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Symbol TRPC3 contributors: mct/pgu - updated : 28-08-2020
HGNC name transient receptor potential cation channel, subfamily C, member 3
HGNC id 12335
Corresponding disease
SCA41 spinocerebellar ataxia 41
Location 4q27      Physical location : 122.800.182 - 122.872.909
Synonym name short transient receptor potential channel 3
Synonym symbol(s) TRP3
TYPE functioning gene
STRUCTURE 72.70 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 - 8401 105.4 921 - 2005 15728370
  • isoform a
  • 11 - 3330 97.2 848 - 2005 15728370
  • isoform b
  • 11 - 8317 - 893 - 2005 15728370
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartventricle  highly Homo sapiens
    Digestiveintestinelarge intestinecolon lowly
    Hearing/Equilibriumearinnercochlea highly Homo sapiens
    Nervousbrainhindbraincerebellum predominantly Homo sapiensFetal
     brainhindbraincerebellum   Homo sapiensAdult
     gangliasensory ganglia  lowly Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumcochlea cell Homo sapiens
    Hearing / Equilibriumhair cell receptor Homo sapiens
    Muscularmyocyte Homo sapiensAdult
    NervousPurkinje cell Homo sapiens
    cell lineage
    cell lines megakaryocytes
    fluid/secretion sperm
    at STAGE
  • cytoplasmic N terminus with ankyrin repeats and a coiled-coil structure, and the ankyrin repeat (AR) region (38-188 amino acids) forms extracellular Ca(2+)-entry channels by homo or heteromerization with other TRP subtypes in various cells including skeletal myotubes
  • six transmembrane segments
  • a cytoplasmic C terminus with a dystrophin (coiled-coil) domain and a highly conserved TRP (EWKFHR) domain
  • secondary structure
  • has four elbow-like membrane reentrant helices prior to the first transmembrane helix, and the third transmembrane helix S3 is remarkably long, shaping a unique transmembrane domain, and constituting an extracellular domain that may serve as a sensor of external stimuli
    interspecies homolog to murine Trpc3 (96.4pc)
    homolog to rattus Trpc3 (95.9pc)
  • transient receptor family
  • STrpC subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
  • colocalizing with TRPC4
  • mostly associated to the surface of the spermatogenic cells
  • a fraction of canonical transient receptor potential 3 (TRPC3) channels is localized to mitochondria
  • basic FUNCTION
  • receptor-activated non-selective calcium premeant cation channel
  • behaving in embryonic kidney as an inositol phosphate and diacylglycerol-gated channel
  • may influence sperm motility
  • mediating T-cell receptor-dependent calcium entry in human T- lymphocytes
  • required for BDNF-mediated neuronal protection and protects cerebellar granule neurons against serum deprivation-induced cell death
  • additional function of TRPC3, and TRPC7 may be to enhance secretion either by affecting transport through the Golgi stack or by increasing fusion at the plasma membrane
  • playing an essential role for angiotensin II-induced cardiac hypertrophy
  • regulating agonist-stimulated Ca2+ mobilization by selectively mediating interaction between ORAI1 and GNB2L1
  • necessary mediator of pathologic cardiac hypertrophy, in part through a calcineurin/NFAT signaling pathway
  • TRPC3 channels have likely important physiological functions in the fully developed cerebellum
  • is involved in adult cerebellar function
  • TRPC3-dependent currents may differ significantly in their regulation from those overexpressed in expression systems
  • a subtle activation/inhibition of voltage-independent Ca2+ channels like TRPC3 could play a crucial role in Ca2+ homeostasis and consequently in regulation of electromechanical activity of the developing heart
  • TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes
  • regulate cardiac fibroblast proliferation and differentiation, likely by controlling the Ca(2+) influx that activates extracellular signal-regulated kinase signaling
  • likely plays an important role in atrial fibrillation by promoting fibroblast pathophysiology
  • TRPC3 channels contribute to mitochondrial Ca(2+) uptake
  • role of TRPC3 and Ca(2+) influx in the regulation of BDNF secretion by human airway smooth muscle and the enhancing effects of inflammation
  • heteromeric TRPC3/TRPC1 could participate in regulating the resting cytosolic Ca(2+) levels in skeletal muscle
  • display unique gating and regulatory properties that allow for recognition and integration of multiple input stimuli including lipid mediators, cellular Ca(2+) gradients, as well as redox signals
  • obligatory requirement for a member of the TRPC family of cation channels in ER stress-induced apoptosis in macrophages, underscoring a rather selective role of the TRPC3 channel on mechanisms related to the UPR signaling in M1 macrophage
  • combines functions of an unspecific ion channel and a signal transducer
  • regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFKB1 pathway
  • role of TRPC3 channel in endoplasmic reticulum stress-induced apoptosis of human coronary artery endothelial cells
  • is a cation channel that permeates both Ca(2+) and Na(+)
  • regulates the automaticity of embryonic stem cell-derived cardiomyocytes
  • is a major contributor to the cellular heterogeneity that introduces distinct physiological properties in Purkinje cells, conjuring functional heterogeneity in cerebellar sensorimotor integration
  • CELLULAR PROCESS cell migration & motility
    a component comprised of homo- or heterotetramers between TRPC3/6/7
    small molecule
  • TRPC1, ITPR3, MX1, RNF24
  • PLCG1
  • interacting with TRPM4 (negatively modulated the channel activity of TRPC3 via the interaction between the two channel proteins)
  • interacting with RYR1 (TRPC3 and RYR1 are functionally engaged via linker proteins in skeletal muscle)
  • TRPC3 TRP domain and AMP-activated protein kinase binding site are required for TRPC3 activation by erythropoietin
  • TRPC3 channel activation dependent on ADORA1 activation and playing a predominant role in arrhythmogenesis
  • SYPL2 could be a new factor for regulating Ca(2+) transients during skeletal muscle contraction possibly via a correlation with TRPC3 and TRPC4
  • interaction between SYPL2 and TRPC3 participates in regulating Ca(2+) transients in skeletal muscle
  • coupling between TRPC3 and the SLC8A1 transporter contributed to VEGFA-induced ERK1/2 activation and angiogenesis in primary endothelial cells
  • located in mitochondria, regulates mitochondrial calcium and reactive oxygen species(ROS) production
  • cell & other
    activated by diacylglycerol (DAG) generated by G protein-coupled receptors (GPCR)/Gαq/phospholipase C signaling
    N-linked protein glycosylation
    EPO, in a modulated manner by TRPC6
    ITPR with bound IP3
    Phosphorylated by PRKG1 at two distinct residues, Thr-11 and Ser-263 and PRKG1-dependent phosphorylation of TRPC3 was reduced in TRPC3 channels in which either Thr-11 or Ser-263 had been mutated
    Other may be activated by Ca2+ store depletion
    is probably operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors
    corresponding disease(s) SCA41
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    enhanced expression in type 2 diabete mellitus patients
    constitutional       loss of function
    TRPC3 deficiency inhibited high salt-induced cardiac hypertrophy
    Variant & Polymorphism
    Candidate gene
  • as an emerging candidate protein implicated in various forms of ataxia in humans
  • Marker
    Therapy target
    cardiovascularaquiredheart failure
    pharmacologic inhibitors of TRPC channels might be a strategy for attenuating local Ca2+ signals involved in pathologic cardiac hypertrophy or failure
    TRPC3 represents a promising target to prevent conduction disturbances
    cardiovascularaquiredheart failure
    may represent a novel target for preventing high salt-induced cardiac damage
    TRPC3 might be a promising target for autosomal dominant polycystic kidney disease (ADPKD) treatment
  • gain-of-function mutation (T635A) in the transient receptor potential (TRP) channel Trpc3 results in abnormal channel gating and causes cerebellar ataxia in the dominant Moonwalker (Mwk) mouse mutant (
  • double Trpc3/Trpc6 knock-out mice showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds