Molecular characteristics

The ALPK3 gene is located at 15q25.3 and encodes alpha-protein kinase 3, a nuclear kinase that plays an essential role in early differentiation of cardiomyocytes. Alpha-protein kinase 3 participates in normal intercalated disc formation and sarcomere organization. However, the exact function of this protein remains incompletely understood.

The majority of disease-causing ALPK3 variants described to date consist of truncating variants, including nonsense, frameshift and splice site variants. At least one patient had a complete gene deletion and a truncating variant (unpublished). Therefore, it is hypothesized that ALPK3 variants lead to loss of function of the encoded protein.