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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TRPA1
transient receptor potential cation channel subfamily A member 1
Chromosome 8 · 8q21.11
NCBI Gene: 8989Ensembl: ENSG00000104321.12HGNC: HGNC:497UniProt: O75762
240PubMed Papers
21Diseases
4Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein homotetramerizationcellular response to hydrogen peroxidecalcium ion transmembrane transportresponse to coldfamilial episodic pain syndrome with predominantly upper body involvementarthritisCoughPain
✦AI Summary

TRPA1 is a calcium-permeable nonselective cation channel functioning primarily as a polymodal chemosensor and nociceptor 1. It mediates pain detection through activation by structurally diverse stimuli including electrophilic compounds (allylthiocyanate, cinnamaldehyde) and pro-inflammatory mediators like bradykinin 2, as well as non-electrophilic agonists such as cannabinoids and menthol 1. TRPA1 activation causes calcium and sodium influx, triggering membrane depolarization and neuropeptide release in sensory neurons 1. Beyond nociception, TRPA1 participates in cold sensation, though mammalian thermosensitivity remains controversial, while insect and bird variants demonstrate heat-activation 3. TRPA1 is expressed in nociceptive sensory neurons, keratinocytes, mast cells, and other immune cells, where it potentiates cutaneous neurogenic inflammation 4. Clinically, TRPA1 dysregulation contributes to chemotherapy-induced peripheral neuropathy, asthma, and chr8 pain conditions 567. Recent evidence reveals TRPA1 in renal tubular cells suppresses diabetic kidney disease progression via MAPK-TGF-β1 pathway inhibition 8. TRPA1 antagonists show therapeutic promise for pain management and airway inflammation 6, representing a novel drug target for neuropathic and inflammatory conditions.

Sources cited
1
TRPA1 is a nonselective cation channel permeable to Ca2+, Na+, and K+; activated by electrophiles, oxidants, and pro-inflammatory agents; also activated by non-electrophilic compounds including menthol and cannabinoids
PMID: 24756722
2
TRPA1 mediates response to bradykinin and pungent irritants from mustards and garlic; contains ankyrin repeats and six membrane-spanning domains; highly conserved across animal kingdom
PMID: 17217068
3
TRPA1 is expressed in sensory neurons, keratinocytes, mast cells, dendritic cells, and endothelial cells; participates in cutaneous neurogenic inflammation and pain signaling
PMID: 28364279
4
TRPA1 is linked to chemotherapy-induced peripheral neuropathy from oxaliplatin; Sigma-1 receptor antagonists modulate TRPA1 trafficking and function to prevent neuropathy
PMID: 35871491
5
TRPA1 agonists are elevated in asthmatic airways; TRPA1 antagonist GDC-0334 reduces airway inflammation and hyperreactivity in preclinical and clinical studies
PMID: 33620419
6
TRPA1 mediates chronic pain through oxidative stress and Schwann cell signaling; TRPA1 antagonists represent a novel class of analgesics
PMID: 32838583
7
TRPA1 temperature sensitivity varies across species; insect and bird TRPA1 show heat-activation; mammalian TRPA1 thermosensitivity remains controversial with emerging evidence of bimodal response
PMID: 39951922
8
TRPA1 expression in renal tubular cells suppresses diabetic kidney disease progression by inhibiting MAPK-TGF-β1 fibrotic pathway
PMID: 38072665
Disease Associationsⓘ21
familial episodic pain syndrome with predominantly upper body involvementOpen Targets
0.66Moderate
arthritisOpen Targets
0.60Moderate
CoughOpen Targets
0.60Moderate
PainOpen Targets
0.60Moderate
Back painOpen Targets
0.60Moderate
pharyngitisOpen Targets
0.59Moderate
common coldOpen Targets
0.59Moderate
sprainOpen Targets
0.59Moderate
PruritusOpen Targets
0.58Moderate
Nasal congestionOpen Targets
0.57Moderate
sunburnOpen Targets
0.55Moderate
MyalgiaOpen Targets
0.55Moderate
injuryOpen Targets
0.50Moderate
Oral ulcerOpen Targets
0.50Moderate
herpes labialisOpen Targets
0.50Moderate
familial episodic pain syndromeOpen Targets
0.49Moderate
HeadacheOpen Targets
0.46Moderate
burnOpen Targets
0.46Moderate
frozen shoulderOpen Targets
0.46Moderate
osteoarthritisOpen Targets
0.41Moderate
Episodic pain syndrome, familial, 1UniProt
Pathogenic Variants1
NM_007332.3(TRPA1):c.2564A>G (p.Asn855Ser)Pathogenic
Familial episodic pain syndrome with predominantly upper body involvement
☆☆☆☆2010→ Residue 855
View on ClinVar ↗
Drug Targets4
BUTAMBENUNKNOWN
Transient receptor potential cation channel subfamily A member 1 inhibitor
BUTAMBEN PICRATEUNKNOWN
Transient receptor potential cation channel subfamily A member 1 inhibitor
GRC-17536Phase II
Transient receptor potential cation channel subfamily A member 1 antagonist
Pain
MENTHOLApproved
Transient receptor potential cation channel subfamily M member 8 opener
pharyngitis
Related Genes
PRKCEProtein interaction95%NGFProtein interaction92%HIF1ANProtein interaction90%TRPV4Protein interaction85%TRPM3Protein interaction81%SCG3Protein interaction81%
Tissue Expression6 tissues
Brain
100%
Ovary
19%
Lung
10%
Liver
6%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
TRPA1PRKCENGFHIF1ANTRPV4TRPM3SCG3
PROTEIN STRUCTURE
Preparing viewer…
PDB6HC8 · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.06LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.88 [0.74–1.06]
RankingsWhere TRPA1 stands among ~20K protein-coding genes
  • #1,639of 20,598
    Most Researched240 · top 10%
  • #834of 1,025
    FDA-Approved Drug Targets1
  • #4,701of 5,498
    Most Pathogenic Variants1
  • #10,698of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedTRPA1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
TRPA1 as a therapeutic target for nociceptive pain.
PMID: 32838583
Expert Opin Ther Targets · 2020
1.00
2
TRPA1.
PMID: 24756722
Handb Exp Pharmacol · 2014
0.90
3
TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization.
PMID: 28364279
Protein Cell · 2017
0.80
4
TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy.
PMID: 35871491
Brain · 2023
0.70
5
A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment.
PMID: 33620419
J Exp Med · 2021
0.60