TRPA1

transient receptor potential cation channel subfamily A member 1, the group of Ankyrin repeat domain containing|Transient receptor potential cation channels

Basic information

Region (hg38): 8:72019916-72075584

Previous symbols: [ "ANKTM1" ]

Links

ENSG00000104321 ∙ NCBI:8989 ∙ OMIM:604775 ∙ HGNC:497 ∙ Uniprot:O75762 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial episodic pain syndrome with predominantly upper body involvement (Supportive), mode of inheritance: AD
• familial episodic pain syndrome with predominantly upper body involvement (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Episodic pain syndrome, familial, 1	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	20547126
Individuals have been described as suffering from episodes of severe pain that could, to some extent, be predicted and ameliorated, but it is unclear if genetic diagnosis would be additionally advantageous (in addition to clinical diagnosis)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPA1 gene.

• Inborn genetic diseases (40 variants)
• not provided (29 variants)
• Familial episodic pain syndrome with predominantly upper body involvement (17 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPA1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	4	3	8
missense			43	7	4	54
nonsense			2	2		4
start loss						0
frameshift			5			5
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding					5	5
Total	0	0	51	13	12

Variants in TRPA1

This is a list of pathogenic ClinVar variants found in the TRPA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-72022916-A-G		not specified	Likely benign (Oct 27, 2023)
8-72023100-A-G		not specified	Uncertain significance (Jan 09, 2024)
8-72023839-T-C		not specified	Uncertain significance (Dec 21, 2022)
8-72023867-TTCTTG-T			Uncertain significance (Jul 23, 2020)
8-72023910-T-C		Familial episodic pain syndrome with predominantly upper body involvement • TRPA1-related disorder	Benign (Sep 10, 2021)
8-72023917-G-A		TRPA1-related disorder	Benign (Feb 01, 2024)
8-72026025-G-A		TRPA1-related disorder	Benign/Likely benign (Aug 01, 2022)
8-72026097-G-C		Familial episodic pain syndrome with predominantly upper body involvement	Benign (Sep 10, 2021)
8-72026122-A-C		Familial episodic pain syndrome with predominantly upper body involvement	Benign (Sep 10, 2021)
8-72029895-A-G			Benign (Dec 01, 2023)
8-72029906-T-C		not specified	Uncertain significance (Aug 22, 2023)
8-72029939-C-A		not specified	Uncertain significance (Oct 17, 2023)
8-72029952-G-A		TRPA1-related disorder	Benign/Likely benign (Jul 01, 2022)
8-72029975-G-T		Familial episodic pain syndrome with predominantly upper body involvement	Benign (Sep 10, 2021)
8-72033691-G-T		not specified	Uncertain significance (Jun 16, 2023)
8-72033698-A-G		TRPA1-related disorder	Likely benign (May 22, 2020)
8-72033757-G-A			Likely benign (Nov 01, 2023)
8-72033762-T-C		not specified	Uncertain significance (Aug 01, 2022)
8-72034341-C-T		TRPA1-related disorder	Likely benign (Apr 24, 2019)
8-72034352-C-A		Familial episodic pain syndrome with predominantly upper body involvement	Uncertain significance (Nov 21, 2023)
8-72034369-T-C		Familial episodic pain syndrome with predominantly upper body involvement	Pathogenic (Jun 10, 2010)
8-72036278-C-T		TRPA1-related disorder	Likely benign (Mar 03, 2020)
8-72036323-G-T		not specified	Uncertain significance (Aug 17, 2020)
8-72036324-T-G		not specified	Uncertain significance (May 04, 2023)
8-72036353-C-T		TRPA1-related disorder	Benign (Oct 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPA1	protein_coding	protein_coding	ENST00000262209	27	55701

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.23e-35	0.0000690	125436	1	311	125748	0.00124

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0357	592	594	0.996	0.0000293	7478
Missense in Polyphen		200	208.96	0.9571		2717
Synonymous	-0.718	222	209	1.06	0.0000111	1996
Loss of Function	0.540	55	59.5	0.925	0.00000304	731

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00152	0.00150
Ashkenazi Jewish	0.000597	0.000397
East Asian	0.000986	0.000979
Finnish	0.000280	0.000277
European (Non-Finnish)	0.00139	0.00137
Middle Eastern	0.000986	0.000979
South Asian	0.00296	0.00291
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity). {ECO:0000250|UniProtKB:Q8BLA8, ECO:0000269|PubMed:20547126, ECO:0000269|PubMed:25389312, ECO:0000269|PubMed:25855297}.
• Disease: DISEASE: Episodic pain syndrome, familial, 1 (FEPS1) [MIM:615040]: An autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress. The period of intense pain is accompanied by breathing difficulties, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall. Affected individuals do not manifest altered pain sensitivity outside the episodes. {ECO:0000269|PubMed:20547126}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Intolerance Scores

• loftool: 0.662
• rvis_EVS: 0.79
• rvis_percentile_EVS: 87.29

Haploinsufficiency Scores

• pHI: 0.137
• hipred: N
• hipred_score: 0.275

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trpa1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; taste/olfaction phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: trpa1b
• Affected structure: chemosensory behavior
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: ion transport;cell surface receptor signaling pathway;response to cold;response to organic substance;response to organic cyclic compound;sensory perception of pain;response to hydrogen peroxide;response to pain;thermoception;detection of mechanical stimulus involved in sensory perception of pain;detection of chemical stimulus involved in sensory perception of pain;release of sequestered calcium ion into cytosol;protein homotetramerization;calcium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;stereocilium bundle
• Molecular function: calcium channel activity;channel activity;calcium-release channel activity;identical protein binding;temperature-gated cation channel activity