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Symbol TRPC6 contributors: mct/shn/pgu - updated : 22-05-2024
HGNC name transient receptor potential cation channel, subfamily C, member 6
HGNC id 12338
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumearinnercochlea   Homo sapiens
Nervousbrain   moderately Homo sapiens
 brainlimbic systemhippocampus   Homo sapiens
 gangliasensory ganglia    Homo sapiens
Respiratorylung   predominantly Homo sapiens
Urinarykidneytubule    Homo sapiens
 kidneynephron    Homo sapiens
 kidneynephronrenal capsuleglomerulus  Homo sapiens
SystemCellPubmedSpeciesStageRna symbol
Hearing / Equilibriumcochlea cell Homo sapiens
Hearing / Equilibriumhair cell receptor Homo sapiens
Urinarymesangial cell Homo sapiens
Urinarypodocyte Homo sapiens
Urinarytubular cell Homo sapiens
cell lineage
cell lines
fluid/secretion sperm
physiological period embryo
Text kidney
  • cytoplasmic N terminus with four ankyrin repeats
  • a coiled-coil structure
  • six transmembrane segments
  • a cytoplasmic C terminus with a dystrophin (coiled-coil) domain
  • a highly conserved TRP (EWKFHR) domain
  • conjugated GlycoP , PhosphoP
    interspecies ortholog to Drosophila store-operated calcium channel (Soc)
    ortholog to Trpc6, Mus musculus
    ortholog to Trpc6 , Rattus norvegicus
    ortholog to trpc6, Danio rerio
    ortholog to TRPC6, Pan troglodytes
  • Ca2+ conductive channel in TRPC family
  • DAG-activated subfamily of channels
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
  • mostly associated to the surface of the spermatogenic cells
  • localized to excitatory synapses
  • translocates to the plasma membrane upon stimulation and remains there as long as the stimulus is present
  • basic FUNCTION
  • non selective cation channel enabling Ca2+ influx into cells
  • supposed to have a fundamental role in the regulation of smooth muscle tone in blood vessels and lung (
  • may influence sperm motility
  • calcium (Ca2+) and magnesium (Mg2+) conducting channel, during proliferation of human osteoblasts
  • its activation is sufficient to induce keratinocyte differentiation similar to the physiological stimulus [Ca2+]
  • playing an essential role for proper regulation of podocyte structure and function, by its channel activity at the slit diaphragm
  • Ca2+-permeable channel, activation of which is linked to a G protein-coupled receptor or receptor tyrosine kinase signaling pathway
  • playing a unique and indispensable role in acute hypoxic pulmonary vasoconstriction
  • required for BDNF-mediated neuronal protection and protects cerebellar granule neurons against serum deprivation
  • might act as an important mediator for sensing the extracellular signals that affect synaptic and behavioral plasticity
  • involvement of TRPC6-mediated Ca2+ entry in the RHOA-dependent regulation of actin cytoskeleton has been demonstrated in endothelial cells and kidney podocytes
  • playing an essential role for angiotensin II-induced cardiac hypertrophy
  • contributes to the Ca(2+) leak of human erythrocytes
  • promotes hippocampal neuron dendritic growth
  • regulates TRPC3 activation by erythropoietin by modulation of signaling mechanisms, including reduced interaction of TRPC6 with phospholipase C gamma and Epo-R
  • may be involved in VEGF-mediated angiogenesis
  • participates both in cacapitative Ca2+ entry and non capacitative Ca2+ entry through its interaction with the Orai-STIM1 complex or TRPC3 respectively
  • invovled in the development of gastric cancers through the regulation of Ca2+ elevation which is essential for G2/M transition
  • necessary mediator of pathologic cardiac hypertrophy, in part through a calcineurin/NFAT signaling pathway
  • TRPC5 and TRPC6 are antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes
  • TRPC5 and TRPC6 channels are now known as the Ca(2+) influx pathways for nonselective, cationic current in podocytes
  • upregulation of TRPC6 is involved in the Ca2+ signaling and actin assembly in human mesangial cells (MCs) after chronic hypoxia
  • role of TRPC6 in actin assembly and reorganization in response to chronic hypoxia
  • TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes
  • dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis
  • is the endothelial calcium channel that regulates leukocyte transendothelial migration during the inflammatory response
  • TRPC6 channel translocation into phagosomal membrane augments phagosomal function
  • may protect renal ischemia-reperfusion injury through inhibiting necroptosis of renal tubular epithelial cells
  • is emerging as a functional element for the control of calcium currents in immune-committed cells and target tissues
  • is important in glomerular epithelial cells or podocytes for the process of glomerular filtration
  • TRPC6 plays a crucial role in the development of kidney injuries by inducing podocyte injury, maybe via its role in the immune system
  • CELLULAR PROCESS cell migration & motility
    text regulation of intracellular calcium concentration
