a missense mutation of trpa1 was found to be the cause of a hereditary episodic pain syndrome. a family from colombia suffers from "debilitating upper-body pain starting in infancy" that is "usually triggered by fasting or fatigue (illness, cold temperature, and physical exertion being contributory factors)". a gain-of-function mutation in the fourth transmembrane domain causes the channel to be overly sensitive to pharmacological activation.