TRPC3

Summary

TRPC3 (transient receptor potential cation channel subfamily C member 3, HGNC:12335) is a protein-coding gene on chromosome 4q27, encoding Short transient receptor potential channel 3 (Q13507). Forms a receptor-activated non-selective calcium permeant cation channel.

The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7222 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 41 (Moderate, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 219 total — 1 pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001130698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12335
Approved symbol	TRPC3
Name	transient receptor potential cation channel subfamily C member 3
Location	4q27
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138741
Ensembl biotype	protein_coding
OMIM	602345
Entrez	7222

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000264811, ENST00000379645, ENST00000502968, ENST00000506449, ENST00000513531, ENST00000871535, ENST00000949674

RefSeq mRNA: 3 — MANE Select: NM_001130698 NM_001130698, NM_001366479, NM_003305

CCDS: CCDS3725, CCDS47130

Canonical transcript exons

ENST00000379645 — 12 exons

Exon	Start	End
ENSE00001176909	121874481	121879878
ENSE00001481966	121932271	121933042
ENSE00001481970	121951466	121952060
ENSE00003467503	121882354	121882429
ENSE00003481876	121914780	121914944
ENSE00003483379	121899612	121899695
ENSE00003553858	121904322	121904517
ENSE00003560841	121902852	121903061
ENSE00003565707	121907303	121907567
ENSE00003576721	121911877	121912093
ENSE00003609053	121910154	121910387
ENSE00003632447	121925018	121925206

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 91.51.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4287 / max 37.9103, expressed in 198 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53844	0.4287	198

Top tissues by expression

265 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.51	gold quality
secondary oocyte	CL:0000655	89.49	gold quality
oocyte	CL:0000023	86.23	gold quality
endothelial cell	CL:0000115	83.93	gold quality
pituitary gland	UBERON:0000007	76.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.58	gold quality
adenohypophysis	UBERON:0002196	74.31	gold quality
ventricular zone	UBERON:0003053	73.75	gold quality
mucosa of stomach	UBERON:0001199	73.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.90	gold quality
cortical plate	UBERON:0005343	71.14	gold quality
putamen	UBERON:0001874	71.01	gold quality
primary visual cortex	UBERON:0002436	70.70	gold quality
ganglionic eminence	UBERON:0004023	67.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.36	gold quality
prefrontal cortex	UBERON:0000451	67.17	gold quality
stromal cell of endometrium	CL:0002255	67.00	gold quality
caudate nucleus	UBERON:0001873	66.95	gold quality
occipital lobe	UBERON:0002021	66.72	gold quality
right lung	UBERON:0002167	65.27	gold quality
cerebellar vermis	UBERON:0004720	65.03	gold quality
cerebellum	UBERON:0002037	63.75	gold quality
cerebellar cortex	UBERON:0002129	63.47	gold quality
cerebellar hemisphere	UBERON:0002245	63.25	gold quality
urinary bladder	UBERON:0001255	62.40	gold quality
mucosa of urinary bladder	UBERON:0001259	62.07	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	62.06	gold quality
cingulate cortex	UBERON:0003027	62.04	gold quality
gall bladder	UBERON:0002110	61.75	gold quality
anterior cingulate cortex	UBERON:0009835	61.72	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	4.80
E-CURD-97	no	39.71
E-ANND-3	no	6.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting TRPC3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337

Literature-anchored findings (GeneRIF, showing 40)

