TRPC7

Summary

TRPC7 (transient receptor potential cation channel subfamily C member 7, HGNC:20754) is a protein-coding gene on chromosome 5q31.1, encoding Short transient receptor potential channel 7 (Q9HCX4). Forms a receptor-activated non-selective calcium permeant cation channel.

Predicted to enable inositol 1,4,5 trisphosphate binding activity and store-operated calcium channel activity. Predicted to be involved in calcium ion transmembrane transport; regulation of cytosolic calcium ion concentration; and single fertilization. Predicted to be located in membrane; nuclear envelope; and perinuclear region of cytoplasm. Predicted to be part of cation channel complex. Predicted to be active in plasma membrane. Implicated in lung cancer.

Source: NCBI Gene 57113 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 109 total
• Druggable target: yes
• MANE Select transcript: NM_020389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20754
Approved symbol	TRPC7
Name	transient receptor potential cation channel subfamily C member 7
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000069018
Ensembl biotype	protein_coding
Entrez	57113

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000352189, ENST00000378459, ENST00000502753, ENST00000503275, ENST00000509288, ENST00000513104, ENST00000514963

RefSeq mRNA: 4 — MANE Select: NM_020389 NM_001167576, NM_001167577, NM_001376901, NM_020389

CCDS: CCDS47267, CCDS54905, CCDS54906, CCDS93787

Canonical transcript exons

ENST00000513104 — 12 exons

Exon	Start	End
ENSE00002055508	136212745	136213604
ENSE00002077005	136356608	136357385
ENSE00002351005	136274673	136274837
ENSE00002410827	136315597	136315779
ENSE00003513924	136216200	136216275
ENSE00003526390	136226034	136226255
ENSE00003581155	136266220	136266436
ENSE00003583424	136247471	136247735
ENSE00003617190	136251649	136251882
ENSE00003658857	136231354	136231549
ENSE00003679689	136225274	136225354
ENSE00003899944	136365253	136365545

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 95.49.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.00	gold quality
secondary oocyte	CL:0000655	76.98	gold quality
cortical plate	UBERON:0005343	61.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.28	gold quality
adult mammalian kidney	UBERON:0000082	61.12	gold quality
oocyte	CL:0000023	60.79	gold quality
rectum	UBERON:0001052	57.27	gold quality
kidney	UBERON:0002113	53.70	gold quality
duodenum	UBERON:0002114	50.75	gold quality
right testis	UBERON:0004534	50.69	gold quality
adenohypophysis	UBERON:0002196	50.43	gold quality
hypothalamus	UBERON:0001898	50.40	gold quality
testis	UBERON:0000473	49.87	gold quality
left testis	UBERON:0004533	49.72	gold quality
pituitary gland	UBERON:0000007	49.62	gold quality
mucosa of transverse colon	UBERON:0004991	48.20	gold quality
transverse colon	UBERON:0001157	48.12	gold quality
gall bladder	UBERON:0002110	47.17	gold quality
putamen	UBERON:0001874	47.04	gold quality
Brodmann (1909) area 46	UBERON:0006483	46.99	gold quality
colonic epithelium	UBERON:0000397	45.56	gold quality
nucleus accumbens	UBERON:0001882	45.53	gold quality
small intestine	UBERON:0002108	45.34	gold quality
islet of Langerhans	UBERON:0000006	44.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	44.12	gold quality
prefrontal cortex	UBERON:0000451	44.03	gold quality
metanephros cortex	UBERON:0010533	44.02	gold quality
cortex of kidney	UBERON:0001225	43.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting TRPC7, 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-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457
HSA-MIR-6774-3P	89.14	65.20	68

Literature-anchored findings (GeneRIF, showing 11)

