Amer3, also known as FAM123C, is a member of the APC membrane recruitment family of APC-binding proteins. It acts as a positive regulator of the Wnt-β-catenin signalling pathway, differentiating it from other family members Amer1 and Amer2 which are negative regulators [3]. The Amer gene family, including Amer3, is vertebrate-specific and may have played an important role in vertebrate evolution [4]. Its expression has been detected in the central and peripheral nervous systems, as well as in other tissues such as the retina, inner ear, and nasal epithelium during mouse embryonic development [6].

In human studies, certain variants of the AMER3 gene modify the U-shaped association of urinary total hydroxyphenanthrene with fasting plasma glucose, indicating a gene-environment interaction. Specifically, two common variants (rs72854995 and rs72854999) interact with urinary total hydroxyphenanthrene on fasting plasma glucose change [1]. Also, the methylation of the AMER3 gene mediates the negative association between urinary polycyclic aromatic hydrocarbon metabolites and fasting plasma glucose in non-smokers, providing a new clue for the development of hypoglycemic agents [2]. Moreover, AMER3 has been identified as a plausible candidate gene in the etiology of esophageal atresia/tracheoesophageal fistula through exome sequencing [5].

In conclusion, Amer3 is a key positive regulator of the Wnt-β-catenin signalling pathway. Its study through human-based research has revealed its significance in gene-environment interactions related to fasting plasma glucose and its potential role in the development of esophageal atresia/tracheoesophageal fistula. Understanding Amer3's functions contributes to a better understanding of these biological processes and disease conditions.