• Comparison of human TRPC3 channels in receptor-activated and store-operated modes. (PMID:11943785)
• may be candidate protein forming store-operated calcium entry channels in term pregnant human myometrium (PMID:12356946)
• receptor-mediated activation of phospholipase C in intact cells activates TRPC3 via diacylglycerol production. (PMID:12606542)
• overexpression of transient receptor potential channel 3 in myometrium cells enhanced thapsigargin-, oxytocin-, and OAG-induced Ca2+ entry (PMID:12700192)
• the CIRB region of TRPC3 is involved in its targeting to the plasma membrane by a mechanism that does not involve interaction with IP3 receptors (PMID:12730194)
• Expression of the channel in human esophagogastric junction. (PMID:12736151)
• TRPC3 channels are important for the TCR-dependent Ca2+ entry pathway. The TRPC3 gene was found to be damaged in human T-cell mutants defective in Ca2+ influx. (PMID:12736256)
• the pattern of TRPC3 and TRPC6 glycosylation determines regulation of their activity (PMID:12970363)
• functional and physical interaction of nonselective TRPC cation channels with NCX proteins as a novel principle of TRPC-mediated Ca(2+) signaling. (PMID:14736881)
• TRPC3 channels are directly phosphorylated by PKG at position T11 and S263, and this phosphorylation abolished the store-operated Ca2+ influx mediated by TRPC3 channels in HEK293 cells. (PMID:14983059)
• diacylglycerol activation of TRPC3 requires src kinase (PMID:15271991)
• TRPC channel overexpression may be partially responsible for the increased pulmonary artert smooth muscle cell proliferation and pulmonary vascular medial hypertrophy in pulmonary hypertension patients. (PMID:15358862)
• TRPC3/TRPC6 channels are localized to the apical region of polarized epithelial cells, which in salivary gland ducts could contribute to the regulation of salivary [Ca2+] and secretion [TRPC6] (PMID:15623527)
• a strong functional link between the operation of expressed TRPC channels and endogenous SOC activity. (PMID:15647288)
• the partial PH domain of PLC-gamma1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3 (PMID:15744307)
• TRPC1 and TRPC3 co-assemble, via N-terminal interactions, to form a heteromeric store-operated non-selective cation channel in HSY cells (PMID:15834157)
• endogenous TRPC1, TRPC3, and TRPC7 participate in forming heteromeric store-operated channels, whereas TRPC3 and TRPC7 can also participate in forming heteromeric receptor-operated channels. (PMID:15972814)
• Protein kinase C can inactivate TRPC3 indirectly by activating protein kinase G, and directly by phosphorylation on Ser-712. (PMID:16331690)
• Cholesterol loading as well as PLC stimulation increased surface expression of TRPC3. Promotion of TRPC3 membrane expression by cholesterol was persistent, while PLC-mediated enhancement of plasma membrane expression of TRPC3 was transient. (PMID:16448384)
• expression of TRPC3 is tightly regulated during muscle cell differentiation and functional interaction between TRPC3 and RyR1 may regulate the gain of SR Ca(2+) release independent of SR Ca(2+) load (PMID:16484216)
• therefore suggesting that TRPC1 and/or TRPC3 proteins are responsible for the response to alpha-adrenergic stimulation but that TRPC1, TPRC3 and TRPV6 proteins, expressed alone or concomitantly, are not sufficient for SOC formation. (PMID:16529812)
• propose that TRPC3 and TRPC4 are subunits of native endothelial cation channels that are governed by the cellular redox state (PMID:16537542)
• observations suggest a model in which TFII-I suppresses agonist-induced calcium entry by competing with TRPC3 for binding to phospholipase C-gamma (PMID:17023658)
• we summarize current knowledge on properties and possible signalling functions of TRPC3 and discuss the potential biological relevance of this signalling molecule–{REVIEW} (PMID:17217051)
• This structure implies that the TRP superfamily has diversely evolved as sensors specialized for various signals, rather than as simple ion-conducting apparatuses. (PMID:17258231)
• Orai1 physically interacts with the N and C termini of TRPC3 and TRPC6 (PMID:17360584)
• TRPC3 is required for the formation of functional store-operated channels in A431 cells (PMID:17569672)
• the TRPC3 tetramer dissociates to monomers under high-salt conditions (PMID:17967814)
• Significant correlation is observed between TRPC3 transcripts, systolic blood pressure, and expression of proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. (PMID:18177730)
• TRPC3 and RyR1 are functionally engaged via linker proteins in skeletal muscle (PMID:18215135)
• This study is believed to provide the first clear evidence that TRPM4b interacts physically with TRPC3. (PMID:18262493)
• TRPC3 Tyr(226) is critical in Epo-dependent activation of TRPC3 (PMID:18276585)
• Results show that overexpression of the putative store-operated calcium channel TRPC3 reduces the calcium content of intracellular stores, but does not enhance agonist-evoked or store-dependent calcium entry. (PMID:18431718)
• data show that calcium influx in HL-60 cells relies on TRPC channels 1,3, and 6, and Orai1 for allowing NADPH oxidase activation (PMID:18436303)
• Endogenous TRPC3 regulates astrocytic calcium divalent cation (Ca2+) dynamics, which in turn modulates the pathways leading to morphological change in astrocytes. (PMID:18478545)
• These results identify TRPC3 as a key Ca2+ entry channel in a subset of CD133+ stem cells. (PMID:18602918)
• plays a role in pathogenesis and progression of heart failure by activating NFAT transcription factor. Thus, inhibitors target this molecule will be developed as cardiotonic agents for heart failure.(review) (PMID:18700317)
• TRPC3 controls agonist-stimulated intracellular Ca(2+) release by mediating interaction between IP(3)R and RACK1 (PMID:18755685)
• Report the involvement of native TRPC3 proteins in ATP-dependent expression of VCAM-1 and monocyte adherence in coronary artery endothelial cells. (PMID:18787184)
• results showed, for the first time, that histamine could activate TRPC3 via histamine H(2) receptors, and both PLC and PLD participated in this process (PMID:19032951)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpc3	ENSDARG00000098291
mus_musculus	Trpc3	ENSMUSG00000027716
rattus_norvegicus	Trpc3	ENSRNOG00000016070
caenorhabditis_elegans		WBGENE00006614

Paralogs (5): TRPC7 (ENSG00000069018), TRPC5 (ENSG00000072315), TRPC4 (ENSG00000133107), TRPC6 (ENSG00000137672), TRPC1 (ENSG00000144935)

Protein

Protein identifiers

Short transient receptor potential channel 3 — Q13507 (reviewed: Q13507)

Alternative names: Transient receptor protein 3

All UniProt accessions (4): Q13507, D6R902, D6RC49, J3QTB0

UniProt curated annotations — full annotation on UniProt →

Function. Forms a receptor-activated non-selective calcium permeant cation channel. Forms a receptor-activated non-selective calcium permeant cation channel. May be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors.

