TRPC1

Summary

TRPC1 (transient receptor potential cation channel subfamily C member 1, HGNC:12333) is a protein-coding gene on chromosome 3q23, encoding Short transient receptor potential channel 1 (P48995). 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 7220 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 75 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001251845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12333
Approved symbol	TRPC1
Name	transient receptor potential cation channel subfamily C member 1
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	HTRP-1
Ensembl gene	ENSG00000144935
Ensembl biotype	protein_coding
OMIM	602343
Entrez	7220

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000273482, ENST00000460401, ENST00000476941, ENST00000480101, ENST00000698238

RefSeq mRNA: 13 — MANE Select: NM_001251845 NM_001251845, NM_001413361, NM_001413362, NM_001413363, NM_001413375, NM_001413376, NM_001413377, NM_001413378, NM_001413379, NM_001413380, NM_001413381, NM_001413382, NM_003304

CCDS: CCDS3126, CCDS58856

Canonical transcript exons

ENST00000476941 — 13 exons

Exon	Start	End
ENSE00001077571	142792824	142792967
ENSE00001077572	142743485	142743586
ENSE00001832306	142724034	142724731
ENSE00001912164	142806008	142807888
ENSE00002249274	142802169	142802344
ENSE00002332304	142780834	142781029
ENSE00002347239	142736379	142736533
ENSE00002391947	142804436	142804630
ENSE00002396396	142784704	142785040
ENSE00002419295	142791019	142791158
ENSE00002420974	142777632	142777763
ENSE00002687502	142803977	142804178
ENSE00003632334	142748258	142748460

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 93.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9874 / max 120.4199, expressed in 1571 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38958	10.1636	1562
38960	2.3002	893
38959	0.5237	304

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	93.26	gold quality
blood vessel layer	UBERON:0004797	92.22	gold quality
buccal mucosa cell	CL:0002336	91.88	gold quality
calcaneal tendon	UBERON:0003701	91.72	gold quality
tibia	UBERON:0000979	91.03	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.96	gold quality
choroid plexus epithelium	UBERON:0003911	89.57	gold quality
endothelial cell	CL:0000115	89.34	gold quality
middle temporal gyrus	UBERON:0002771	88.66	gold quality
parietal pleura	UBERON:0002400	88.05	gold quality
corpus callosum	UBERON:0002336	86.76	gold quality
ovary	UBERON:0000992	86.64	gold quality
primary visual cortex	UBERON:0002436	86.50	gold quality
left ovary	UBERON:0002119	86.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.26	gold quality
pleura	UBERON:0000977	85.87	gold quality
right ovary	UBERON:0002118	85.55	gold quality
occipital lobe	UBERON:0002021	85.53	gold quality
cerebellar vermis	UBERON:0004720	85.28	gold quality
body of uterus	UBERON:0009853	84.94	gold quality
adrenal tissue	UBERON:0018303	84.91	gold quality
tendon	UBERON:0000043	84.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	84.79	gold quality
saphenous vein	UBERON:0007318	84.68	gold quality
myometrium	UBERON:0001296	84.57	gold quality
cauda epididymis	UBERON:0004360	84.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.51	gold quality
periodontal ligament	UBERON:0008266	84.48	silver quality
mucosa of stomach	UBERON:0001199	84.18	gold quality
trigeminal ganglion	UBERON:0001675	83.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	18.30
E-ANND-3	yes	5.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, NFKB1, NFKB, RELA

miRNA regulators (miRDB)

136 targeting TRPC1, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Literature-anchored findings (GeneRIF, showing 40)

• Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1. (PMID:11983166)
• an examination of subunits in living cells (PMID:12032305)
• Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation. (PMID:12060571)
• involved in the activation of store-mediated Ca(2+) entry by coupling to IP3R1 in normal human platelets (PMID:12196544)
• may be candidate protein forming store-operated calcium entry channels in term pregnant human myometrium (PMID:12356946)
• Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. (PMID:12732636)
• Expression of the channel in human esophagogastric junction. (PMID:12736151)
• TRPC1 interaction with IP3R is signaled by Rho activation at the plasma membrane of endothelial cells, and Ca2+ entry is triggered following store depletion (PMID:12766172)
• TRPC1 store dependence is suppressed by I-mfa1 (PMID:14530267)
• TRPC1 is associated with cholesterol-rich lipid raft domains in human platelets; these domains are important for participation of TRPC1 in store-mediated Ca2+ entry in platelets. (PMID:14706284)
• analysis of hydrophobic regions of transient receptor potential Ca2+ channel TRPC1 (PMID:14707123)
• Phosphorylation of TRPC1 and Ca2+ entry were essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. (PMID:15016832)
• Ca(2+) increase related to the incorporation of 7-ketocholesterol into lipid raft domains of the plasma membrane, followed by the translocation of transient receptor potential calcium channel 1 (PMID:15105836)
• hTRPC1 is an important Ca(2+)-permeable channel that mediates pulmonary vasoconstriction when pulmonary artery smooth muscle cell intracellular Ca2+ stores are depleted. (PMID:15220115)
• Expression level of TRPC1 in endothelial cells is a critical determinant of Ca(2+) influx and signaling of the increase in endothelial permeability. (PMID:15347566)
• role in inhibiting 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells (PMID:15542611)
• 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)
• TRPC1, but not TRPC4, interacts with PLCgamma1 and the inositol 1,4,5-trisphosphate receptor (IP3R). (PMID:15654973)
• TRPC1 and/or TRPC5 channels serve as store-operated Ca2+ channels in A431 cells, and may function as regulators for intracellular Ca2+ signaling. (PMID:15763245)
• 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)
• TRPC1 is involved in calcium-induced differentiation of human gingival keratinocytes likely by supporting a store-operated calcium ion influx. (PMID:16283206)
• demonstrates that hTrpC1 and hTrpC4 are the most abundant TrpC mRNAs in human myometrium, with TrpC6 being the next most abundant; these isoforms may play significant roles in signal regulated calcium entry in human myometrium (PMID:16527499)
• 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)
• results indicate that TRPC1 proteins function as Ca2+ permeable channels in intestinal epithelial cells and play a critical role in the regulation of apoptosis (PMID:16551274)
• protease-activated receptor-1 has a role in calcium influx, which activates a feed-forward mechanism of TRPC1 expression via nuclear factor-kappaB activation in endothelial cells (PMID:16709572)
• Thus, these results demonstrate a crucial role of caveolin-1 scaffolding domain interaction with TRPC1 in regulating Ca2+ influx via SOC. (PMID:16822931)
• Interaction of STIM1 with endogenously expressed human canonical TRP1 (hTRPC1) upon depletion of intracellular Ca2+ stores. (PMID:16870612)
• We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD. (PMID:16899508)
• activation of TRPC1 leads to the entry to the cytoplasmic space of substantial amounts of Na+ as well as Ca2+–{REVIEW} (PMID:17217049)
• dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in activation of SOC channel in response to internal Ca2+ store depletion (PMID:17224452)
• TRPC1 has an important role in store-operated calcium channels [review] (PMID:17233611)
• Angiotensin II and subsequent NF-kappaB activation induce human coronary artery smooth muscle cell hypertrophy through an enhancement of transient receptor potential channel 1 (TRPC1) expression. (PMID:17289052)
• In human salivary gland TRPC1 regulates calcium homeostasis and may have a role in cell differentiation. (PMID:17348017)
• These results indicate that TRPC1 is a multifunctional protein able to form intracellular calcium release channels when expressed alone, and plasma membrane channels when co-expressed with TRPC4 or TRPC5, but not TRPC3 or TRPC6. (PMID:17850866)
• TRPC1-associated alpha-actinin is tyrosine phosphorylated during platelet activation. (PMID:17892531)
• TRPC1 channel expression was important for keratinocyte differentiation, as knocking out the channels (by siRNA strategy) prevented the induction of Ca(2+)-induced differentiation. (PMID:17920677)
• functional expression of TRPC1 in mammalian stretch-activated mechano-sensitive Ca(2+) permeable cation channels remains problematic (PMID:17957383)
• TRPC5 and TRPC1 are expressed in secretory fibroblast-like synoviocytes from patients with rheumatoid arthritis, and endogenous TRPC5-TRPC1 channels of the cells are activated by reduced thioredoxin (PMID:18172497)
• Dyssregulation of HNF 4 alpha and TRPC1 may be a possible molecular rationale in diabetic nephropathy. (PMID:18184923)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpc1	ENSDARG00000061203
mus_musculus	Trpc1	ENSMUSG00000032839
rattus_norvegicus	Trpc1	ENSRNOG00000054902
drosophila_melanogaster	trp	FBGN0003861
drosophila_melanogaster	trpl	FBGN0005614
drosophila_melanogaster	Trpgamma	FBGN0032593
caenorhabditis_elegans		WBGENE00006615