    a component comprised of homo- or heterotetramers between TRPC3/6/7
    small molecule
  • TRPC3 and TRPC7 (
  • transient receptor potential channel 2, TRPC2 (
  • SH2 domain of Fyn (
  • myxovirus (influenza) resistance A, MxA (
  • ORAI calcium release-activated calcium modulator 1, ORAI1 (
  • promoted dendritic growth via the CAMK4-CREB pathway
  • is in a molecular complex with RhoA
  • phospholipase C (PLC)-gamma1 and cytoplasmic domain of nephrin (
  • insulin increases generation of ROS in part through activation of NADPH oxidases, and this step contributes to modulation of podocyte TRPC6 channels
  • PI3K/PTEN pathway plays an important role in the translocation of TRPC6 to the plasma membrane and may thus have a significant impact on Ca2+ signaling in cells that endogenously express TRPC6
  • SNF8 interacts with TRPC6, binding to the amino-terminal cytoplasmic domain of the channel
  • TRPC6 down-regulation could contribute to the antiproteinuric effect of vitamin D
  • involvement of three basic residues in the integrative overlapping binding site for S100A1 on the C tail of TRPC6
  • function of NOD2 for the regulation of TRPC6 channels, suggesting that TRPC6-dependent Ca(2+) signaling is one of the critical signal transduction pathways that links innate immunity mediator NOD2 to podocyte injury
  • PRKG1 is a potent negative modulator of cardiac systolic mechanosignaling that requires TRPC6 as the target effector
  • redundant role of PLCE1-mediated TRPC6 activation at least in podocytes
  • locally generated SDC4 may play a role in regulating TRPC6 channels, and may contribute to glomerular pathology
  • evidence for a role of immunophilins, including FKBP3 and FKBP8, in Non-capacitative calcium entry (NCCE) mediated by TRPC6
  • lysophosphatidylcholine (lysoPC) induces CALM1 phosphorylation at Tyr(99) by a Src family kinase and phosphorylated CALM1 activates PI3K to produce PIP3, which promotes TRPC6 translocation to the cell membrane
  • lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical TRPC6 channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation
  • cell & other
    activated by diacylglycerol (DAG) generated by G protein-coupled receptors (GPCR)/Gαq/phospholipase C signaling
    N-linked protein glycosylation
    receptor tyrosine kinases or G protein-coupled receptors
    cysteine oxidation-dependent pathway which not only stimulates the TRPC6 channel by itself but also sensitizes the channels to diacylglycerol and promotes TRPC6 trafficking to the cell surface
    PLC-gamma1 and nephrin (
    diacylglycerol (
    induced by insulin that increases the expression of TRPC6 channels in podocytes by activation of the calcineurin-dependent pathway
    Phosphorylated by Src family PTKs (
    Other seems to be non-activated by calcium store depletion, independently of protein kinases C
    probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinase
  • PI3K/PTEN pathway plays an important role in TRPC6 activation
    corresponding disease(s) FSGS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    upregulated in gastric cancer epithelial cells
    constitutional       gain of function
    is involved in Ca(2+) signaling and actin reorganization in podocytes after oxygen glucose deprivation (OGD)
  • to idiopathic membranous glomerulopathy (iMN)
  • Variant & Polymorphism SNP
  • a SNP in the promoter region and a missense variant in exon 4 may be putative causal variants for infantile hypertrophic pyloric stenosis
  • 254C->G SNP may predispose individuals to an increased risk of idiopathic pulmonary arterial hypertension
  • genetic variants in TRPC6 might affect susceptibility to development or progression of iMN
  • Candidate gene
    Therapy target
    newly-identified ROS/TRPC6 pathway will pave the way to new, promising therapeutic strategies to target kidney diseases such as diabetic nephropathy
    manipulation of TRPC6 function may thus offer a therapeutic strategy for the control of pulmonary hemodynamics and gas exchange
    activation by hyperforin may represent a new innovative therapeutic strategy in skin disorders characterized by altered keratinocyte differentiation
    key mediator of tumor growth of glioblastoma multiforme (GBM) and may be a promising therapeutic target in the treatment of GBM
    cardiovascularaquiredheart failure
    . pharmacologic inhibitors of TRPC channels might be a strategy for attenuating local Ca2+ signals involved in pathologic cardiac hypertrophy or failure
    TRPC6 channel is a good target for developing novel treatment for pulmonary arterial hypertension (PAH), and BI-749327, a selective TRPC6 blocker, is potentially a novel and effective drug for treating PAH
    TRPC6 might aggravate SARS COV-2 induced inflammation and could be a target for inhibiting drugs
  • in TRPC6-/- mice, a higher contractility in isolated tracheal and aortic rings was observed following application of the agonists methacholine and phenylephrine, respectively, as well as a reduced agonist-induced expiration rate (