Subunit / interactions. Homotetramer. Interacts with ITPR1. Interacts with ITPR3. Interacts with MX1. Interacts with RNF24. Interacts with JPH2; the interaction is involved in maintaining Ca(2+) homeostasis in skeletal muscle and is mediated by JPH2 ‘Ser-165’ phosphorylation. Interacts with isoform short of TRPC1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed predominantly in brain and at much lower levels in ovary, colon, small intestine, lung, prostate, placenta and testis.

Disease relevance. Spinocerebellar ataxia 41 (SCA41) [MIM:616410] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C. Activated by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May be activated by internal calcium store depletion. Inhibited by intracellular Ca(2+).

Domain organisation. The cytoplasmic portion of the protein is required for channel assembly and gating.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC3 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13507-2	1	yes
Q13507-3	2

RefSeq proteins (3): NP_001124170, NP_001353408, NP_003296 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR002153	TRPC_channel	Family
IPR005459	TRPC3_channel	Family
IPR005821	Ion_trans_dom	Domain
IPR013555	TRP_dom	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00520, PF08344, PF12796

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (103 total): helix 43, strand 14, binding site 8, topological domain 7, turn 7, transmembrane region 6, repeat 5, mutagenesis site 4, region of interest 2, sequence conflict 2, chain 1, compositionally biased region 1, glycosylation site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
9U5C	ELECTRON MICROSCOPY	2.25
9OLM	ELECTRON MICROSCOPY	2.5
9KDB	ELECTRON MICROSCOPY	2.67
7DXB	ELECTRON MICROSCOPY	2.7
9KDD	ELECTRON MICROSCOPY	2.7
9VFI	ELECTRON MICROSCOPY	2.72
9OLK	ELECTRON MICROSCOPY	2.8
9KDC	ELECTRON MICROSCOPY	3.01
7DXC	ELECTRON MICROSCOPY	3.06
9OLL	ELECTRON MICROSCOPY	3.1
7DXE	ELECTRON MICROSCOPY	3.2
6CUD	ELECTRON MICROSCOPY	3.3
9OLX	ELECTRON MICROSCOPY	3.3
9OPU	ELECTRON MICROSCOPY	3.3
9KDE	ELECTRON MICROSCOPY	3.34
7DXD	ELECTRON MICROSCOPY	3.9
6D7L	ELECTRON MICROSCOPY	4
5ZBG	ELECTRON MICROSCOPY	4.36
6DJS	ELECTRON MICROSCOPY	5.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13507-F1	78.42	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 158; 525; 528; 543; 871; 874; 876; 883

Glycosylation sites (1): 489

Mutagenesis-validated functional residues (4):

Position	Phenotype
525	no effect on inhibition by ca(2+) or thermostability. no effect on activation by diacylglycerol (dag) analog; when assoc
874	retains robust ca(2+) inhibition with moderate enhancement of thermostability in low-ca(2+) conditions. no effect on act
883	loss of inhibition by intracellular ca(2+) and loss of ca(2+)-induced thermostability. impaired extracellular ca(2+) inh
888	loss of inhibition by intracellular ca(2+) and loss of ca(2+)-induced thermostability.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis
R-HSA-139853	Elevation of cytosolic Ca2+ levels
R-HSA-3295583	TRP channels
R-HSA-418890	Role of second messengers in netrin-1 signaling
R-HSA-9022699	MECP2 regulates neuronal receptors and channels

MSigDB gene sets: 202 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_SINGLE_FERTILIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PHOTOTRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MUSCLE_HYPERTROPHY, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION

