway (Reactome: R-HSA-418457)
• Guanylate cyclase pathway (KEGG: map00230)
• Heat-stable enterotoxin (STa) signaling (via GUCY2C)
Protein Summary
GUCY2C is a 1073-amino acid single-pass type I membrane protein with an extracellular ligand-binding domain, a single transmembrane region, and an intracellular guanylate cyclase catalytic domain. It exists as a homodimer. Upon ligand binding (guanylin, uroguanylin, or STa), it catalyzes the conversion of GTP to cGMP, activating protein kinase G (PKG) and cyclic nucleotide-gated channels. This regulates ion transport and cell proliferation. The protein is heavily glycosylated and expressed on the apical surface of intestinal epithelial cells. Its extracellular domain is a target for antibody-based therapies in colorectal cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GUCY2C Knockout HEK293 Cell Line | EDJ-KQ17715 | Human | 2984 | Details Get a Quote |
| GUCY2C Knockout HeLa Cell Line | EDJ-KQ53462 | Human | 2984 | Details Get a Quote |
| GUCY2C Knockout A-549 Cell Line | EDJ-KQ61934 | Human | 2984 | Details Get a Quote |
| GUCY2C Knockout HCT 116 Cell Line | EDJ-KQ70415 | Human | 2984 | Details Get a Quote |