• Cloning and functional expression of human short TRP7, a candidate protein for store-operated Ca2+ influx (PMID:11805119)
• can be activated by both receptor- and store-operated modes in the same cell. (PMID:15342342)
• 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)
• in B-lymphocytes, TRPC7 appears to participate in the formation of ion channels that could be activated by phospholipase C-linked receptors (PMID:16123040)
• activation of both muscarinic and purinergic receptors via a common DAG-dependent link opens Ca(2+)-permeable TRPC7 channels (PMID:16741513)
• the physiological importance of TRPC7 in the native environment remains elusive, TRPC7 would play important roles in Ca2+ signaling pathway–{REVIEW} (PMID:17217055)
• Expression and activity of TRPM7 is modulated by extracellular Mg2+ and Ca2+ availability, indicating that TRPM7 channels are involved in intracellular ion homeostasis and proliferation of osteoblasts. (PMID:18021175)
• heteromeric cation channels comprised of the TRPP2 mutant and the TRPC3 or TRPC7 protein induce enhanced receptor-activated Ca(2+) influx that may lead to dysregulated cell growth in ADPKD (PMID:19812035)
• Phosphorylation of transient receptor potential cation channel subfamily C member 7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. (PMID:21402151)
• A fundamental role for PI(4,5)P2 was identified in the regulation of TRPC7 and TRPC6. (PMID:24470487)
• Nociceptive transient receptor potential canonical 7 (TRPC7) mediates aging-associated tumorigenesis induced by ultraviolet B. (PMID:31755176)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpc7a	ENSDARG00000027523
danio_rerio	trpc7b	ENSDARG00000079469
mus_musculus	Trpc7	ENSMUSG00000021541
rattus_norvegicus	Trpc7	ENSRNOG00000012727
caenorhabditis_elegans		WBGENE00006614

Paralogs (5): TRPC5 (ENSG00000072315), TRPC4 (ENSG00000133107), TRPC6 (ENSG00000137672), TRPC3 (ENSG00000138741), TRPC1 (ENSG00000144935)

Protein

Protein identifiers

Short transient receptor potential channel 7 — Q9HCX4 (reviewed: Q9HCX4)

Alternative names: Transient receptor protein 7

All UniProt accessions (4): Q9HCX4, A1A4Z5, Q70T24, Q70T25

UniProt curated annotations — full annotation on UniProt →

Function. Forms a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG). May also be activated by intracellular calcium store depletion.

Subunit / interactions. Interacts with MX1 and RNF24. Interacts (via ANK-repeat domains) with PRKG1.

Subcellular location. Cell membrane. Nucleus envelope.

Post-translational modifications. Phosphorylation by PRKG1 at Thr-15 negatively regulates TRPC7 activity.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC7 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HCX4-1	1	yes
Q9HCX4-2	2
Q9HCX4-3	3

RefSeq proteins (4): NP_001161048, NP_001161049, NP_001363830, NP_065122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR002153	TRPC_channel	Family
IPR005463	TRPC7_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 (26 total): topological domain 7, transmembrane region 6, repeat 4, splice variant 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCX4-F1	81.97	0.41

Functional residue map

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

Post-translational modifications (1): 15

Glycosylation sites (1): 514

Function

Pathways and Gene Ontology

Reactome pathways

4 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

MSigDB gene sets: 87 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_TRANSITION_METAL_ION_TRANSPORT, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, GOBP_REGULATION_OF_CYTOSOLIC_CALCIUM_ION_CONCENTRATION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_FERTILIZATION, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_NUCLEAR_ENVELOPE, chr5q31, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (8): manganese ion transport (GO:0006828), single fertilization (GO:0007338), regulation of cytosolic calcium ion concentration (GO:0051480), calcium ion transmembrane transport (GO:0070588), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

