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*608923
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TRACE AMINE-ASSOCIATED RECEPTOR 6; TAAR6
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| Alternative titles; symbols |
| TRACE AMINE RECEPTOR 4; TRAR4 |
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| HGNC Approved Gene Symbol: TAAR6 |
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Cytogenetic location: 6q23.2
Genomic coordinates (GRCh37): 6:132,891,460-132,892,497 (from NCBI)
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Description
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The TAAR6 (TRAR4) gene belongs to the trace amine receptor family. Trace amines are endogenous amine compounds that are chemically similar to classic biogenic amines like dopamine, norepinephrine, serotonin, and histamine. Trace amines were thought to be 'false transmitters' that displace classic biogenic amines from their storage and act on transporters in a fashion similar to the amphetamines, but the identification of brain receptors specific to trace amines indicates that they also have effects of their own (Duan et al., 2004).  |
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Cloning and Expression
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Using RT-PCR, Duan et al. (2004) found that TRAR4 was expressed at low abundance in various human brain tissues as well as in human fetal liver, but not in the cerebellum or placenta. Quantitative RT-PCR revealed that TRAR4 has comparable levels of expression in basal ganglia, frontal cortex, substantia nigra, amygdala, and hippocampus, with the highest expression in hippocampus and the lowest expression in basal ganglia. These results were consistent with a previous expression study that included TRAR4 (Borowsky et al., 2001).
By screening the genomic sequence using a nonredundant set of all vertebrate G protein-coupled receptors as queries, Lindemann et al. (2005) identified TAAR6. The deduced 345-amino acid protein shows several structural features characteristic of the rhodopsin (180380)/beta-adrenergic receptor (see 109630) superfamily, including 7 transmembrane regions, which provide a common ligand-binding pocket, and short N- and C-terminal domains. |
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Gene Structure
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| Lindemann et al. (2005) determined that the coding region of TAAR6 is contained within a single exon. |
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Mapping
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| Duan et al. (2004) showed that the TRAR4 gene is located within a gene cluster spanning 132.8 cM on chromosome 6q23.2 which contains all known TRAR genes, 3 TRAR pseudogenes, MOXD1, and STX7 (603217). |
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Molecular Genetics
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| Duan et al. (2004) genotyped 192 pedigrees with schizophrenia (see 603175), of European or African American ancestry, from samples that previously showed linkage evidence to 6q13-q26. They selected 31 screening SNPs in the gene cluster on 6q23.2 that contains the TRAR4 gene. An association of schizophrenia with 1 SNP within the TRAR4 gene (rs4305745) remained significant after correction for multiple testing. This and/or 2 other polymorphisms in perfect linkage disequilibrium with the first appeared to be the most likely variants underlying the association of the TRAR4 region with schizophrenia. Comparative genomic analyses suggested that these polymorphisms could potentially affect gene expression. Moreover, RT-PCR studies of various human tissues, including brain, confirmed that TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. Duan et al. (2004) concluded that these data provided strong preliminary evidence that TRAR4 is a candidate gene for schizophrenia. |
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| REFERENCES |
| 1. |
Borowsky, B., Adham, N., Jones, K. A., Raddatz, R., Artymyshyn, R., Ogozalek, K. L., Durkin, M. M., Lakhlani, P. P., Bonini, J. A., Pathirana, S., Boyle, N., Pu, X., Kouranova, E., Lichtblau, H., Ochoa, F. Y., Branchek, T. A., Gerald, C.
Trace amines: identification of a family of mammalian G protein-coupled receptors.
Proc. Nat. Acad. Sci. 98: 8966-8971, 2001.
[PubMed: 11459929, images, related citations]
[Full Text]
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| 2. |
Duan, J., Martinez, M., Sanders, A. R., Hou, C., Saitou, N., Kitano, T., Mowry, B. J., Crowe, R. R., Silverman, J. M., Levinson, D. F., Gejman, P. V.
Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia.
Am. J. Hum. Genet. 75: 624-638, 2004.
[PubMed: 15329799, images, related citations]
[Full Text]
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| 3. |
Lindemann, L., Ebeling, M., Kratochwil, N. A., Bunzow, J. R., Grandy, D. K., Hoener, M. C.
Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors.
Genomics 85: 372-385, 2005.
[PubMed: 15718104, related citations]
[Full Text]
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| Contributors: |
Matthew B. Gross - updated : 4/26/2005 |
| Creation Date: |
Victor A. McKusick : 9/15/2004 |
| ▸ Edit History: |
carol : 05/15/2006 |
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mgross : 4/26/2005
tkritzer : 9/17/2004
tkritzer : 9/16/2004 |
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