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In several cases, the genetic variation of a single OR affects the perception of its cognate odor ligand. Musks are widely used for fragrance and are known to demonstrate specific anosmia. It, however, remains to be elucidated whether the OR polymorphism contributes to individual variations in musk odor perception. Previous studies reported that responses of the human musk receptor OR5AN1 to a variety of musks in vitro correlated well with perceptual sensitivity to those odors in humans and that the mouse ortholog, Olfr1440 (MOR215-1), plays a critical role in muscone perception. Here, we took advantage of genetic variation in OR5AN1 to examine how changes in receptor sensitivity are associated with human musk perception. We investigated the functional differences between OR5AN1 variants in an in vitro assay and measured both perceived intensity and detection threshold in human subjects with different OR5AN1 genotypes. Human subjects homozygous for the more sensitive L289F allele had a lower detection threshold for muscone and found macrocyclic musks to be more intense than subjects homozygous for the reference allele. These results demonstrate that the genetic variation in OR5AN1 contributes to perceptual differences for some musks. In addition, we found that the more functional variant of OR5A1, a receptor involved in \u03b2-ionone perception, is associated with the less functional variant of OR5AN1, suggesting that the perceived intensities of macrocyclic musks and \u03b2-ionone are inversely correlated.<\/jats:p>","DOI":"10.1093\/chemse\/bjac037","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T04:36:41Z","timestamp":1673325401000},"source":"Crossref","is-referenced-by-count":12,"title":["Genetic variation in the human olfactory receptor OR5AN1 associates with the perception of musks"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5538-3764","authenticated-orcid":false,"given":"Narumi","family":"Sato-Akuhara","sequence":"first","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-9919","authenticated-orcid":false,"given":"Casey","family":"Trimmer","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center , Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-2214","authenticated-orcid":false,"given":"Andreas","family":"Keller","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Behavior, The Rockefeller University , New York, NY ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7010-2537","authenticated-orcid":false,"given":"Yoshihito","family":"Niimura","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657 ,","place":["Japan"]},{"name":"Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki , 1-1, Gakuen Kibanadai Nishi, Miyazaki, Miyazaki 889-2192 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0877-5428","authenticated-orcid":false,"given":"Mika","family":"Shirasu","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-4598","authenticated-orcid":false,"given":"Joel D","family":"Mainland","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Department of Neuroscience, University of Pennsylvania School of Medicine , Philadelphia, PA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7856-0786","authenticated-orcid":false,"given":"Kazushige","family":"Touhara","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"issue":"7319","key":"2026041420025406500_CIT0001","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing","volume":"467","author":"Abecasis","year":"2010","journal-title":"Nature"},{"issue":"4","key":"2026041420025406500_CIT0002","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/chemse\/2.4.401","article-title":"Specific anosmias to 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