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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TRPC5
transient receptor potential cation channel subfamily C member 5
Chromosome X · Xq23
NCBI Gene: 7224Ensembl: ENSG00000072315.4HGNC: HGNC:12337UniProt: Q9UL62
86PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedIon ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranecalcium channel complexcalcium channel activityprotein bindingIntellectual disabilitycolorectal carcinomabreast cancerobesity
✦AI Summary

TRPC5 is a calcium-permeable cation channel predominantly expressed in the central nervous system, including the hippocampus, cerebellum, and amygdala, with restricted peripheral expression in the kidney and cardiovascular system 1. As a homotetrameric or heteromeric channel (particularly with TRPC1), TRPC5 is activated by receptors coupled to Gq and phospholipase C, G proteins, and diverse stimuli including nitric oxide, lysophospholipids, and cold 123. TRPC5 regulates calcium homeostasis and operates through partnerships with approximately 60 proteins, including calmodulin and IP3 receptors 1. Clinically, TRPC5 loss-of-function mutations on chromosome X cause severe neuropsychiatric phenotypes: male carriers develop obesity, anxiety, and autism-like behaviors, while female carriers experience postpartum depression with impaired maternal care 4. TRPC5 specifically functions in oxytocin neurons of the hypothalamic paraventricular nucleus to regulate innate behaviors including food seeking and maternal care 4. Beyond neurobiology, TRPC5 contributes to cardiovascular disease pathogenesis through regulation of endothelial and smooth muscle cell calcium dynamics, oxidative stress, and apoptosis 5. TRPC5 also mediates cold sensation in somatosensory neurons 6. The channel represents a promising therapeutic target for anxiety, depression, pain disorders, and cardiovascular diseases 72.

Sources cited
1
TRPC5 structure, expression pattern, activation mechanisms, protein interactions, and biological functions including neurotransmission and axon guidance
PMID: 24756705
2
TRPC5 loss-of-function mutations cause obesity, anxiety, autism in males and postpartum depression in females through effects on oxytocin neurons
PMID: 38959890
3
Cryo-EM structure of human TRPC1/C5 heteromer and its potential as therapeutic target for anxiety and depression
PMID: 41372144
4
Direct interactions between TRPC5 and G proteins (Gαi3) in GPCR signaling
PMID: 41258080
5
TRPC5 roles in cardiovascular disease through calcium dynamics, oxidative stress, and apoptosis regulation
PMID: 33792254
6
TRPC5 involvement in thermosensation in somatosensory neurons and skin tissues
PMID: 39289270
7
TRPC5 as therapeutic target for pain relief
PMID: 38471384
Disease Associationsⓘ20
Intellectual disabilityOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
obesityOpen Targets
0.08Suggestive
primary ovarian insufficiencyOpen Targets
0.08Suggestive
papillary thyroid carcinomaOpen Targets
0.07Suggestive
46,XX gonadal dysgenesisOpen Targets
0.07Suggestive
arthritisOpen Targets
0.07Suggestive
HypoglycemiaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
premature ovarian failure 23Open Targets
0.06Suggestive
Familial hyperprolactinemiaOpen Targets
0.06Suggestive
familial hyperprolactinemiaOpen Targets
0.06Suggestive
premature ovarian failure 1Open Targets
0.06Suggestive
Ehlers-Danlos syndromeOpen Targets
0.06Suggestive
premature ovarian failure 24Open Targets
0.06Suggestive
premature ovarian failure 22Open Targets
0.06Suggestive
Non-acquired premature ovarian failureOpen Targets
0.06Suggestive
cholestasisOpen Targets
0.06Suggestive
hyperprolactinemiaOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRPV4Protein interaction97%STIM1Protein interaction97%CACNA1GProtein interaction93%CACNA1IProtein interaction93%CACNA1HProtein interaction92%BMPR2Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Liver
48%
Bone Marrow
1%
Ovary
1%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
TRPC5TRPV4STIM1CACNA1GCACNA1ICACNA1HBMPR2
PROTEIN STRUCTURE
Preparing viewer…
PDB9GKB · 2.32 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.28Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.16 [0.10–0.28]
RankingsWhere TRPC5 stands among ~20K protein-coding genes
  • #5,581of 20,598
    Most Researched86
  • #977of 17,882
    Most Constrained (LOEUF)0.28 · top 10%
Genes detectedTRPC5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
TRPC5.
PMID: 24756705
Handb Exp Pharmacol · 2014
1.00
2
DogCatcher allows loop-friendly protein-protein ligation.
PMID: 34324879
Cell Chem Biol · 2022
0.90
3
Targeting TRP channels for pain relief: A review of current evidence from bench to bedside.
PMID: 38471384
Curr Opin Pharmacol · 2024
0.80
4
TRPC5 in cardiovascular diseases.
PMID: 33792254
Rev Cardiovasc Med · 2021
0.70
5
Molecular architecture of the human TRPC1/C5 heteromeric channel.
PMID: 41372144
Nat Commun · 2025
0.60