GO Biological Process (12): calcium ion transport (GO:0006816), single fertilization (GO:0007338), phototransduction (GO:0007602), positive regulation of calcium ion transport into cytosol (GO:0010524), response to ATP (GO:0033198), regulation of cytosolic calcium ion concentration (GO:0051480), response to calcium ion (GO:0051592), calcium ion transmembrane transport (GO:0070588), positive regulation of cardiac muscle hypertrophy in response to stress (GO:1903244), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (7): calcium-activated cation channel activity (GO:0005227), calcium channel activity (GO:0005262), store-operated calcium channel activity (GO:0015279), metal ion binding (GO:0046872), inositol 1,4,5 trisphosphate binding (GO:0070679), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), cation channel complex (GO:0034703), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Platelet calcium homeostasis	1
Stimuli-sensing channels	1
Netrin-1 signaling	1
Transcriptional Regulation by MECP2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
metal ion transport	1
fertilization	1
signal transduction	1
detection of light stimulus	1
positive regulation of cytosolic calcium ion concentration	1
regulation of calcium ion transport into cytosol	1
calcium ion transport into cytosol	1
positive regulation of calcium ion transmembrane transport	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
intracellular calcium ion homeostasis	1
response to metal ion	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
positive regulation of cardiac muscle hypertrophy	1
positive regulation of cardiac muscle adaptation	1
cardiac muscle hypertrophy in response to stress	1
regulation of cardiac muscle hypertrophy in response to stress	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic ion-gated channel activity	1
ligand-gated monoatomic cation channel activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
calcium channel activity	1
cation binding	1
anion binding	1
alcohol binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPC3	TRPC4	Q9UBN4	973
TRPC3	STIM1	Q13586	956
TRPC3	TRPM4	Q8TD43	942
TRPC3	ORAI3	Q9BRQ5	931
TRPC3	ITPR1	Q14643	926
TRPC3	ORAI1	Q96D31	921
TRPC3	ITPR2	Q14571	907
TRPC3	TRPC1	P48995	898
TRPC3	TRPC5	Q9UL62	882
TRPC3	STIM2	Q9P246	877
TRPC3	ORAI2	Q96SN7	872
TRPC3	TRPC6	Q9Y210	866
TRPC3	PLCG1	P19174	854
TRPC3	CALML5	Q9NZT1	846
TRPC3	CALML6	Q8TD86	845
TRPC3	CALML3	P27482	845

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ITPR3	TRPC3	psi-mi:“MI:0915”(physical association)	0.590
TRPC3	ITPR3	psi-mi:“MI:0915”(physical association)	0.590
TRPC3	ORAI1	psi-mi:“MI:0407”(direct interaction)	0.540
TRPC3	ORAI1	psi-mi:“MI:0915”(physical association)	0.540
TRPC3	MX1	psi-mi:“MI:0915”(physical association)	0.520
Plcg1	TRPC3	psi-mi:“MI:0915”(physical association)	0.510
TRPC3	Plcg1	psi-mi:“MI:0915”(physical association)	0.510
TRPC3	ORAI3	psi-mi:“MI:0915”(physical association)	0.400
TRPC3	ORAI2	psi-mi:“MI:0915”(physical association)	0.400
TRPC3	SEC24A	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): TRPC3 (Affinity Capture-Western), TRPC3 (Affinity Capture-Western), TRPC3 (Affinity Capture-Western), TRPC3 (Affinity Capture-Western), TRPC3 (Affinity Capture-MS), FKBP1A (Affinity Capture-Western), TRPC3 (Affinity Capture-Western), TRPC3 (Affinity Capture-Western), TRPC6 (Affinity Capture-Western), TRPC6 (FRET), TRPC7 (FRET), TRPC3 (FRET), TRPC3 (Reconstituted Complex), TRPC3 (Co-fractionation), TRPC3 (Affinity Capture-RNA)

ESM2 similar proteins: A1A5B4, A2A259, A2AIR5, E9PTA2, F6RG56, H2Q5A1, O35245, O62826, O70212, O94759, P02715, P04758, P09690, P11230, P13536, P23979, P25109, P35563, P37088, Q04671, Q13507, Q13563, Q4GZT3, Q60HE8, Q6IVV8, Q7Z403, Q86V40, Q8BWC0, Q8MIQ9, Q8R4F0, Q8TCT7, Q8TCU5, Q8TDD5, Q91YD4, Q96BD0, Q99J21, Q9EQJ0, Q9GZU1, Q9HA82, Q9JJH7

Diamond homologs: O18784, O35119, O62826, O62852, P19334, P34586, P48994, P48995, P79100, Q13507, Q61056, Q61143, Q9HCX4, Q9JMI9, Q9MYV9, Q9MYW0, Q9QUQ5, Q9QX01, Q9QX29, Q9QZC1, Q9R244, Q9R283, Q9TUN9, Q9UBN4, Q9UL62, Q9VJJ7, Q9WVC5, Q9Y210, A2A259, H2LRU7, O35245, Q13563, Q4GZT3, Q6IVV8, Q7TN88, Q9JLG4, Q9NZM6, Q9P0L9, Q9U1S7, O54935

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PRKG1	down-regulates	TRPC3	phosphorylation
PRKCA	down-regulates	TRPC3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

219 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	128
Likely benign	70
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1027487	NM_001130698.2(TRPC3):c.1419del (p.Val474fs)	Pathogenic

SpliceAI

2555 predictions. Top by Δscore:

