TRPC5 Gene: Function, Expression, and Clinical Significance

TRPC5 encodes a member of the transient receptor potential (TRP) family of ion channels, specifically the canonical subfamily C. The protein forms a calcium-permeable, non-selective cation channel that is activated by G-protein-coupled receptors and receptor tyrosine kinases. TRPC5 is highly expressed in the brain, particularly in the hippocampus and cortex, and plays critical roles in neuronal excitability, neurite outgrowth, and fear-related behavior. It is also expressed in kidney podocytes, where it contributes to calcium signaling and cytoskeletal dynamics. Dysregulation of TRPC5 has been implicated in pain perception, anxiety disorders, and focal segmental glomerulosclerosis (FSGS).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Calcium signaling pathway (KEGG: hsa04020)

• Phospholipase C-activating G-protein coupled receptor pathway

• TRP channel regulation (Reactome: R-HSA-3295580)

The TRPC5 protein (UniProt Q9NZY4) is a 975-amino acid multi-pass membrane protein that assembles as a homotetramer or heterotetramer with other TRPC family members. It contains ankyrin repeats in the N-terminal region, a pore-forming loop, and a C-terminal calmodulin-binding domain. The channel is activated downstream of phospholipase C (PLC) signaling, leading to calcium and sodium influx. TRPC5 is regulated by phosphatidylinositol 4,5-bisphosphate (PIP2), calmodulin, and nitric oxide. Its activity modulates neuronal growth cone guidance, dendritic spine morphology, and podocyte foot process integrity.