RNF43: A Key Negative Regulator of Wnt Signaling in Cancer
Comprehensive genomic and functional overview of the RNF43 gene, its role in tumor suppression, and clinical implications.
Gene Information Card
| Symbol | RNF43 |
|---|---|
| Full Name | Ring Finger Protein 43 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q22 |
| NCBI Gene ID | 54894 ncbi.nlm.nih.gov/gene/54894 |
| Ensembl ID | ENSG00000108375 |
| UniProt ID | Q68DV7 |
| OMIM ID | 612482 |
| HGNC ID | 18505 |
| Aliases | RNF124, URCC, E3 ubiquitin-protein ligase RNF43 |
Description
RNF43 encodes a transmembrane E3 ubiquitin ligase that negatively regulates Wnt signaling by promoting the ubiquitination and degradation of Frizzled receptors. It acts as a tumor suppressor in various cancers, particularly in pancreatic and colorectal adenocarcinomas. Loss-of-function mutations in RNF43 lead to constitutive Wnt pathway activation and are frequently observed in serrated polyps and microsatellite-unstable colorectal cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic ductal adenocarcinoma | Loss-of-function mutations impair Frizzled degradation, leading to aberrant Wnt signaling | COSMIC, ClinVar |
| Colorectal adenocarcinoma (microsatellite unstable) | Frameshift mutations in coding mononucleotide repeats cause protein truncation and loss of function | ClinVar, NCBI |
| Sessile serrated adenoma/polyp | Inactivating mutations drive serrated neoplasia pathway | OMIM, NCBI |
| Mucinous cystic neoplasm of the pancreas | Recurrent RNF43 mutations contribute to cyst formation and malignant transformation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 11.2 | Medium |
| Pancreas | 8.5 | Medium |
| Stomach | 7.9 | Medium |
| Small intestine | 10.1 | Medium |
| Liver | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HCT116 (colorectal carcinoma) | 12.5 | Endogenous expression |
| PANC-1 (pancreatic carcinoma) | 9.8 | Endogenous expression |
| HEK293 (embryonic kidney) | 7.2 | Model cell line |
| SW480 (colorectal adenocarcinoma) | 6.4 | Reduced expression due to mutation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.953_954delAG | Frameshift | ~18% in MSI colorectal cancer | Loss of function |
| p.Gly659fs*41 | Frameshift | ~10% in pancreatic cancer | Loss of function |
| p.Arg117* | Nonsense | <5% in various cancers | Loss of function |
| p.Ser301* | Nonsense | <5% in gastric cancer | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most RNF43 mutations are loss-of-function, including frameshift, nonsense, and missense variants that disrupt the RING finger domain or cause protein truncation, leading to impaired ubiquitination of Frizzled receptors and constitutive Wnt signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations have been reported in RNF43.
Dominant Negative (DN)
Dominant-negative effects have not been established for RNF43 mutations; loss of heterozygosity is typically required for tumorigenesis.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity (GO:0004842) | • protein ubiquitination (GO:0016567) |
| • cytoplasm (GO:0005737) | • integral component of membrane (GO:0016021) |
| • canonical Wnt signaling pathway (GO:0060070) | • cell differentiation (GO:0030154) |
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• Signaling by WNT (Reactome: R-HSA-195721)
Protein Summary
RNF43 is a 783-amino acid transmembrane E3 ubiquitin ligase containing an N-terminal signal peptide, a RING-type zinc finger domain (residues 117–155), and a C-terminal cytoplasmic region. It localizes to the plasma membrane and endosomes, where it ubiquitinates Frizzled receptors, targeting them for lysosomal degradation. This negative feedback loop tightly regulates Wnt pathway activity. Loss of RNF43 function removes this brake, leading to uncontrolled cell proliferation and tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF43 Knockout HEK293 Cell Line | EDJ-KQ12180 | Human | 54894 | Details Get a Quote |
| RNF43 Knockout HeLa Cell Line | EDJ-KQ18150 | Human | 54894 | Details Get a Quote |
| RNF43 Knockout A-549 Cell Line | EDJ-KQ40898 | Human | 54894 | Details Get a Quote |
| RNF43 Knockout HCT 116 Cell Line | EDJ-KQ40899 | Human | 54894 | Details Get a Quote |
| RNF43 Knockout 5637 Cell Line | EDJ-KZ435 | Human | 54894 | Details Get a Quote |
| RNF43 Knockout AGS Cell Line | EDJ-KZ436 | Human | 54894 | Details Get a Quote |
| RNF43 Knockout HCA7 Cell Line | EDJ-KZ437 | Human | 54894 | Details Get a Quote |
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