Variant	Effect	Δscore
4:121882427:CTG:C	acceptor_gain	1.0000
4:121882428:TG:T	acceptor_gain	1.0000
4:121882430:C:CC	acceptor_gain	1.0000
4:121904516:CA:C	acceptor_gain	1.0000
4:121904518:C:CC	acceptor_gain	1.0000
4:121907414:T:TA	donor_gain	1.0000
4:121908015:A:C	acceptor_gain	1.0000
4:121910149:CTTA:C	donor_loss	1.0000
4:121910150:TTACC:T	donor_loss	1.0000
4:121910151:TA:T	donor_loss	1.0000
4:121910152:ACCA:A	donor_loss	1.0000
4:121910153:C:A	donor_loss	1.0000
4:121911871:ACTT:A	donor_loss	1.0000
4:121911872:CTT:C	donor_loss	1.0000
4:121911874:T:TG	donor_loss	1.0000
4:121911875:A:AC	donor_gain	1.0000
4:121911876:C:CC	donor_gain	1.0000
4:121912089:CCCAG:C	acceptor_gain	1.0000
4:121912090:CCAG:C	acceptor_gain	1.0000
4:121912090:CCAGC:C	acceptor_gain	1.0000
4:121912091:CAG:C	acceptor_gain	1.0000
4:121912091:CAGC:C	acceptor_gain	1.0000
4:121912092:AGCTG:A	acceptor_loss	1.0000
4:121912093:GC:G	acceptor_loss	1.0000
4:121912094:C:CC	acceptor_gain	1.0000
4:121914778:AC:A	donor_gain	1.0000
4:121914779:CC:C	donor_gain	1.0000
4:121914779:CCCTG:C	donor_gain	1.0000
4:121914941:CAAA:C	acceptor_gain	1.0000
4:121914945:C:CC	acceptor_gain	1.0000

AlphaMissense

6101 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000034923 (4:121921724 A>G), RS1000049448 (4:121874468 G>A,C), RS1000084641 (4:121888057 T>A), RS1000108917 (4:121911051 T>C), RS1000117544 (4:121923710 C>T), RS1000165324 (4:121942919 C>T), RS1000210228 (4:121950384 C>T), RS1000232034 (4:121908965 G>A), RS1000284514 (4:121916359 C>A,T), RS1000292451 (4:121910770 C>G), RS1000360608 (4:121936293 A>G), RS1000448106 (4:121874773 A>G), RS1000470364 (4:121943476 A>T), RS1000588013 (4:121880484 G>A), RS1000598980 (4:121926889 T>C)

Disease associations

OMIM: gene MIM:602345 | disease phenotypes: MIM:616410, MIM:190300

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 41	Moderate	Autosomal dominant

Mondo (2): spinocerebellar ataxia type 41 (MONDO:0014626), essential tremor (MONDO:0003233)

Orphanet (2): Spinocerebellar ataxia type 41 (Orphanet:458798), NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001251	Ataxia
HP:0001272	Cerebellar atrophy
HP:0002066	Gait ataxia
HP:0002172	Postural instability
HP:0002317	Unsteady gait
HP:0003581	Adult onset
HP:0003676	Progressive
HP:0006855	Cerebellar vermis atrophy

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002945_20	Emphysema imaging phenotypes	9.000000e-07
GCST002945_9	Emphysema imaging phenotypes	1.000000e-06
GCST005790_94	Rosacea symptom severity	4.000000e-06
GCST008644_4	Celiac disease and Rheumatoid arthritis	6.000000e-09
GCST009798_73	Asthma	5.000000e-14
GCST90002392_667	Mean corpuscular volume	2.000000e-58
GCST90002396_232	Mean reticulocyte volume	6.000000e-57
GCST90002397_21	Mean spheric corpuscular volume	2.000000e-58
GCST90014325_45	Asthma	3.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement
EFO:0009180	rosacea severity measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2417348 (SINGLE PROTEIN), CHEMBL4296083 (PROTEIN COMPLEX), CHEMBL4523662 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,752 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1407943	CLEMIZOLE	2	3,752

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Transient Receptor Potential channels (TRP)

Most potent curated ligand interactions (14 total), top 14:

Ligand	Action	Affinity	Parameter
pyrazolopyrimidine 4n	Activation	7.72	pEC50
GSK2833503A	Channel blocker	7.68	pIC50
GSK1702934A	Agonist	7.1	pEC50
GSK417651A	Antagonist	7.1	pIC50
Gd3+	Antagonist	7.0	pEC50
SAR7334	Channel blocker	6.55	pIC50
BTP2	Antagonist	6.5	pIC50
Pyr3	Channel blocker	6.15	pIC50
Pyr10	Antagonist	6.14	pIC50
SH045	Channel blocker	6.08	pIC50
norgestimate	Channel blocker	5.52	pKi
La3+	Antagonist	5.4	pIC50
clemizole	Channel blocker	5.04	pIC50
2-APB	Antagonist	5.0	pIC50

