Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling
Anagha Krishna; Alison Meynert; Karamjit Singh Dolt; Martijn Kelder; Agavni Mesropian; Ailith Ewing; Conny Brouwers; Jill Claassens · 2026 · Nature Genetics
WASTE classifies this as Negative / Null Result Report · AI classification, approximate
The study found no significant effect — useful as a negative control or null benchmark for your own design.
Abstract
CTNNB1, the gene encoding β-catenin, is a frequent target for oncogenic mutations activating the canonical Wnt signaling pathway, typically through missense mutations within a degron hotspot motif in exon 3. Here, we combine saturation genome editing with a fluorescent reporter assay to quantify signaling phenotypes for all 342 possible missense mutations in the mutation hotspot. Our data define the genetic requirements for β-catenin degron function, refine the consensus motif for substrate recognition by β-TRCP and reveal diverse levels of signal activation among known driver mutations. Tumor
Abstract by Anagha Krishna; Alison Meynert; Karamjit Singh Dolt; Martijn Kelder; Agavni Mesropian; Ailith Ewing; Conny Brouwers; Jill Claassens, Nature Genetics (2026) — licensed CC BY 4.0.
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Metadata source: OpenAlex · DOI 10.1038/s41588-025-02496-5