SASH3 Gene - SAM and SH3 Domain Containing 3 | Function, Mutations & Disease

SASH3 (SAM and SH3 domain containing 3) is a protein-coding gene located on the X chromosome. It encodes a scaffold protein containing both SAM (sterile alpha motif) and SH3 (Src homology 3) domains, which are involved in protein-protein interactions and signal transduction. SASH3 is predominantly expressed in lymphoid tissues and plays a critical role in immune cell signaling, particularly in T-cell activation and proliferation. It is also implicated as a putative tumor suppressor in various cancers, including breast cancer and lymphoma.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• T-cell receptor signaling pathway (Reactome: R-HSA-202403)

• PI3K/AKT signaling (Reactome: R-HSA-1257604)

• Apoptosis (Reactome: R-HSA-109581)

SASH3 is a 644-amino acid scaffold protein with an N-terminal SAM domain and a C-terminal SH3 domain. It localizes to the cytoplasm and is involved in signal transduction, particularly in T-cells. The SAM domain mediates oligomerization and protein interactions, while the SH3 domain binds proline-rich motifs. SASH3 acts as a tumor suppressor by modulating PI3K/AKT and MAPK pathways, and its loss correlates with poor prognosis in breast cancer and lymphoma.