TRPC6 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

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target has curated data in GtoImmuPdb

Target id: 491

Nomenclature: TRPC6

Family: Transient Receptor Potential channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 931 11q21-q22 TRPC6 transient receptor potential cation channel subfamily C member 6 12
Mouse 6 1 930 9 A1 Trpc6 transient receptor potential cation channel, subfamily C, member 6 3
Rat 6 1 930 8q11 Trpc6 transient receptor potential cation channel, subfamily C, member 6 29
Previous and Unofficial Names
TRP6 [15] | short transient receptor potential channel 6 | transient receptor potential cation channel
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
TRPC4 38
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
calmodulin 2,4,9
FKBP prolyl isomerase 1A 39
SNF8 5
Functional Characteristics
γ = 28-37 pS; conducts mono and divalent cations with a preference for divalents (PCa/PNa = 4.5–5.0); monovalent cation current suppressed by extracellular Ca2+ and Mg2+, dual rectification (inward and outward), or inward rectification
Ion Selectivity and Conductance
Species:  Human
Rank order:  Ca2+ > Cs+ > Na+
References:  12
Ion Selectivity and Conductance Comments
Slope conductance of 35pS in symmetrical 120mM Cs+ [12].
Chemical activators (Human)
Physical activators (Human)
Membrane stretch

