AGAP2 Gene: Function, Mutations, and Disease Associations

AGAP2 (ArfGAP With GTPase Domain, Ankyrin Repeat And PH Domain 2) encodes a multidomain protein that functions as both a GTPase-activating protein (GAP) for Arf family small GTPases and a GTPase itself. The protein contains an N-terminal GTPase domain, a central ArfGAP domain, an ankyrin repeat region, and a pleckstrin homology (PH) domain. AGAP2 is involved in cell signaling, cytoskeletal dynamics, and vesicle trafficking. It is highly expressed in the brain and has been implicated in neuronal development, synaptic function, and cancer progression, particularly in glioblastoma and other malignancies.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• PI3K-Akt signaling pathway (Reactome: R-HSA-1257604)

• Arf family GTPase cycle (Reactome: R-HSA-9007101)

• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006934)

The AGAP2 protein (also known as PIKE) is a 998-amino acid multidomain protein that integrates GTPase and ArfGAP activities. It localizes to the cytoplasm and plasma membrane, where it interacts with phosphoinositides via its PH domain. AGAP2 acts as a scaffold linking receptor tyrosine kinases to PI3K activation, thereby promoting cell growth and survival. In the nervous system, it regulates dendritic spine morphology and synaptic plasticity. Aberrant AGAP2 expression or mutation contributes to oncogenesis and neurodevelopmental disorders.