STRADA Gene: Function, Mutations, and Associated Diseases (PMSE)

The STRADA gene encodes the STE20-related kinase adaptor alpha protein, a pseudokinase that forms a heterotrimeric complex with STK11 (LKB1) and MO25 (CAB39). This complex is essential for the activation and cytoplasmic localization of LKB1, which in turn phosphorylates and activates AMPK and other AMPK-related kinases. STRADA functions as a key regulator of cellular energy homeostasis, cell polarity, and growth control via the AMPK-mTOR signaling axis. Loss-of-function mutations in STRADA cause polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• AMPK signaling pathway (KEGG: hsa04152)

• mTOR signaling pathway (KEGG: hsa04150)

• LKB1 signaling events (Reactome: R-HSA-5628897)

STRADA (STE20-related kinase adaptor alpha) is a 431-amino acid pseudokinase that lacks catalytic activity but serves as a critical scaffold. It binds directly to STK11 (LKB1) and MO25 (CAB39) to form a stable heterotrimeric complex. This complex is required for LKB1 to exit the nucleus and become fully active in the cytoplasm. Active LKB1 then phosphorylates AMPK and 13 other AMPK-related kinases, regulating cell metabolism, polarity, and growth. STRADA contains a STE20-like kinase domain but has substitutions in key catalytic residues, rendering it inactive. Its N-terminal region mediates LKB1 binding, while the C-terminal region interacts with MO25. Mutations in STRADA that disrupt complex formation or stability lead to PMSE syndrome.