Paralogs (5): TRPC7 (ENSG00000069018), TRPC5 (ENSG00000072315), TRPC4 (ENSG00000133107), TRPC6 (ENSG00000137672), TRPC3 (ENSG00000138741)

Protein

Protein identifiers

Short transient receptor potential channel 1 — P48995 (reviewed: P48995)

Alternative names: Transient receptor protein 1

All UniProt accessions (3): P48995, A0A8V8TLK5, H7C508

UniProt curated annotations — full annotation on UniProt →

Function. Forms a receptor-activated non-selective calcium permeant cation channel. Forms a heteromeric ion channel with TRPC4 or TRPC5 that has reduced calcium permeability compared to the homomeric TRPC4 or TRPC5 channel. Also permeable to monovalent ions including sodium, lithium and cesium ions. Forms a receptor-activated non-selective calcium permeant cation channel. Also activated by intracellular calcium store depletion.

Subunit / interactions. Heterotetramer with TRPC4 and/or TRPC5. Forms a heteromeric ion channel with TRPC4, with a 1:3 TRPC1:TRPC4 stoichiometry. Unlike other TRP channel proteins, does not form a homomeric channel. Interacts with TRPC4AP. Interacts with ITPR3. Interacts with MX1 and RNF24. Interacts with FKBP4. Interacts with PLSCR1. Interacts with PKD2L2. Forms a heterotetramer with PKD2 with a 2:2 stoichiometry; has distinct channel properties separate from PKD2 or TRPC1 homomers alone. Interacts with isoform 2 of TRPC3.

Subcellular location. Cell membrane.

Tissue specificity. Seems to be ubiquitous.

Post-translational modifications. Activation of PRKCA induces phosphorylation of TRPC1 and subsequent Ca2+ entry into cells.

Activity regulation. May be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Also activated by intracellular calcium store depletion. Inhibited by xanthine-based inhibitor Pico145.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P48995-1	Long	yes
P48995-2	Short, TRPC1A

RefSeq proteins (13): NP_001238774, NP_001400290, NP_001400291, NP_001400292, NP_001400304, NP_001400305, NP_001400306, NP_001400307, NP_001400308, NP_001400309, NP_001400310, NP_001400311, NP_003295 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR002153	TRPC_channel	Family
IPR005457	TRPC1_channel	Family
IPR005821	Ion_trans_dom	Domain
IPR013555	TRP_dom	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00520, PF08344

Catalyzed reactions (Rhea), 4 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• Li(+)(in) = Li(+)(out) (RHEA:78551)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)

UniProt features (82 total): helix 37, topological domain 8, strand 7, turn 7, transmembrane region 6, repeat 4, binding site 4, mutagenesis site 3, chain 1, intramembrane region 1, region of interest 1, compositionally biased region 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9KHI	ELECTRON MICROSCOPY	2.7
9K4I	ELECTRON MICROSCOPY	2.84
8WPL	ELECTRON MICROSCOPY	3.04
8WPM	ELECTRON MICROSCOPY	3.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48995-F1	79.87	0.32

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 (4): 189; 193; 195; 198

Disulfide bonds (1): 571–576

Mutagenesis-validated functional residues (3):

Position	Phenotype
601	decreases permeability to calcium ions and increases permeability to cesium ions.
646	decreases permeability to calcium ions and increases permeability to cesium ions.
647	decreases permeability to calcium ions.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3295583	TRP channels
R-HSA-418890	Role of second messengers in netrin-1 signaling
R-HSA-5578775	Ion homeostasis
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

