TRPC6 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, OMIM

TRPC6 encodes a member of the transient receptor potential (TRP) family of cation channels, specifically the canonical subfamily C. The protein forms a non-selective calcium-permeable cation channel that is activated by diacylglycerol (DAG) and is involved in receptor-operated calcium entry. TRPC6 is widely expressed in kidney podocytes, vascular smooth muscle, lung, and heart, playing critical roles in glomerular filtration barrier integrity, vascular tone regulation, and cardiac hypertrophy signaling. Mutations in TRPC6 cause autosomal dominant focal segmental glomerulosclerosis (FSGS) and are associated with pulmonary arterial hypertension.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Calcium signaling pathway (KEGG: hsa04020)

• cGMP-PKG signaling pathway (KEGG: hsa04022)

• Vascular smooth muscle contraction (KEGG: hsa04270)

• NFAT signaling in cardiac hypertrophy (Reactome: R-HSA-5576891)

The TRPC6 protein (UniProt Q9Y210) is a 931-amino acid multi-pass membrane protein with six transmembrane domains, forming a cation channel that is permeable to Ca2+ and Na+. It contains ankyrin repeats in the N-terminal cytoplasmic region and a conserved TRP domain. The channel is activated by diacylglycerol (DAG) in a protein kinase C-independent manner and is modulated by phosphorylation, PIP2, and interactions with other TRPC proteins. In podocytes, TRPC6 localizes to the slit diaphragm and regulates calcium-dependent signaling critical for cytoskeletal dynamics. Pathogenic mutations cluster in the transmembrane and C-terminal domains, enhancing channel activity.