# ZNRF3

Source: https://onco.cc/targets/znrf3/  
OnCo record `znrf3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

ZNRF3 (E3 ubiquitin-protein ligase ZNRF3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Adrenocortical carcinoma.

## Summary

E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signalling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signalling pathway. Acts as a tumour suppressor in the intestinal stem cell zone by inhibiting the Wnt signalling pathway, thereby restricting the size of the intestinal stem cell zone.

Open Targets scores its association with cancer at 0.55 (direct and indirect evidence; datatypes affected pathway 0.61, literature 0.94, genetic association 0.56, somatic mutation 0.47, animal model 0.41). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Adrenocortical Carcinoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: zinc and ring finger 3; E3 ubiquitin-protein ligase ZNRF3; KIAA1133; BK747E2.3; FLJ22057; RNF203
- Tags: cancer-genes-wave
- Symbol: ZNRF3
- Class: tumor-suppressor
- Biology: E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signalling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signalling pathway. Acts as a tumour suppressor in the intestinal stem cell zone by inhibiting the Wnt signalling pathway, thereby restricting the size of the intestinal stem cell zone. Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification. Location: Cell membrane (UniProt). Locus 22q12.1 (HGNC).
- Where found: Adrenocortical carcinoma: IntOGen driver in 1 cohort (ACC)

## 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 a loss-of-function (LoF) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:18126: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18126
- UniProt Q9ULT6: https://www.uniprot.org/uniprotkb/Q9ULT6/entry
- NCBI Gene 84133: https://www.ncbi.nlm.nih.gov/gene/84133
- Ensembl ENSG00000183579: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000183579

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Adrenocortical carcinoma](https://onco.cc/cancers/adrenocortical/)

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JSON: https://onco.cc/api/v1/entities/znrf3.json