RNF43

Tumour Suppressor
E3 ubiquitin-protein ligase RNF43 UniProt accession Q68DV7

E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (PubMed:18313049, PubMed:22575959, PubMed:22895187). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (By similarity)

Source: UniProt

Interacts with AKAP8L, NONO and SFPQ (PubMed:18313049, PubMed:18655028). Interacts with FZD5 (PubMed:22895187). Identified in a complex composed of RNF43, LGR5 and RSPO1 (PubMed:23756651).

Interacts with RSPO2 (PubMed:29769720). Interacts with LMBR1L (By similarity)

Source: UniProt
Cell membrane — Single-pass type I membrane protein, Endoplasmic reticulum membrane — Single-pass type I membrane protein, Nucleus envelope
Source: UniProt

Expressed in fetal kidney, fetal lung, in colon cancer tissues, hepatocellular carcinomas and lung adenocarcinomas. Overexpressed in colorectal cancer cell lines

Source: UniProt
  • Sessile serrated polyposis cancer syndrome (SSPCS)

    A rare disease characterized by multiple and/or large serrated polyps developing in the colon, and an increased personal and familial risk of colorectal cancer. A patient is diagnosed with SSPCS if at least one of the following criteria is met: the presence of at least five sessile serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in diameter; the presence of any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis; the presence of more than 20 serrated polyps of any size distributed throughout the colon. Sessile serrated polyps are also known as sessile serrated adenomas (SSA) and are estimated to be responsible for 20 to 35% of all colon cancers.

    Individuals with SSPCS may have a strong personal or family history of extracolonic cancers.

Source: UniProt
  • Regulation of FZD by ubiquitination
  • Signaling by RNF43 mutants
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.19%
Lung Adenocarcinoma 0.87%
Lung Small Cell Carcinoma 1.19%
Lung Squamous Cell Carcinoma 0.68%
Oesophagus Adenocarcinoma 2.17%
Oesophagus Squamous Cell Carcinoma 0.59%
Pancreas Ductal Carcinoma 4.47%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to RNF43, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 4

NCT ID Condition Brief Title Phase Status
NCT04907851 Advanced Solid Tumours A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) PHASE2 COMPLETED
NCT00677287 Colorectal Cancer, Colon Cancer, Rectal Cancer Histocompatibility Leukocyte Antigen (HLA)-A*2402 Restricted Peptide Vaccine Therapy in Patients With Colorectal Cancer PHASE1, PHASE2 TERMINATED
NCT01351103 Pancreatic Cancer, BRAF Mutant Colorectal Cancer, Melanoma, Triple Negative Breast Cancer, Head and Neck Squamous Cell Cancer, Cervical Squamous Cell Cancer, Esophageal Squamous Cell Cancer, Lung Squamous Cell Cancer A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands PHASE1 COMPLETED
NCT04907539 Colorectal Cancer A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC) PHASE2 COMPLETED