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

GO Cellular Component (6): nuclear envelope (GO:0005635), plasma membrane (GO:0005886), cation channel complex (GO:0034703), perinuclear region of cytoplasm (GO:0048471), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cellular anatomical structure	2
transition metal ion transport	1
fertilization	1
intracellular calcium ion homeostasis	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
calcium channel activity	1
anion binding	1
alcohol binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	1
nucleus	1
endomembrane system	1
organelle envelope	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPC7	TAC1	P20366	885
TRPC7	TXNDC17	Q9BRA2	772
TRPC7	GNRH2	O43555	764
TRPC7	TAC3	Q9UHF0	669
TRPC7	GRP	P07491	665
TRPC7	TACR1	P25103	644
TRPC7	GNRH1	P01148	622
TRPC7	TRPC4	Q9UBN4	598
TRPC7	DLD	P09622	591
TRPC7	TACR2	P21452	571
TRPC7	MDM4	O15151	560
TRPC7	THRB	P10828	525
TRPC7	PYCR1	P32322	508
TRPC7	SELL	P14151	508
TRPC7	TACR3	P29371	507
TRPC7	NMB	P08949	507

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TRPC7	MX1	psi-mi:“MI:0915”(physical association)	0.400
TRPC3	SEC24A	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): FKBP1A (Affinity Capture-Western), TRPC7 (Affinity Capture-Western), TRPC7 (FRET), TRPC7 (FRET), TRPC7 (FRET), TRPC7 (Reconstituted Complex), TRPC7 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3S9V6, A0M8U1, A6NH52, E1BWM5, O35089, P13666, P86050, Q00765, Q0VCK9, Q0X0A5, Q1RLU8, Q29S14, Q2PG42, Q3KNM2, Q3ZC24, Q5BJU5, Q5M7T4, Q5R9I4, Q5R9K4, Q5RE33, Q5T4T1, Q5ZJ41, Q5ZJD7, Q6DD32, Q6GM44, Q6NYF1, Q6P360, Q6PI25, Q7TQ48, Q86TD4, Q8C407, Q8L5Y9, Q8MK44, Q8R1Z9, Q91ZQ0, Q940S0, Q96GC9, Q99K70, Q99KU0, Q9BSR8

Diamond homologs: A2A259, H2LRU7, O35245, Q13563, Q4GZT3, Q6IVV8, Q9HCX4, Q9JLG4, Q9NZM6, Q9P0L9, Q9U1S7, Q9WVC5, O18784, O35119, O62826, O62852, P19334, P34586, P48994, P48995, P79100, Q13507, Q61056, Q61143, Q9JMI9, Q9MYV9, Q9MYW0, Q9QUQ5, Q9QX01, Q9QX29, Q9QZC1, Q9R244, Q9R283, Q9TUN9, Q9UBN4, Q9UL62, Q9VJJ7, Q9Y210, O54935, P18887

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKG1	“up-regulates activity”	TRPC7	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

5713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:136213556:A:G	L823P	1.000
5:136213565:C:G	R820P	1.000
5:136213566:G:T	R820S	1.000
5:136213568:A:G	L819P	1.000
5:136213570:G:C	S818R	1.000
5:136213570:G:T	S818R	1.000
5:136213572:T:G	S818R	1.000
5:136213575:A:G	S817P	1.000
5:136213577:A:C	I816S	1.000
5:136213577:A:T	I816N	1.000
5:136213580:T:A	D815V	1.000
5:136213580:T:C	D815G	1.000
5:136213580:T:G	D815A	1.000
5:136213581:C:G	D815H	1.000
5:136213583:T:G	Q814P	1.000
5:136213585:C:A	K813N	1.000
5:136213585:C:G	K813N	1.000
5:136213587:T:C	K813E	1.000
5:136213589:A:C	I812S	1.000
5:136213589:A:G	I812T	1.000
5:136213589:A:T	I812N	1.000
5:136216249:T:A	R790S	1.000
5:136216249:T:G	R790S	1.000
5:136216259:A:G	L787P	1.000
5:136226215:A:G	L694P	1.000
5:136226222:C:G	A692P	1.000
5:136226224:C:G	R691P	1.000
5:136226229:G:C	F689L	1.000
5:136226229:G:T	F689L	1.000
5:136226230:A:G	F689S	1.000

