TRPA1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the TRPA1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | TRPA1 |
|---|---|
| Full Name | Transient receptor potential cation channel subfamily A member 1 |
| Gene Type | protein coding |
| Chromosomal Location | 8q21.11 |
| NCBI Gene ID | 8989 ncbi.nlm.nih.gov/gene/8989 |
| Ensembl ID | ENSG00000104325 |
| UniProt ID | O75762 |
| OMIM ID | 604775 |
| HGNC ID | 17116 |
| Aliases | ANKTM1, FEPS1, TRPA1 |
Description
The TRPA1 gene encodes a member of the transient receptor potential (TRP) family of ion channels. TRPA1 is a calcium-permeable, non-selective cation channel that is activated by various chemical irritants, cold temperatures, and inflammatory mediators. It is primarily expressed in sensory neurons and plays a critical role in pain sensation, neurogenic inflammation, and nociception. TRPA1 is involved in the detection of environmental irritants such as mustard oil, cinnamaldehyde, and acrolein, and is implicated in pain hypersensitivity and chronic pain conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Episodic pain syndrome, familial, 1 (FEPS1) | Gain-of-function mutations in TRPA1 lead to hyperexcitability of sensory neurons, causing spontaneous pain episodes. | OMIM: 604775; ClinVar: Pathogenic variants (e.g., p.Asn855Ser) associated with FEPS1. |
| Chronic pain disorders (e.g., neuropathic pain, inflammatory pain) | TRPA1 activation by inflammatory mediators and oxidative stress contributes to pain sensitization and chronic pain. | PubMed: Numerous studies; ClinVar: Variants of uncertain significance in pain cohorts. |
| Asthma and airway inflammation | TRPA1 activation by environmental irritants induces neurogenic inflammation in airways, contributing to asthma pathophysiology. | PubMed: Animal models and human studies; OMIM: Not directly listed, but TRPA1 is a therapeutic target. |
| Migraine | TRPA1 activation by endogenous or exogenous triggers may mediate meningeal nociception and migraine pain. | PubMed: Preclinical studies; ClinVar: No direct germline variants, but expression in trigeminal ganglia. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Sensory ganglia (dorsal root ganglia, trigeminal ganglia) | Not available (nTPM not applicable for neuronal tissues) | High expression in nociceptive neurons |
| Lung | Low | Low expression in airway epithelial cells and sensory nerve fibers |
| Colon | Low | Low expression in enteric neurons and epithelial cells |
| Skin | Low | Expression in sensory nerve endings in epidermis and dermis |
| Bladder | Low | Expression in sensory nerves innervating bladder |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | Not available | Endogenous expression; used in neuronal differentiation studies |
| HEK293 (embryonic kidney) | Not available | Commonly used for heterologous expression of TRPA1 in functional assays |
| A549 (lung carcinoma) | Not available | Low endogenous expression; used in airway inflammation studies |
| HaCaT (keratinocyte) | Not available | Expression in keratinocytes; involved in skin barrier and inflammation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asn855Ser (c.2564A>G) | Missense | Rare (found in FEPS1 families) | Gain-of-function: increases channel activity and neuronal excitability |
| p.Glu179Lys (c.535G>A) | Missense | Rare (reported in FEPS1) | Gain-of-function: alters channel gating |
| p.Arg58Cys (c.172C>T) | Missense | Rare (reported in FEPS1) | Gain-of-function: enhances activation by agonists |
| p.Val975Met (c.2923G>A) | Missense | Rare (reported in FEPS1) | Gain-of-function: increases basal activity |
| p.Leu528Pro (c.1583T>C) | Missense | Rare (reported in FEPS1) | Gain-of-function: alters channel kinetics |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TRPA1 are rare and not well characterized. Some variants may reduce channel expression or activity, potentially leading to impaired pain sensation, but no specific disease has been firmly associated with loss-of-function in humans.
Gain of Function (GOF)
Gain-of-function mutations are the primary pathogenic mechanism in familial episodic pain syndrome 1 (FEPS1). These mutations increase channel opening probability, enhance calcium influx, and cause hyperexcitability of sensory neurons, leading to spontaneous pain episodes.
Dominant Negative (DN)
No dominant-negative mutations have been reported for TRPA1. The channel functions as a tetramer, and most pathogenic variants are gain-of-function with dominant inheritance.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pain sensation and nociception
• Neurogenic inflammation
• Thermosensation (cold and heat)
• Chemical irritant detection
• Inflammatory mediator signaling (e.g.
• bradykinin
• prostaglandins)
• Oxidative stress response
• TRP channel signaling
Protein Summary
The TRPA1 protein is a 1,119-amino acid, six-transmembrane domain ion channel that forms tetramers. It contains multiple ankyrin repeats in its N-terminal cytoplasmic domain, which are involved in protein-protein interactions and channel regulation. TRPA1 is activated by electrophilic compounds that covalently modify cysteine residues, as well as by non-electrophilic activators like cold and mechanical stimuli. Upon activation, it mediates calcium and sodium influx, leading to membrane depolarization and neuronal excitation. TRPA1 is a key player in the detection of noxious stimuli and is a major target for analgesic drug development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRPA1 Overexpression HEK293 Stable Cell Line | EDJ-GQ74 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout HEK293 Cell Line | EDJ-KQ1284 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout A-549 Cell Line | EDJ-KQ21981 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout HeLa Cell Line | EDJ-KQ21983 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout HCT 116 Cell Line | EDJ-KQ72001 | Human | 8989 | Details Get a Quote |
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