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RNF43 (E3 ubiquitin-protein ligase RNF43) is an enzyme. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Pancreatic ductal adenocarcinoma, Colorectal cancer, Gastric & gastro-oesophageal junction cancer and 5 more.
E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signalling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signalling pathway. Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification.
Open Targets scores its association with cancer at 0.82 (direct and indirect evidence; datatypes affected pathway 0.61, literature 0.98, genetic association 0.57, somatic mutation 0.97, animal model 0.68). IntOGen calls it a driver in 21 cohorts (4 activating, 17 loss-of-function), covering Cholangiocarcinoma, Colon Adenocarcinoma, Colorectal Adenocarcinoma, Oesophageal Adenocarcinoma, Lung Squamous Cell Carcinoma, Ovarian Epithelial Tumour and others.
In plain words · RNF43 (E3 ubiquitin-protein ligase RNF43) is an enzyme. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Pancreatic ductal adenocarcinoma, Colorectal cancer, Gastric & gastro-oesophageal junction cancer and 5 more.
RNF43 (E3 ubiquitin-protein ligase RNF43) is an enzyme. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Pancreatic ductal adenocarcinoma, Colorectal cancer, Gastric & gastro-oesophageal junction cancer and 5 more.
E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signalling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled.
No product in this corpus aims at RNF43 yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
First described 2004. Earliest sequence paper UniProt cites for the protein: Yagyu et al, Int. J. Oncol, 2004, "A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer". Source.
Sources: HGNC HGNC:18505 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q68DV7 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000108375 (association with cancer (MONDO_0004992) 0.82; per-cancer scores at or above 0.5: colorectal cancer 0.65, gastric cancer 0.63, prostate cancer 0.55, ovarian cancer 0.51, skin cancer 0.52, lung cancer 0.56 (GraphQL API, CC0)); IntOGen RNF43 (driver in 21 cohorts (Act 4, LoF 17); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signalling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signalling pathway. Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification. Location: Cell membrane; Endoplasmic reticulum membrane; Nucleus envelope (UniProt). Locus 17q22 (HGNC).
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 5-12% | Inactivating mutation (G659fs hotspot) | cBioPortal: 734 of 7,237, 10.1%, in crc_msk_2026; 95 of 1,134, 8.4%, in crc_msk_2017; 105 of 1,516, 6.9%, in crc_eo_2020; 46 of 534, 8.6%, in coadread_tcga_pan_can_atlas_2018; 72 of 619, 11.6%, in coadread_dfci_2016. | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 5-8% | Inactivating mutation | cBioPortal: 142 of 2,336, 6.1%, in pdac_msk_2024; 30 of 395, 7.6%, in pancreas_msk_2024; 11 of 179, 6.1%, in paad_tcga_pan_can_atlas_2018; 21 of 383, 5.5%, in paad_qcmg_uq_2016; 9 of 140, 6.4%, in paad_cptac_2021; 6 of 109 in paad_utsw_2015. Mutated in 6 of 8 IPMNs and 3 of 8 MCNs, establishing it as a suppressor of both (Wu 2011, PNAS); RNF43 alterations were largely confined to the non-invasive lesions in cyst progression (Noe 2020); a recurrent gene in TCGA (Cancer Genome Atlas 2017) and part of the WNT pathway of the ten (Bailey 2016). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It gives surveillance a target and a timetable: catch high-grade dysplasia and there are about three years before invasion, and TGF-beta pathway loss is the event to detect.
It links the molecular route to the practical failure mode: interval cancers after a clear colonoscopy are disproportionately serrated, so detection quality is a molecular problem as much as a technical one.
It turned sidedness from an epidemiological curiosity into a mechanistic statement, and it is the reason a wild-type mitogenic report on a left-sided tumour is read as ligand dependence rather than as an absence.
Risk stratification of a cyst cannot assume the nearby cancer came from it, and the whole gland stays at risk after cyst resection.
It is the reference multi-platform dataset and the reason a KRAS wild-type report is treated as a search for another driver rather than as an absence.
With Moffitt's classical and basal-like split (the squamous and basal-like groups overlap) this fixed the molecular vocabulary of the disease and gave Precision-Panc and the UK's Glasgow group their trial framework.
The evidence that molecular cyst-fluid testing can spare operations, now part of specialist practice although not a universal standard.
The microdissected cohort is the cleanest exome reference for allele-level KRAS and copy-number calls, and it first tied MYC amplification to the squamous, chemotherapy-resistant end of the disease.
Query for this target: (TITLE:"RNF43" OR ABSTRACT:"RNF43" OR TITLE:"ring finger protein 43" OR ABSTRACT:"ring finger protein 43" OR TITLE:"E3 ubiquitin-protein ligase RNF43" OR ABSTRACT:"E3 ubiquitin-protein ligase RNF43" OR TITLE:"FLJ20315" OR ABSTRACT:"FLJ20315" OR TITLE:"RNF124" OR ABSTRACT:"RNF124" OR TITLE:"DKFZp781H0392" OR ABSTRACT:"DKFZp781H0392") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about RNF43, not a curated reading list.
Shares Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways, A combination of molecular markers and clinical features improve the classification of pancreatic cysts, Clinical sequencing defines the genomic landscape of metastatic colorectal cancer, Integrated genomic characterization of pancreatic ductal adenocarcinoma.
Shares IPMNs with co-occurring invasive cancers: neighbours but not always relatives, A combination of molecular markers and clinical features improve the classification of pancreatic cysts, Integrated genomic characterization of pancreatic ductal adenocarcinoma, Oesophageal cancer.
Shares Genomic characterization of malignant progression in neoplastic pancreatic cysts, Integrated genomic characterization of pancreatic ductal adenocarcinoma, Oesophageal cancer, IntOGen.
Shares IPMNs with co-occurring invasive cancers: neighbours but not always relatives, Genomic characterization of malignant progression in neoplastic pancreatic cysts, A combination of molecular markers and clinical features improve the classification of pancreatic cysts, Clinical sequencing defines the genomic landscape of metastatic colorectal cancer.
Shares Genomic analyses identify molecular subtypes of pancreatic cancer, Oesophageal cancer, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Integrated genomic characterization of pancreatic ductal adenocarcinoma, Genomic analyses identify molecular subtypes of pancreatic cancer, Endometrial cancer, IntOGen.
Shares Wnt / β-catenin, IntOGen, Open Targets Platform, Prostate cancer.
Shares Terminology, molecular features, epidemiology, and management of serrated colorectal neoplasia, A combination of molecular markers and clinical features improve the classification of pancreatic cysts, Gastric & gastro-oesophageal junction cancer, Pancreatic ductal adenocarcinoma.