AMER1

Chr XXLD

APC membrane recruitment protein 1

NCBI Gene: 139285 ENSG00000184675 UniProt: Q5JTC6 OMIM: 300647

The AMER1 protein regulates canonical Wnt signaling by binding phosphatidylinositol 4,5-bisphosphate and interacting with components of the beta-catenin destruction complex. Mutations cause osteopathia striata with cranial sclerosis, a skeletal dysplasia with X-linked dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.37).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Regulator of the canonical Wnt signaling pathway. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex. Acts both as a positive and negative regulator of the Wnt signaling pathway, depending on the context: acts as a positive regulator by promoting LRP6 phosphorylation. Also acts as a negative regulator by acting as a scaffold protein for the beta-catenin destruction complex and promoting stabilization of Axin at the cell membrane. Promotes CTNNB1 ubiquitination and degradation. Involved in kidney development

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Osteopathia striata with cranial sclerosisMIM #300373

XLD

Clinical highlights

Gene-disease validity (ClinGen)

osteopathia striata with cranial sclerosis · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.37

LOEUF

LOF

Mechanism· G2P

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GeneReview available — AMER1