ChEMBL bioactivities

80 potent at pChembl≥5 of 86 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL2418811
8.43	IC50	3.68	nM	CHEMBL5884133
8.39	IC50	4.03	nM	CHEMBL5870151
8.37	IC50	4.28	nM	CHEMBL5995011
8.30	IC50	5	nM	CHEMBL2418809
8.27	IC50	5.39	nM	CHEMBL6047787
8.21	IC50	6.22	nM	CHEMBL5759191
8.18	IC50	6.64	nM	CHEMBL5835028
8.14	IC50	7.2	nM	CHEMBL5741863
8.12	IC50	7.55	nM	CHEMBL5901204
8.10	IC50	7.97	nM	CHEMBL5832744
8.08	IC50	8.31	nM	CHEMBL5774406
8.00	IC50	10	nM	CHEMBL5558723
7.95	IC50	11.3	nM	CHEMBL6040572
7.84	IC50	14.3	nM	CHEMBL5989633
7.80	IC50	16	nM	CHEMBL5971115
7.76	IC50	17.5	nM	CHEMBL5776256
7.75	IC50	17.7	nM	CHEMBL5847664
7.72	EC50	19	nM	CHEMBL4085233
7.65	IC50	22.5	nM	CHEMBL5835965
7.62	IC50	24	nM	CHEMBL5864721
7.59	IC50	25.5	nM	CHEMBL5892236
7.59	IC50	25.5	nM	CHEMBL6065445
7.50	IC50	32	nM	CHEMBL2418809
7.49	IC50	32.2	nM	CHEMBL5952105
7.41	IC50	38.8	nM	CHEMBL5794171
7.41	IC50	39.2	nM	CHEMBL5839618
7.37	IC50	42.5	nM	CHEMBL5974801
7.34	IC50	46.1	nM	CHEMBL5887941
7.33	IC50	46.4	nM	CHEMBL5883956
7.29	IC50	50.7	nM	CHEMBL6046547
7.23	IC50	58.8	nM	CHEMBL5754111
7.19	IC50	64.5	nM	CHEMBL5993383
7.16	IC50	69.5	nM	CHEMBL5832093
7.14	IC50	72.3	nM	CHEMBL5895935
7.10	IC50	80	nM	CHEMBL2418807
7.05	IC50	90	nM	CHEMBL6102610
7.00	IC50	100	nM	CHEMBL2418811
6.93	IC50	118	nM	CHEMBL5911052
6.86	EC50	138	nM	CHEMBL4060387
6.80	IC50	160	nM	CHEMBL2418808
6.68	IC50	209	nM	CHEMBL5792157
6.63	EC50	236	nM	CHEMBL4060400
6.60	IC50	250	nM	CHEMBL2418810
6.60	IC50	250	nM	CHEMBL2418806
6.55	IC50	282	nM	CHEMBL4129809
6.52	IC50	300	nM	CHEMBL101896
6.50	IC50	316	nM	CHEMBL2418815
6.50	IC50	316	nM	CHEMBL2418814
6.43	IC50	370	nM	CHEMBL4761535

PubChem BioAssay actives

46 with measured affinity, of 155 total; 38 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[2-(4-chloro-2-fluoroanilino)-5-methyl-1,3-thiazol-4-yl]-[(2S,3S)-2,3-dimethylpiperidin-1-yl]methanone	2079998: Antagonist activity at TRPC3 (unknown origin) assessed as inhibition of channel activity	ic50	0.0030	uM
[5-chloro-2-[(6-fluoro-1,3-benzodioxol-5-yl)amino]-1,3-thiazol-4-yl]-(2,3-dimethylpiperidin-1-yl)methanone	2079998: Antagonist activity at TRPC3 (unknown origin) assessed as inhibition of channel activity	ic50	0.0050	uM
[2-(1,3-benzodioxol-5-ylamino)-1,3-thiazol-4-yl]-(3,5-dimethylpiperidin-1-yl)methanone	2079998: Antagonist activity at TRPC3 (unknown origin) assessed as inhibition of channel activity	ic50	0.0100	uM
ethyl 4-[2-methyl-7-oxo-3-[4-(trifluoromethyl)phenyl]-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447372: Agonist activity at human TRPC3 expressed in HEK293 cells assessed as induction of membrane depolarization measured for 2.5 mins in presence of 0.5 mM Ca2+ by FLIPR membrane potential dye-based fluorescence assay	ec50	0.0190	uM
[2-(1,3-benzodioxol-5-ylamino)-1,3-thiazol-4-yl]-(2,3-dimethylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.0800	uM
benzyl 4-[3-(4-chlorophenyl)-2-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447372: Agonist activity at human TRPC3 expressed in HEK293 cells assessed as induction of membrane depolarization measured for 2.5 mins in presence of 0.5 mM Ca2+ by FLIPR membrane potential dye-based fluorescence assay	ec50	0.1380	uM
(2,3-dimethylpiperidin-1-yl)-[2-[(6-fluoro-1,3-benzodioxol-5-yl)amino]-5-methyl-1,3-thiazol-4-yl]methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.1600	uM
benzyl 4-[3-(4-fluorophenyl)-2-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447372: Agonist activity at human TRPC3 expressed in HEK293 cells assessed as induction of membrane depolarization measured for 2.5 mins in presence of 0.5 mM Ca2+ by FLIPR membrane potential dye-based fluorescence assay	ec50	0.2360	uM
(2,3-dimethylpiperidin-1-yl)-[2-(4-methylanilino)-1,3-thiazol-4-yl]methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.2500	uM
[2-(4-chloro-2-fluoroanilino)-5-methyl-1,3-thiazol-4-yl]-(2,3-dimethylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.2500	uM
4-[[(1R,2R)-2-[(3R)-3-aminopiperidin-1-yl]-2,3-dihydro-1H-inden-1-yl]oxy]-3-chlorobenzonitrile	1578751: Inhibition of human TRPC3 expressed in CHO cells assessed as reduction in OAG-induced calcium influx after 10 mins by fluo-4/AM dye based FLIPR assay	ic50	0.2820	uM
N-[4-[3,5-bis(trifluoromethyl)pyrazol-1-yl]phenyl]-3-fluoropyridine-4-carboxamide	1363555: Modulation of TRPC1/TRPC3/STIM1/Orai1 in HEK cells assessed as induction of store-operated calcium entry by measuring residual activity preincubated for 30 mins followed by tBhQ-mediated Ca2+ depletion and Ca2+ re-addition to extracellular solution measured for 600 secs by Fluo-4 AM-based fluorometric assay relative to control	ic50	0.3000	uM
[2-(1,3-benzodioxol-5-ylamino)-1,3-thiazol-4-yl]-(1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.3160	uM
[2-(1,3-benzodioxol-5-ylamino)-5-methyl-1,3-thiazol-4-yl]-(1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.3160	uM
1-[4-(3,4-dichloro-2-oxo-1-pyridinyl)phenyl]-N-ethyl-5-(trifluoromethyl)pyrazole-4-carboxamide	1709630: Inhibition of human TRPC3 expressed in HEK293 cells assessed as inhibition of GSK170-induced current in absence of extracellular calcium by whole cell patch-clamp method	ic50	0.3700	uM
[2-(1,3-benzodioxol-5-ylamino)-1,3-thiazol-4-yl]-(4-methylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.4000	uM
ethyl 4-[3-(4-fluorophenyl)-2-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447372: Agonist activity at human TRPC3 expressed in HEK293 cells assessed as induction of membrane depolarization measured for 2.5 mins in presence of 0.5 mM Ca2+ by FLIPR membrane potential dye-based fluorescence assay	ec50	0.4500	uM
ethyl 1-[4-(2,3,3-trichloroprop-2-enoylamino)phenyl]-5-(trifluoromethyl)pyrazole-4-carboxylate	1709631: Inhibition of human TRPC3 expressed in HEK293 cells assessed as inhibition of GSK170-induced current in presence of 2 mM extracellular calcium by whole cell patch-clamp method	ic50	0.4700	uM
[2-(1,3-benzodioxol-5-ylamino)-1,3-thiazol-4-yl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.5000	uM
3-[1-[4-[4-ethoxycarbonyl-5-(trifluoromethyl)pyrazol-1-yl]phenyl]triazol-4-yl]benzoic acid	1363555: Modulation of TRPC1/TRPC3/STIM1/Orai1 in HEK cells assessed as induction of store-operated calcium entry by measuring residual activity preincubated for 30 mins followed by tBhQ-mediated Ca2+ depletion and Ca2+ re-addition to extracellular solution measured for 600 secs by Fluo-4 AM-based fluorometric assay relative to control	ic50	0.6000	uM
[2-(4-methylanilino)-1,3-thiazol-4-yl]-(4-methylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.6300	uM
N-[4-[3,5-bis(trifluoromethyl)pyrazol-1-yl]phenyl]-4-methylbenzenesulfonamide	1578743: Inhibition of YFP-tagged TRPC3 (unknown origin) expressed in HEK293 cells assessed as reduction carbhocol-induced receptor operated Calcium influx after 5 mins by fura-2-AM dye based assay	ic50	0.7200	uM
[2-(4-methoxyanilino)-1,3-thiazol-4-yl]-(4-methylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.8000	uM
