# RNF43

Source: https://onco.cc/targets/rnf43/  
OnCo record `rnf43` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: ring finger protein 43; E3 ubiquitin-protein ligase RNF43; FLJ20315; RNF124; DKFZp781H0392
- Tags: cancer-genes-wave
- Symbol: RNF43
- Class: enzyme
- Biology: 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).
- Where found: Pancreatic ductal adenocarcinoma: IntOGen driver in 7 cohorts (PAAD, PANCREAS); Colorectal cancer: Open Targets association 0.65 with colorectal cancer (MONDO_0005575); IntOGen driver in 3 cohorts (COAD, COADREAD); Gastric & gastro-oesophageal junction cancer: Open Targets association 0.63 with gastric cancer (MONDO_0001056); IntOGen driver in 2 cohorts (STAD); Prostate cancer: Open Targets association 0.55 with prostate cancer (MONDO_0008315); IntOGen driver in 3 cohorts (PRAD, PROSTATE); Oesophageal cancer: IntOGen driver in 2 cohorts (ESCA); Ovarian cancer: Open Targets association 0.51 with ovarian cancer (MONDO_0008170); IntOGen driver in 1 cohort (OVT); Pancreatic ductal adenocarcinoma: inactivating mutation 5-8%; Colorectal cancer: inactivating mutation (g659fs hotspot) 5-12%

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 4 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 17 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Pancreatic ductal adenocarcinoma: inactivating mutations in 5 to 8% (cBioPortal), a recurrent driver in the TCGA analysis and part of the WNT pathway of the ten (Cancer Genome Atlas 2017, Bailey 2016). It was established as a suppressor of both IPMN (6 of 8) and mucinous cystic neoplasm (3 of 8) (Wu 2011, PNAS) and is largely confined to the non-invasive lesion during cyst progression (Noe 2020).
- Colorectal cancer: inactivating mutation in 5 to 12%, but 63.8% of MSI-high against 3.7% of microsatellite-stable samples in crc_msk_2026, because most calls are the G659fs coding-microsatellite frameshift. It is the WNT driver of the serrated and hypermutated route, where APC is often intact (Crockett and Nagtegaal 2019), and the entry point for porcupine inhibitors in trials.

## Sources

- HGNC HGNC:18505: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18505
- UniProt Q68DV7: https://www.uniprot.org/uniprotkb/Q68DV7/entry
- NCBI Gene 54894: https://www.ncbi.nlm.nih.gov/gene/54894
- Ensembl ENSG00000108375: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000108375

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- pathways: [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- key papers: [A combination of molecular markers and clinical features improve the classification of pancreatic cysts](https://onco.cc/key-papers/paper-springer-pancreatic-cyst-molecular-classification-gastroenterology-2015/), [Clinical sequencing defines the genomic landscape of metastatic colorectal cancer](https://onco.cc/key-papers/paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018/), [Genomic analyses identify molecular subtypes of pancreatic cancer](https://onco.cc/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/), [Genomic characterization of malignant progression in neoplastic pancreatic cysts](https://onco.cc/key-papers/paper-noe-cyst-malignant-progression-genomics-nat-commun-2020/), [Integrated genomic characterization of pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017/), [IPMNs with co-occurring invasive cancers: neighbours but not always relatives](https://onco.cc/key-papers/paper-felsenstein-ipmn-cooccurring-cancer-relatedness-gut-2018/), [Terminology, molecular features, epidemiology, and management of serrated colorectal neoplasia](https://onco.cc/key-papers/paper-crockett-nagtegaal-serrated-neoplasia-gastroenterology-2019/), [Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways](https://onco.cc/key-papers/paper-wu-pancreatic-cyst-exomes-rnf43-pnas-2011/), [Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets](https://onco.cc/key-papers/paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015/)

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