Submission Details

Autosomal dominant

05/22/2020

The PPP1R12A gene is located on chromosome 12 at 12q21.2-q21.31 and encodes protein phosphatase 1 regulatory subunit 12A. This protein forms part of myosin phosphatase, an enzyme that plays an important regulatory role in cell morphology and motility. PPP1R12A was first reported in relation to autosomal dominant genitourinary and/or brain malformation syndrome in 2020 (31883643: Hughes et al. 2020). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Twelve unique variants, all of which were predicted null, have been reported in humans (31883643: Hughes et al. 2020). In the majority of cases, the variants were shown to have occurred de novo. The mechanism for disease is haploinsufficiency. This gene-disease relationship is supported by expression in the brain and urogenital system during embryonic development (31883643: Hughes et al. 2020) and overlapping phenotypes observed in C. elegans (10208747: Wissman et al. 1999), Drosophila (12505998: Tan et al. 2003), and zebrafish models (19515695: Weiser et al. 2009). In summary, there is strong evidence to support the relationship between PPP1R12A and autosomal dominant genitourinary and/or brain malformation syndrome. Additional reports in humans published at least three years from the first proposal of the association are needed to reach a definitive classification.

31883643 12505998 10208747 19515695