AMER1

Overview

AMER1 (also known as FAM123B and WTX) is an X-linked negative regulator of the WNT/beta-catenin signaling pathway. It promotes beta-catenin degradation by facilitating the destruction complex. In colorectal cancer, AMER1 is recurrently inactivated through loss-of-function mutations, functioning as an alternative mechanism of Wnt pathway activation alongside APC mutations. Because it is X-linked, hemizygous mutations are sufficient to cause loss of function in male patients, and females may lose the second allele through X-inactivation or somatic deletion.

Alterations observed in the corpus

  • AMER1 is recurrently mutated in colorectal adenocarcinoma across 276 TCGA CRC tumors; virtually all mutations detected were loss-of-function (frameshift or nonsense), consistent with its role as an X-linked negative regulator of the WNT pathway PMID:22810696
  • Mutated in TCGA lung squamous cell carcinoma cohort (178 tumors), identified as part of broad genomic characterization PMID:22960745
  • Recurrently mutated in non-hypermutated CRC (concordant between primary and metastasis per Figure 1B) PMID:25164765

Cancer types (linked)

  • COAD (colorectal adenocarcinoma): Recurrent loss-of-function mutations across 276 TCGA tumors; functions as an alternative WNT pathway inactivation mechanism PMID:22810696

Co-occurrence and mutual exclusivity

  • AMER1 loss-of-function mutations occur in CRC tumors as an alternative to APC inactivation, both converging on aberrant WNT/beta-catenin activation PMID:22810696

Therapeutic relevance

  • No direct targeted therapy; inactivation contributes to WNT pathway dysregulation, potentially relevant to emerging WNT inhibitor strategies in CRC PMID:22810696

Open questions

  • The relative frequency and mutual exclusivity of AMER1 vs. APC mutations across CRC subtypes warrants further characterization.

Sources

  • PMID:22810696 — TCGA CRC comprehensive molecular characterization (276 tumors)

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