AMER1 (WTX) gene on the X chromosome

AMER1 is located on the X chromosome at Xq11.1. It is altered in 15% to 20% of Wilms tumor cases.[3,4,13,37,38] Germline pathogenic variants in AMER1 cause an X-linked sclerosing bone dysplasia, osteopathia striata congenita with cranial sclerosis (MIM300373).[39] Despite having germline AMER1 pathogenic variants, individuals with osteopathia striata congenita are not predisposed to tumor development.[39] The AMER1 protein appears to be involved in both the degradation of beta-catenin and in the intracellular distribution of APC protein.[36,40] AMER1 is most commonly altered by deletions involving part or all of the AMER1 gene, with deleterious single nucleotide variants occurring less commonly.[3,13,37] Most Wilms tumor cases with AMER1 alterations have epigenetic 11p15 abnormalities.[13]

AMER1 alterations are equally distributed between males and females, and AMER1 inactivation has no apparent effect on clinical presentation or prognosis.[3]