MSigDB gene sets: 242 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, AAGCCAT_MIR135A_MIR135B, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, MODULE_70, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_SEQUESTERED_CALCIUM_ION_INTO_CYTOSOL, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT

GO Biological Process (10): calcium ion transport (GO:0006816), melanin biosynthetic process (GO:0042438), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), regulation of cytosolic calcium ion concentration (GO:0051480), response to calcium ion (GO:0051592), calcium ion transmembrane transport (GO:0070588), regulation of cardiac conduction (GO:1903779), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (10): signaling receptor binding (GO:0005102), monoatomic cation channel activity (GO:0005261), calcium channel activity (GO:0005262), store-operated calcium channel activity (GO:0015279), transmembrane transporter binding (GO:0044325), metal ion binding (GO:0046872), ATPase binding (GO:0051117), inositol 1,4,5 trisphosphate binding (GO:0070679), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), cation channel complex (GO:0034703), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Stimuli-sensing channels	1
Netrin-1 signaling	1
Cardiac conduction	1
Signaling by the B Cell Receptor (BCR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
protein binding	2
metal ion transport	1
melanin metabolic process	1
secondary metabolite biosynthetic process	1
pigment biosynthetic process	1
phenol-containing compound biosynthetic process	1
release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol	1
positive regulation of calcium ion transmembrane transport	1
intracellular calcium ion homeostasis	1
response to metal ion	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
regulation of heart contraction	1
cardiac conduction	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
calcium channel activity	1
cation binding	1
enzyme 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
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPC1	STIM1	Q13586	999
TRPC1	TRPV4	Q9HBA0	996
TRPC1	ORAI1	Q96D31	995
TRPC1	PKD2	Q13563	994
TRPC1	TRPC5	Q9UL62	983
TRPC1	TRPC4	Q9UBN4	982
TRPC1	ORAI2	Q96SN7	963
TRPC1	ITPR3	Q14573	962
TRPC1	ITPR1	Q14643	959
TRPC1	STIM2	Q9P246	937
TRPC1	PKD1	P98161	903
TRPC1	ORAI3	Q9BRQ5	902
TRPC1	TRPC3	Q13507	898
TRPC1	TRPV1	Q8NER1	893
TRPC1	CACNA1C	Q13936	891

IntAct

73 interactions, top by confidence:

A	B	Type	Score
TRPC1	PKD2	psi-mi:“MI:0915”(physical association)	0.690
PKD2	TRPC1	psi-mi:“MI:0915”(physical association)	0.690
PKD2	TRPC1	psi-mi:“MI:0403”(colocalization)	0.690
TRPC1	PKD2	psi-mi:“MI:0403”(colocalization)	0.690
STIM1	TRPC1	psi-mi:“MI:0915”(physical association)	0.640
STIM1	TRPC1	psi-mi:“MI:0914”(association)	0.640
TRPC1	STIM1	psi-mi:“MI:0915”(physical association)	0.640
TRPC1	CAV1	psi-mi:“MI:0914”(association)	0.630
TRPC1	CAV1	psi-mi:“MI:0407”(direct interaction)	0.630
TRPC1	CAV1	psi-mi:“MI:0915”(physical association)	0.630
CAV1	TRPC1	psi-mi:“MI:0914”(association)	0.630
ORAI1	TRPC1	psi-mi:“MI:0915”(physical association)	0.400
TRPC1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
Trpv4	TRPC1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (42): TRPC1 (Two-hybrid), GRM1 (Affinity Capture-Western), ENKUR (Affinity Capture-Western), TRPC1 (Affinity Capture-Western), TRPC1 (Affinity Capture-Western), TRPC1 (Affinity Capture-Western), TRPC1 (Reconstituted Complex), TRPC6 (Affinity Capture-Western), TRPC3 (Affinity Capture-Western), TRPC1 (Affinity Capture-Western), TRPC1 (Affinity Capture-Western), TRPC1 (Affinity Capture-Western), TRPC1 (Reconstituted Complex), TRPC1 (Two-hybrid), TRPC1 (Reconstituted Complex)

ESM2 similar proteins: A0A1D5PXA5, O18784, O35119, O35433, O62852, P0C550, P19334, P34586, P34641, P48994, P48995, P69744, P79100, P97414, Q0JKV1, Q12324, Q5ICL9, Q61056, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q875M2, Q8GXE6, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q96L42, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9MYV9, Q9NQA5, Q9P2G1, Q9QUQ5, Q9QX01, Q9QX29

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, Q6IVV8, O54935, P18887, Q60596, Q6ZNB5, Q9ESZ0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKCD	“up-regulates activity”	TRPC1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2172 predictions. Top by Δscore:

Variant	Effect	Δscore
3:142724730:GG:G	donor_gain	1.0000
3:142724731:GG:G	donor_gain	1.0000
3:142736527:TTGTC:T	donor_gain	1.0000
3:142743584:GTA:G	donor_gain	1.0000
3:142743587:G:GG	donor_gain	1.0000
3:142748252:TTTCA:T	acceptor_loss	1.0000
3:142748253:TTCAG:T	acceptor_loss	1.0000
3:142748254:TCAGA:T	acceptor_loss	1.0000
3:142748255:CAGAA:C	acceptor_loss	1.0000
3:142748256:A:AG	acceptor_gain	1.0000
3:142748256:A:AT	acceptor_loss	1.0000
3:142748257:G:GA	acceptor_gain	1.0000
3:142748257:GAA:G	acceptor_gain	1.0000
3:142748372:G:GT	donor_gain	1.0000
3:142781025:AAGAG:A	donor_loss	1.0000
3:142781026:AGAGG:A	donor_loss	1.0000
3:142781027:GAGGT:G	donor_loss	1.0000
3:142781028:AGGTA:A	donor_loss	1.0000
3:142781029:GG:G	donor_loss	1.0000
3:142781030:GT:G	donor_loss	1.0000
3:142781031:T:G	donor_loss	1.0000
3:142792905:GTTC:G	donor_gain	1.0000
3:142792906:TTCT:T	donor_gain	1.0000
3:142802241:A:AG	acceptor_gain	1.0000
3:142802242:C:G	acceptor_gain	1.0000
3:142802243:A:AG	acceptor_gain	1.0000
3:142802243:AATT:A	acceptor_gain	1.0000
3:142802243:AATTG:A	acceptor_gain	1.0000
3:142802244:A:G	acceptor_gain	1.0000
3:142802340:CATTC:C	donor_gain	1.0000

AlphaMissense

5247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:142743543:T:C	L129P	1.000
3:142748327:G:C	A167P	1.000
3:142748328:C:A	A167D	1.000
3:142748405:T:A	C193S	1.000
3:142748405:T:C	C193R	1.000
3:142748406:G:C	C193S	1.000
3:142748411:T:C	C195R	1.000
3:142748413:C:G	C195W	1.000
3:142748420:T:A	C198S	1.000
3:142748420:T:C	C198R	1.000
3:142748421:G:A	C198Y	1.000
3:142748421:G:C	C198S	1.000
3:142748422:T:G	C198W	1.000
3:142748448:T:C	L207P	1.000
3:142777636:C:A	R213S	1.000
3:142777718:T:C	L240P	1.000
3:142777739:T:C	L247P	1.000
3:142777759:T:C	F254L	1.000
3:142777761:C:A	F254L	1.000
3:142777761:C:G	F254L	1.000
3:142780926:T:C	L286P	1.000
3:142781007:C:A	A313D	1.000
3:142784704:T:C	F321L	1.000
3:142784705:T:C	F321S	1.000
3:142784706:T:A	F321L	1.000
3:142784706:T:G	F321L	1.000
3:142784708:T:A	V322D	1.000
3:142784735:T:C	L331P	1.000
3:142785031:T:A	W430R	1.000
3:142785031:T:C	W430R	1.000

dbSNP variants (sampled 300 via entrez): RS1000237413 (3:142726031 CAG>C), RS1000272023 (3:142752507 A>G), RS1000447443 (3:142759967 G>T), RS1000474532 (3:142775447 C>T), RS1000497963 (3:142785596 G>A), RS1000565540 (3:142753866 G>A,C), RS1000574911 (3:142727515 A>G), RS1000585509 (3:142733170 A>G), RS1000597924 (3:142754387 A>G), RS1000723895 (3:142804157 T>C), RS1000822080 (3:142782341 A>G), RS1000834216 (3:142731627 G>A,C,T), RS1000992539 (3:142734547 G>A), RS1001007080 (3:142805475 T>C), RS1001089176 (3:142797784 C>T)