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
OAG Hs Agonist - - 1x10-4 -60.0 12
Conc range: 1x10-4 M [12]
Holding voltage: -60.0 mV
SLG Hs Agonist - - 1x10-4 -60.0 12
Conc range: 1x10-4 M [12]
Holding voltage: -60.0 mV
SAG Hs Agonist - - 1x10-5 -60.0 12
Conc range: 1x10-5 M [12]
Holding voltage: -60.0 mV
pyrazolopyrimidine 4n Hs Activation 5.9 pEC50 - - 23
pEC50 5.9 (EC50 1.39x10-6 M) [23]
GSK1702934A Hs Agonist 6.4 pIC50 - - 36
pIC50 6.4 (IC50 4.4x10-7 M) [36]
Description: Activation of TRPC6-mediated currents in HEK293 cells in whole-cell patch-clamp experiments.
arachidonic acid Hs - - - - -
lysophosphatidylcholine Hs - - - - -
hyperforin Hs - - - - - 18
hyp 9 Hs - - - - - 17
20-HETE Hs - - - - -
flufenamate Hs - - - - -
Activator Comments
The naturally occurring plant compound hyperforin has been identified as a selective activator of the mouse TRPC6 channel [10].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
GSK2833503A Hs - 8.5 pIC50 - 80.0 28
pIC50 8.5 (IC50 3x10-9 M) [28]
Holding voltage: 80.0 mV
Description: Measuring whole-cell current by patch-clamp in HEK cells expressing hTRPC6 with cation flux activated by OAG.
SAR7334 Hs - 8.0 pIC50 - - 19
pIC50 8.0 (IC50 9.5x10-9 M) [19]
SH045 Hs - 7.2 pIC50 - - 13
pIC50 7.2 (IC50 6.3x10-8 M) [13]
Description: Measuring inhibition of calcium flux in HEK293 cells expressing hTRPC6, in a FLIPR assay.
larixyl acetate Hs Inhibition 7.0 pIC50 - - 31
pIC50 7.0 (IC50 1x10-7 M) [31]
GSK417651A Hs Antagonist 6.4 pIC50 - - 32
pIC50 6.4 (IC50 4.4x10-7 M) [32]
Description: Inhibition of recombinant hTRPC6-mediated, carbachol-stimulated Ca2+/Na+ influx in HEK293-MSRII cells assessed by FLIPR assay.
clemizole Hs - 5.9 pIC50 - - 26
pIC50 5.9 [26]
Gd3+ Mm Antagonist 5.7 pIC50 - -60.0 15
pIC50 5.7 (IC50 1.9x10-6 M) [15]
Holding voltage: -60.0 mV
La3+ Mm Antagonist 5.4 pIC50 - -60.0 15
pIC50 5.4 [15]
Holding voltage: -60.0 mV
SKF96365 Mm Antagonist 5.4 pIC50 - -60.0 15
pIC50 5.4 (IC50 4.2x10-6 M) [15]
Holding voltage: -60.0 mV
norgestimate Hs - 5.3 pIC50 - - 20
pIC50 5.3 (IC50 5.2x10-6 M) [20]
Description: Norgestimate-induced inhibition of hTRPC6-mediated Ca2+ entry in transfected HEK-FITR cells stimulated with the OAG diacylglycerol analog.
La3+ Hs - ~5.2 pIC50 - -
pIC50 ~5.2 (IC50 ~6x10-6 M)
amiloride Mm Antagonist 3.9 pIC50 - -60.0 15
pIC50 3.9 (IC50 1.29x10-4 M) [15]
Holding voltage: -60.0 mV
Cd2+ Mm Antagonist 3.6 pIC50 - -60.0 15
pIC50 3.6 (IC50 2.53x10-4 M) [15]
Holding voltage: -60.0 mV
Extracellular H+ Hs - - - - -
2-APB Hs - - - - -
ACAA Hs - - - - -
GsMTx-4 Hs - - - - -
KB-R7943 Hs - - - - -
ML9 Hs - - - - -
View species-specific channel blocker tables
Channel Blocker Comments
Data from a meeting abstract suggest that GSK2293017A is a TRPC6 inhibitor (pIC50: ~8.00), but the chemical structure has not been conclusively disclosed [36].
Immunopharmacology Comments
Expressed on rodent B and T cells, rodent and human neutrophils and human monocytes/macrophages [22].
Tissue Distribution
Heart, lung, kidney, muscle, intestine, stomach, pancreas, prostate, bone, brain.
Species:  Human
Technique:  RT-PCR
References:  25
Testis, lung spleen, epididymis, ovary, brain , retina, iris, heart, kidney and liver.
Species:  Mouse
Technique:  RT-PCR, western blot and immunohistochemistry.
References:  14,16,30
Brain, kidney, heart, lung, adrenal gland.
Species:  Rat
Technique:  RT-PCR
References:  21
Functional Assays
Cation influx in response to DAG generated by receptor-mediated activation of PLC-β and PLC-γ.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Cation influx, using calcium imaging and patch clamp.
References:  12
Physiological Functions
TRPC6 is essential for proper regulation of podocyte structure and function.
Species:  Human
Tissue:  Kidney.
References:  11,24,34
Physiological Consequences of Altering Gene Expression
The trpc6 knockout mouse has increased vascular smooth muscle contractility.
Species:  Mouse
Tissue:  Vascular smooth muscle
References:  8
Trpc6 null mice show a reduced exploration in the square open field and the elevated star maze tests.
Species:  Mouse
Tissue:  Brain
References:  1
Transgenic mouse expressing dominant-negative Trpc6 shows attenuated cardiac hypertrophic response following pressure-overload stimulation.
Species:  Mouse
Tissue:  Heart
References:  35
In mice, ablating the expression of both Trpc6 and Trpc7 eliminates intrinsic light response of the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (M1-ipRGCs).
Species:  Mouse
Tissue:  Retina, iris
References:  37
Loss of Trpc6 reduces allergic airway response and indicates that activation of Trpc6 channels is essential for lung ischemia-reperfusion induced oedema in mice.
Species:  Mouse
Tissue:  Lung
References:  27,33
Trpc6 null mice show impaired dermal and cardiac wound healing after injury.
Species:  Mouse
Tissue:  Heart
References:  6
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J
MGI:109523  MP:0005595 abnormal vascular smooth muscle physiology PMID: 16055711 
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J
MGI:109523  MP:0000250 abnormal vasoconstriction PMID: 16055711 
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J
MGI:109523  MP:0002842 increased systemic arterial blood pressure PMID: 16055711 
Trpc6tm1Lbi Trpc6tm1Lbi/Trpc6tm1Lbi
involves: 129S/SvEv * C57BL/6J
MGI:109523  MP:0003025 increased vasoconstriction PMID: 16055711 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Focal segmental glomerulosclerosis 2; FSGS2
Synonyms: Focal segmental glomerulosclerosis [Disease Ontology: DOID:1312]
Disease Ontology: DOID:1312
OMIM: 603965
Orphanet: ORPHA93213
References:  24,34
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human M132T 11
Missense Human N143S 24,34
Missense Human S270T 24,34
Missense Human R895C 24,34
Nonsense Human K874X 24,34


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1. Beis D, Schwarting RK, Dietrich A. (2011) Evidence for a supportive role of classical transient receptor potential 6 (TRPC6) in the exploration behavior of mice. Physiol. Behav., 102 (2): 245-50. [PMID:21059368]

2. Boulay G. (2002) Ca(2+)-calmodulin regulates receptor-operated Ca(2+) entry activity of TRPC6 in HEK-293 cells. Cell Calcium, 32 (4): 201-7. [PMID:12379180]

3. Boulay G, Zhu X, Peyton M, Jiang M, Hurst R, Stefani E, Birnbaumer L. (1997) Cloning and expression of a novel mammalian homolog of Drosophila transient receptor potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein. J. Biol. Chem., 272 (47): 29672-80. [PMID:9368034]