[2-(4-chloroanilino)-1,3-thiazol-4-yl]-(4-methylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.8000	uM
[2-(4-methylanilino)-1,3-thiazol-4-yl]-(2-methylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	0.8000	uM
[(1S,4S,4aR,8aS)-4-[(3S)-3-hydroxy-3-methylpent-4-enyl]-4a,8,8-trimethyl-3-methylidene-2,4,5,6,7,8a-hexahydro-1H-naphthalen-1-yl] N-methylcarbamate	2079998: Antagonist activity at TRPC3 (unknown origin) assessed as inhibition of channel activity	ic50	0.8400	uM
[2-(4-chloro-2-fluoroanilino)-5-methyl-1,3-thiazol-4-yl]-[(2R,3R)-2,3-dimethylpiperidin-1-yl]methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	1.0000	uM
3,4-dihydro-1H-isoquinolin-2-yl-[2-(4-methoxyanilino)-1,3-thiazol-4-yl]methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	1.2600	uM
[2-(4-chloro-2-fluoroanilino)-1,3-thiazol-4-yl]-(4-methylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	1.6000	uM
2-[2-aminoethyl(naphthalen-2-ylmethyl)amino]-N-(4-hydroxyphenyl)-1,3-thiazole-4-carboxamide	2079971: Antagonist activity at human TRPC3 stably expressed in HEK293 cells inhibition of calcium influx by calcium fluorescence assay	ic50	2.4000	uM
[2-(4-methoxyanilino)-1,3-thiazol-4-yl]-(4-phenylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	2.5000	uM
3-[1-[4-[4-propan-2-yloxycarbonyl-5-(trifluoromethyl)pyrazol-1-yl]phenyl]triazol-4-yl]benzoic acid	1363555: Modulation of TRPC1/TRPC3/STIM1/Orai1 in HEK cells assessed as induction of store-operated calcium entry by measuring residual activity preincubated for 30 mins followed by tBhQ-mediated Ca2+ depletion and Ca2+ re-addition to extracellular solution measured for 600 secs by Fluo-4 AM-based fluorometric assay relative to control	ic50	3.1000	uM
N-[4-[3,5-bis(trifluoromethyl)pyrazol-1-yl]phenyl]-4-methylthiadiazole-5-carboxamide	1578743: Inhibition of YFP-tagged TRPC3 (unknown origin) expressed in HEK293 cells assessed as reduction carbhocol-induced receptor operated Calcium influx after 5 mins by fura-2-AM dye based assay	ic50	4.2100	uM
3-[1-[4-[4-pentan-2-yloxycarbonyl-5-(trifluoromethyl)pyrazol-1-yl]phenyl]triazol-4-yl]benzoic acid	1363555: Modulation of TRPC1/TRPC3/STIM1/Orai1 in HEK cells assessed as induction of store-operated calcium entry by measuring residual activity preincubated for 30 mins followed by tBhQ-mediated Ca2+ depletion and Ca2+ re-addition to extracellular solution measured for 600 secs by Fluo-4 AM-based fluorometric assay relative to control	ic50	4.4000	uM
[2-(2-chloroanilino)-1,3-thiazol-4-yl]-(4-methylpiperidin-1-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	6.3000	uM
(4-cyclohexylpiperidin-1-yl)-[2-(4-methylanilino)-1,3-thiazol-4-yl]methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	6.3000	uM
1-[(4-chlorophenyl)methyl]-2-(pyrrolidin-1-ylmethyl)benzimidazole	1578724: Inhibition of YFP-tagged human TRPC3 expressed in thapsigargin treated HEK293 cells assessed as reduction in amix-induced calcium level by fluo-4 dye based fluorescence assay	ic50	9.1000	uM
[2-(1,3-benzodioxol-5-ylamino)-5-methyl-1,3-thiazol-4-yl]-(5-methyl-7,8-dihydro-5H-1,6-naphthyridin-6-yl)methanone	765924: Inhibition of human recombinant TRPC3 expressed in HEK293-MSRII cells assessed as carbachol-stimulated Ca2+/Na+ influx after 10 mins by FLIPR assay	ic50	10.0000	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
1-oleoyl-2-acetylglycerol	affects reaction, affects transport, increases reaction, increases transport, increases activity	4
Calcium	affects reaction, affects transport, increases reaction, increases transport	3
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Valproic Acid	affects expression, decreases methylation	2
Aflatoxin B1	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ethyl-1-(4-(233-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate	affects binding, decreases activity	1
Vorinostat	increases expression	1
Asbestos	affects methylation	1
Barium	increases reaction, increases transport	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Gadolinium	affects localization, decreases activity	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Vanadates	decreases expression	1
Zeranol	increases expression	1
Methacholine Chloride	increases activity	1
Paclitaxel	increases expression	1
Thapsigargin	increases reaction, increases transport	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases expression	1

ChEMBL screening assays

45 unique, capped per target: 45 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2422304	Binding	Inhibition of human recombinant TRPC3 expressed in HEK293 cells assessed as 1-oleoyl-2-acetyl-glycerol-stimulated current at 0.01 to 0.03 uM by whole cell electrophysiology assay	The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore. — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 4 transformed cell line, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_5I80	ValiScreen human TRPC3	Transformed cell line	Female
CVCL_D1R4	Abcam K-562 TRPC3 KO	Cancer cell line	Female
CVCL_D2MR	Abcam Raji TRPC3 KO	Cancer cell line	Male
CVCL_E9Y3	HEK293-TRPC3-RFP	Transformed cell line	Female
CVCL_F0KI	HEKTrp3-9	Transformed cell line	Female
CVCL_F0KJ	HEKTrp3-65	Transformed cell line	Female
CVCL_WQ74	Abcam Jurkat TRPC3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

235 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
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