dbSNP variants (sampled 300 via entrez): RS1000037447 (5:136302254 A>G), RS1000058081 (5:136360790 A>C,G), RS1000060337 (5:136348748 C>G,T), RS1000088081 (5:136263281 A>G), RS1000110806 (5:136303370 C>T), RS1000119740 (5:136345827 T>C), RS1000131524 (5:136360560 G>A), RS1000157940 (5:136322607 G>C), RS1000181013 (5:136304230 T>A,C), RS1000190480 (5:136252743 T>G), RS1000194704 (5:136266080 A>T), RS1000198858 (5:136220525 C>T), RS1000214949 (5:136227460 G>A), RS1000262063 (5:136311413 G>A), RS1000301306 (5:136213946 C>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105799 (SINGLE PROTEIN)

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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
SH045	Channel blocker	6.66	pIC50
SAR7334	Channel blocker	6.65	pIC50
larixyl acetate	Inhibition	6.3	pIC50
BI 749327	Antagonist	6.3	pIC50
pyrazolopyrimidine 4n	Activation	6.05	pIC50

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	EC50	90	nM	CHEMBL4085233
6.67	EC50	213	nM	CHEMBL4060387
6.65	IC50	226	nM	CHEMBL4129809
6.50	EC50	314	nM	CHEMBL4060400
6.30	EC50	497	nM	CHEMBL1496110
5.95	EC50	1130	nM	CHEMBL1496110
5.47	IC50	3400	nM	CHEMBL5561986

PubChem BioAssay actives

7 with measured affinity, of 15 total; 6 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
ethyl 4-[2-methyl-7-oxo-3-[4-(trifluoromethyl)phenyl]-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447383: Agonist activity at human TRPC7 expressed in HEK293 cells assessed as increase in intracellular calcium level measured for 2.5 mins in presence of 2 mM Ca2+ by Fluo8-AM dye-based fluorescence assay	ec50	0.0900	uM
benzyl 4-[3-(4-chlorophenyl)-2-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447383: Agonist activity at human TRPC7 expressed in HEK293 cells assessed as increase in intracellular calcium level measured for 2.5 mins in presence of 2 mM Ca2+ by Fluo8-AM dye-based fluorescence assay	ec50	0.2130	uM
4-[[(1R,2R)-2-[(3R)-3-aminopiperidin-1-yl]-2,3-dihydro-1H-inden-1-yl]oxy]-3-chlorobenzonitrile	1578752: Inhibition of human TRPC7 expressed in HEK293 cells assessed as reduction in OAG-induced calcium influx after 10 mins by fluo-4/AM dye based FLIPR assay	ic50	0.2260	uM
benzyl 4-[3-(4-fluorophenyl)-2-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447383: Agonist activity at human TRPC7 expressed in HEK293 cells assessed as increase in intracellular calcium level measured for 2.5 mins in presence of 2 mM Ca2+ by Fluo8-AM dye-based fluorescence assay	ec50	0.3140	uM
ethyl 4-[3-(4-fluorophenyl)-2-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	1447383: Agonist activity at human TRPC7 expressed in HEK293 cells assessed as increase in intracellular calcium level measured for 2.5 mins in presence of 2 mM Ca2+ by Fluo8-AM dye-based fluorescence assay	ec50	0.4970	uM
2-[2-aminoethyl(naphthalen-2-ylmethyl)amino]-N-(4-hydroxyphenyl)-1,3-thiazole-4-carboxamide	2079975: Antagonist activity at human TRPC7 stably expressed in HEK293 cells inhibition of calcium influx by calcium fluorescence assay	ic50	3.4000	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
aristolochic acid I	increases expression	1
microcystin RR	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Dinoprostone	increases response to substance	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4015194	Binding	Agonist activity at human TRPC7 expressed in HEK293 cells assessed as increase in membrane depolarization measured for 2.5 mins in presence of 2 mM Ca2+ by FLIPR membrane potential dye-based fluorescence assay	Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels. — J Med Chem

Clinical trials (associated diseases)

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