Discovery of a null mutation in a human trace amine receptor gene.

G-protein-coupled receptors (GPCRs) are important mediators of signal transduction, and mutations in GPCR-encoding genes can lead to disease states. Here we describe a null mutation in an orphan GPCR-encoding gene that is predicted to inactivate completely the encoded receptor. The TA(3) receptor is a putative member of the recently described mammalian trace amine receptor family, and it is expressed in the pituitary gland and skeletal muscle. We tested for the presence of the mutant form of TA(3) (named TA(3)-TR) in a normal population, as well as in two disease groups (ADHD and bipolar affective disorder). We found TA(3)-TR to be commonly expressed in all groups, with approximately 20% allele frequency. We did not find any statistically significant correlation between either disease and the presence of TA(3)-TR.