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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TRPC3
transient receptor potential cation channel subfamily C member 3
Chromosome 4 · 4q27
NCBI Gene: 7222Ensembl: ENSG00000138741.12HGNC: HGNC:12335UniProt: Q13507
159PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
calcium channel activityresponse to ATPresponse to calcium ioncalcium ion transmembrane transportSpinocerebellar ataxia type 41atrial fibrillationatrial flutterneurodegenerative disease
✦AI Summary

TRPC3 is a calcium-permeable non-selective cation channel that forms receptor-activated heterotetrameric complexes 1. It functions as a controller of intracellular calcium homeostasis through both inhibitory and activating calcium-binding sites that couple calcium concentration to channel activity 2. TRPC3 is activated via phospholipase C signaling pathways and diacylglycerol, particularly when responding to G-protein coupled receptor and receptor tyrosine kinase stimulation 3. The channel regulates ER-mitochondria calcium transfer, with downregulation promoting mitochondrial calcium overload and cellular senescence 4. TRPC3 is broadly expressed in pancreatic acinar cells, ductal epithelium, and endocrine islet cells 5, as well as thyroid follicular cells and C-cells 6. Functionally, TRPC3 mediates mechanical pain hypersensitivity through enhanced nociceptor excitability and spinal synaptic transmission via bradykinin-induced BDNF secretion 7. In cardiac tissue, TRPC3 interacts with NADPH oxidase 2 under hypoxic stress to regulate cardiac remodeling 8. Pathologically, TRPC3 mutations associate with spinocerebellar ataxia 41, while TRPC3 dysfunction contributes to cellular senescence-associated pro-tumoral inflammation.

Sources cited
1
TRPC3 contains inhibitory and activating calcium-binding sites that regulate channel activity
PMID: 35051376
2
TRPC3 controls mitochondrial calcium load and is downregulated in cellular senescence
PMID: 35177596
3
TRPC3 is expressed in pancreatic acinar cells, ductal epithelium, and islet cells
PMID: 38870712
4
TRPC channels including TRPC3 are activated by phospholipase C signaling and diacylglycerol
PMID: 17217055
5
TRPC3 interacts with NADPH oxidase 2 to mediate cardiac remodeling under hypoxic stress
PMID: 30298191
6
TRPC3/6 mediate mechanical pain hypersensitivity via nociceptor excitability and spinal synaptic transmission
PMID: 39340833
7
TRPC3 is expressed in human thyroid follicular cells and C-cells
PMID: 39740284
8
TRPC3 forms a bell-shaped tetrameric architecture with extensive inter-subunit interactions
PMID: 29700422
Disease Associationsⓘ21
Spinocerebellar ataxia type 41Open Targets
0.62Moderate
atrial fibrillationOpen Targets
0.38Weak
atrial flutterOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.33Weak
Myocardial IschemiaOpen Targets
0.31Weak
heart failureOpen Targets
0.30Weak
type 1 diabetes mellitusOpen Targets
0.30Weak
chronic obstructive pulmonary diseaseOpen Targets
0.29Weak
cardiac arrhythmiaOpen Targets
0.28Weak
placenta praeviaOpen Targets
0.21Weak
essential tremorOpen Targets
0.11Weak
hypothyroidismOpen Targets
0.10Weak
neoplasmOpen Targets
0.09Suggestive
actinic keratosisOpen Targets
0.09Suggestive
psoriasisOpen Targets
0.08Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
bronchopulmonary dysplasiaOpen Targets
0.07Suggestive
subarachnoid hemorrhageOpen Targets
0.07Suggestive
triple-negative breast cancerOpen Targets
0.07Suggestive
ovarian cancerOpen Targets
0.07Suggestive
Spinocerebellar ataxia 41UniProt
Pathogenic Variants1
NM_001130698.2(TRPC3):c.1419del (p.Val474fs)Pathogenic
Spinocerebellar ataxia type 41
★☆☆☆2021→ Residue 474
View on ClinVar ↗
Related Genes
BMPR2Protein interaction96%STIM1Protein interaction96%TRPM4Protein interaction94%CALM3Protein interaction94%KAT5Protein interaction94%CALML5Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Lung
94%
Heart
38%
Ovary
31%
Liver
13%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
TRPC3BMPR2STIM1TRPM4CALM3KAT5CALML5
PROTEIN STRUCTURE
Preparing viewer…
PDB7DXB · 2.70 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.75LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.59 [0.47–0.75]
RankingsWhere TRPC3 stands among ~20K protein-coding genes
  • #2,838of 20,598
    Most Researched159 · top quartile
  • #4,768of 5,498
    Most Pathogenic Variants1
  • #5,945of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedTRPC3
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites.
PMID: 35051376
Neuron · 2022
1.00
2
TRPC3 shapes the ER-mitochondria Ca
PMID: 35177596
Nat Commun · 2022
0.90
3
Distribution of TRPC3 and TRPC6 in the human exocrine and endocrine pancreas.
PMID: 38870712
Pathol Res Pract · 2024
0.80
4
TRPC7.
PMID: 17217055
Handb Exp Pharmacol · 2007
0.70
5
Evaluation of immunohistochemical TRPC3 and TRPC6 expression patterns in human endometriosis.
PMID: 39689787
Ann Anat · 2025
0.64