4. Boulay ME, Boulet LP. (2002) Lower airway inflammatory responses to repeated very-low-dose allergen challenge in allergic rhinitis and asthma. Clin. Exp. Allergy, 32 (10): 1441-7. [PMID:12372123]

5. Carrasquillo R, Tian D, Krishna S, Pollak MR, Greka A, Schlöndorff J. (2012) SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity. BMC Cell Biol., 13: 33. [PMID:23171048]

6. Davis J, Burr AR, Davis GF, Birnbaumer L, Molkentin JD. (2012) A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo. Dev. Cell, 23 (4): 705-15. [PMID:23022034]

7. Dietrich A, Kalwa H, Rost BR, Gudermann T. (2005) The diacylgylcerol-sensitive TRPC3/6/7 subfamily of cation channels: functional characterization and physiological relevance. Pflugers Arch., 451 (1): 72-80. [PMID:15971081]

8. Dietrich A, Mederos Y Schnitzler M, Gollasch M, Gross V, Storch U, Dubrovska G, Obst M, Yildirim E, Salanova B, Kalwa H et al.. (2005) Increased vascular smooth muscle contractility in TRPC6-/- mice. Mol. Cell. Biol., 25 (16): 6980-9. [PMID:16055711]

9. Friedlova E, Grycova L, Holakovska B, Silhan J, Janouskova H, Sulc M, Obsilova V, Obsil T, Teisinger J. (2010) The interactions of the C-terminal region of the TRPC6 channel with calmodulin. Neurochem. Int., 56 (2): 363-6. [PMID:19932145]

10. Harteneck C, Gollasch M. (2011) Pharmacological modulation of diacylglycerol-sensitive TRPC3/6/7 channels. Curr Pharm Biotechnol, 12 (1): 35-41. [PMID:20932261]

11. Heeringa SF, Möller CC, Du J, Yue L, Hinkes B, Chernin G, Vlangos CN, Hoyer PF, Reiser J, Hildebrandt F. (2009) A novel TRPC6 mutation that causes childhood FSGS. PLoS ONE, 4 (11): e7771. [PMID:19936226]

12. Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature, 397 (6716): 259-63. [PMID:9930701]

13. Häfner S, Burg F, Kannler M, Urban N, Mayer P, Dietrich A, Trauner D, Broichhagen J, Schaefer M. (2018) A (+)-Larixol Congener with High Affinity and Subtype Selectivity toward TRPC6. ChemMedChem, 13 (10): 1028-1035. [PMID:29522264]

14. Inada H, Iida T, Tominaga M. (2006) Different expression patterns of TRP genes in murine B and T lymphocytes. Biochem. Biophys. Res. Commun., 350 (3): 762-7. [PMID:17027915]

15. Inoue R, Okada T, Onoue H, Hara Y, Shimizu S, Naitoh S, Ito Y, Mori Y. (2001) The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel. Circ. Res., 88 (3): 325-32. [PMID:11179201]

16. Jang Y, Lee Y, Kim SM, Yang YD, Jung J, Oh U. (2012) Quantitative analysis of TRP channel genes in mouse organs. Arch. Pharm. Res., 35 (10): 1823-30. [PMID:23139135]

17. Leuner K, Heiser JH, Derksen S, Mladenov MI, Fehske CJ, Schubert R, Gollasch M, Schneider G, Harteneck C, Chatterjee SS et al.. (2010) Simple 2,4-diacylphloroglucinols as classic transient receptor potential-6 activators--identification of a novel pharmacophore. Mol. Pharmacol., 77 (3): 368-77. [PMID:20008516]

18. Leuner K, Kazanski V, Müller M, Essin K, Henke B, Gollasch M, Harteneck C, Müller WE. (2007) Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels. FASEB J., 21 (14): 4101-11. [PMID:17666455]

19. Maier T, Follmann M, Hessler G, Kleemann HW, Hachtel S, Fuchs B, Weissmann N, Linz W, Schmidt T, Löhn M et al.. (2015) Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels. Br. J. Pharmacol., 172 (14): 3650-60. [PMID:25847402]

20. Miehe S, Crause P, Schmidt T, Löhn M, Kleemann HW, Licher T, Dittrich W, Rütten H, Strübing C. (2012) Inhibition of diacylglycerol-sensitive TRPC channels by synthetic and natural steroids. PLoS ONE, 7 (4): e35393. [PMID:22530015]

21. Mizuno N, Kitayama S, Saishin Y, Shimada S, Morita K, Mitsuhata C, Kurihara H, Dohi T. (1999) Molecular cloning and characterization of rat trp homologues from brain. Brain Res. Mol. Brain Res., 64 (1): 41-51. [PMID:9889314]

22. Parenti A, De Logu F, Geppetti P, Benemei S. (2016) What is the evidence for the role of TRP channels in inflammatory and immune cells?. Br. J. Pharmacol., 173 (6): 953-69. [PMID:26603538]

23. Qu C, Ding M, Zhu Y, Lu Y, Du J, Miller M, Tian J, Zhu J, Xu J, Wen M et al.. (2017) Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels. J. Med. Chem., 60 (11): 4680-4692. [PMID:28395140]

24. Reiser J, Polu KR, Möller CC, Kenlan P, Altintas MM, Wei C, Faul C, Herbert S, Villegas I, Avila-Casado C et al.. (2005) TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat. Genet., 37 (7): 739-44. [PMID:15924139]

25. Riccio A, Medhurst AD, Mattei C, Kelsell RE, Calver AR, Randall AD, Benham CD, Pangalos MN. (2002) mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Brain Res. Mol. Brain Res., 109 (1-2): 95-104. [PMID:12531519]

26. Richter JM, Schaefer M, Hill K. (2014) Clemizole hydrochloride is a novel and potent inhibitor of transient receptor potential channel TRPC5. Mol. Pharmacol., 86 (5): 514-21. [PMID:25140002]

27. Sel S, Rost BR, Yildirim AO, Sel B, Kalwa H, Fehrenbach H, Renz H, Gudermann T, Dietrich A. (2008) Loss of classical transient receptor potential 6 channel reduces allergic airway response. Clin. Exp. Allergy, 38 (9): 1548-58. [PMID:18631347]

28. Seo K, Rainer PP, Shalkey Hahn V, Lee DI, Jo SH, Andersen A, Liu T, Xu X, Willette RN, Lepore JJ et al.. (2014) Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy. Proc. Natl. Acad. Sci. U.S.A., 111 (4): 1551-6. [PMID:24453217]

29. Soboloff J, Spassova M, Xu W, He LP, Cuesta N, Gill DL. (2005) Role of endogenous TRPC6 channels in Ca2+ signal generation in A7r5 smooth muscle cells. J. Biol. Chem., 280 (48): 39786-94. [PMID:16204251]

30. Takumida M, Anniko M. (2009) Expression of canonical transient receptor potential channel (TRPC) 1-7 in the mouse inner ear. Acta Otolaryngol., 129 (12): 1351-8. [PMID:19922081]

31. Urban N, Wang L, Kwiek S, Rademann J, Kuebler WM, Schaefer M. (2016) Identification and Validation of Larixyl Acetate as a Potent TRPC6 Inhibitor. Mol. Pharmacol., 89 (1): 197-213. [PMID:26500253]

32. Washburn DG, Holt DA, Dodson J, McAtee JJ, Terrell LR, Barton L, Manns S, Waszkiewicz A, Pritchard C, Gillie DJ et al.. (2013) The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore. Bioorg. Med. Chem. Lett., 23 (17): 4979-84. [PMID:23886683]

33. Weissmann N, Sydykov A, Kalwa H, Storch U, Fuchs B, Mederos y Schnitzler M, Brandes RP, Grimminger F, Meissner M, Freichel M et al.. (2012) Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice. Nat Commun, 3: 649. [PMID:22337127]

34. Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL et al.. (2005) A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science, 308 (5729): 1801-4. [PMID:15879175]

35. Wu X, Eder P, Chang B, Molkentin JD. (2010) TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc. Natl. Acad. Sci. U.S.A., 107 (15): 7000-5. [PMID:20351294]

36. Xu X, Lozinskaya I, Costell M, Lin Z, Ball JA, Bernard R, Behm DJ, Marino JP, Schnackenberg CG. (2013) Characterization of Small Molecule TRPC3 and TRPC6 agonist and Antagonists. Biophys. J, 104 (2): 454a Meeting abstract. DOI: 10.1016/j.bpj.2012.11.2513

37. Xue T, Do MT, Riccio A, Jiang Z, Hsieh J, Wang HC, Merbs SL, Welsbie DS, Yoshioka T, Weissgerber P et al.. (2011) Melanopsin signalling in mammalian iris and retina. Nature, 479 (7371): 67-73. [PMID:22051675]

38. Yuan JP, Zeng W, Dorwart MR, Choi YJ, Worley PF, Muallem S. (2009) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat. Cell Biol., 11 (3): 337-43. [PMID:19182790]

39. Zagranichnaya TK, Wu X, Villereal ML. (2005) Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. J. Biol. Chem., 280 (33): 29559-69. [PMID:15972814]


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