Pain syndromes

Gene: TRPA1

Green List (high evidence)

Comments from Dave Bennett: Just a word of caution on publication (PMID:28436534). This is interesting but there is no functional analysis of the p.Arg919* which would be really important to see how a heterozygous premature stop codon can cause GAIN of function in the channel- caution is therefore advised in interpretation. (add as comment)

Created: 19 Sep 2017, 9:53 a.m.

The TRPA1 gene encodes for cation channel expressed in primary afferent nociceptors; mutations described in two families.

Created: 27 Jun 2017, 12:36 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Episodic pain syndrome, familial 615040; Familial episodic pain syndrome type I

Publications

• 20547126
• 28436534

I don't know

Comment on list classification: changed from amber to green due to review by Arianna Tucci

Created: 9 Jul 2017, 6:30 p.m.

Comment on list classification: To be reviewed by clinical team for inclusion as a Green gene, refer to new publication PMID:28436534 (2017)

Created: 9 Jul 2017, 4:49 p.m.

Comment on publications: added 28436534 from Arianna Tucci

Created: 9 Jul 2017, 4:48 p.m.

1 large 4 generation family (2010) with one single point mutation. Add tag Treatable. PMID: 28314413. Autosomal dominant mutation was found in a single Colombian family, with carriers experiencing significant pain in various regions of the body in response to changes in environmental conditions. A single-point mutation, N855S, in the S4 loop of TRPA1 causes a shift in gating prop- erties, with a dramatic increase in inward currents and activation at normal resting potentials. Specific TRPA1 antagonists inhibit the abnormal response of the mutant TRPA1 channel in vitro, providing confidence that TRPA1 inhibition will alleviate painful symptoms in sufferers of FEP. Additionally, a mutational variant at position 179 of the TRPA1 ankyrin repeat 4 (E179K) appears to be crucial for the generation of paradoxical heat sensation (PHS) in neuropathic pain patients PMID: 21468319.

Created: 9 Jul 2017, 4:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Episodic pain syndrome, familial; 615040

Publications

• 20547126
• 16564016
• 21468319
• 28314413
• 24778270
• 24564660
• 20718100