Disease associations

OMIM: gene MIM:602343 | disease phenotypes: MIM:145600

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), malignant hyperthermia, susceptibility to, 1 (MONDO:0007783), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Familial prostate cancer (Orphanet:1331), Malignant hyperthermia of anesthesia (Orphanet:423)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C535694	Malignant hyperthermia susceptibility type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4296083 (PROTEIN COMPLEX), CHEMBL4523660 (PROTEIN COMPLEX), CHEMBL4523661 (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: 50 (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
CHEMBL4466522	ZERENCOTREP	2	50

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)

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.48	IC50	0.033	nM	ZERENCOTREP
9.72	IC50	0.19	nM	ZERENCOTREP
7.21	IC50	62	nM	CHEMBL4450705
6.52	IC50	300	nM	CHEMBL101896
6.30	IC50	500	nM	CHEMBL4177187
6.22	IC50	600	nM	CHEMBL4162723
5.51	IC50	3100	nM	CHEMBL4162062
5.36	IC50	4400	nM	CHEMBL4172741

PubChem BioAssay actives

8 with measured affinity, of 95 total; 7 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
7-[(4-chlorophenyl)methyl]-1-(3-hydroxypropyl)-3-methyl-8-[3-(trifluoromethoxy)phenoxy]purine-2,6-dione	1578709: Inhibition of human TRPC4/human TRPC1 expressed in HEK293 cells assessed as reduction in englerin A-induced calcium entry incubated for 30 mins by Fluo-4AM dye based fluorescence assay	ic50	<0.0001	uM
[(1R,2R,5R,6R,7S,8S,10R)-10-(2-hydroxyethoxy)-1,5-dimethyl-8-propan-2-yl-11-oxatricyclo[6.2.1.02,6]undecan-7-yl] (E)-3-phenylprop-2-enoate	1578692: Antagonist activity at TRPC4/TRPC1 in human A498 cells assessed as reduction in englerin A-induced calcium entry preincubated for 30 mins followed by englerin A addition by fluorescence method	ic50	0.0620	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
ethyl 1-[4-(2,3,3-trichloroprop-2-enoylamino)phenyl]-5-(trifluoromethyl)pyrazole-4-carboxylate	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	0.5000	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
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
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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, affects expression	4
Acetaminophen	decreases expression, increases expression	2
Nickel	decreases expression	2
Cyclosporine	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
perfluorooctanoic acid	increases expression	1
fasudil	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
Y 27632	decreases reaction, increases expression	1
abrine	increases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sildenafil Citrate	increases expression, decreases reaction	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiloride	affects binding, decreases activity	1
Atrazine	decreases expression	1
Calcium	increases import	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	affects response to substance	1
Estradiol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	decreases reaction, increases import	1
Methamphetamine	increases expression	1
Methyl Methanesulfonate	increases expression	1
Oxygen	decreases reaction, increases expression, affects reaction	1
Dronabinol	increases response to substance	1

ChEMBL screening assays

19 unique, capped per target: 15 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4158679	Binding	Modulation of TRPC1/TRPC3/STIM1/Orai1 in HEK cells assessed as induction of store-operated calcium entry by measuring residual activity at 10 uM preincubated for 30 mins followed by tBhQ-mediated Ca2+ depletion and Ca2+ re-addition to extra	Pyrtriazoles, a Novel Class of Store-Operated Calcium Entry Modulators: Discovery, Biological Profiling, and in Vivo Proof-of-Concept Efficacy in Acute Pancreatitis. — J Med Chem
CHEMBL4622714	ADMET	Agonist activity at human TRPC4/TRPC1 expressed in HEK293 Tet cells assessed as increase in intracellular calcium level at 1 uM measured at 5 secs interval for 300 secs by Fura-2AM dye based fluorescence assay	Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1ZG	Abcam A-549 TRPC1 KO	Cancer cell line	Male
CVCL_D2DG	Abcam HCT 116 TRPC1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer