{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have implicated the olfactory receptor OR2W3 in diverse non‐olfactory functions. In one investigation, a novel heterozygous missense mutation (p.R142W) in OR2W3 was reported to co‐segregate with autosomal dominant retinitis pigmentosa (RP) over four generations, suggesting an ocular role for the receptor. However, subsequent data demonstrated that this variant is found at appreciable frequency in the general population, arguing against a pathogenic role for OR2W3 in RP."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its putative involvement in retinal disease, functional studies in airway smooth muscle (ASM) have uncovered a chemosensory signaling mechanism whereby stimulation of OR2W3 by the monoterpene nerol triggers an increase in intracellular Ca²⁺ via store-operated calcium entry. This Ca²⁺ mobilization, together with the activation of Ca²⁺-activated chloride channels, ultimately leads to plasma membrane depolarization and ASM relaxation, suggesting that OR2W3 may serve as a novel target for modulating airway contractility in obstructive lung diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, genetic association studies have explored the potential role of OR2W3 in male reproductive health. Investigations into non-obstructive azoospermia and male infertility have included screening for single nucleotide polymorphisms within OR2W3, implicating the gene as a candidate in the regulation of spermatogenesis. Although further studies are needed to clarify its precise role, these findings open novel avenues for understanding the genetic underpinnings of male infertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiangyu Ma, Liping Guan, Wei Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing identifies OR2W3 mutation as a cause of autosomal dominant retinitis pigmentosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep09236"}], "href": "https://doi.org/10.1038/srep09236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25783483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25783483"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dror Sharon, Adva Kimchi, Carlo Rivolta "}, {"type": "b", "children": [{"type": "t", "text": "OR2W3 sequence variants are unlikely to cause inherited retinal diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmic Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/13816810.2015.1081252"}], "href": "https://doi.org/10.3109/13816810.2015.1081252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26891008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26891008"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jessie Huang, Hong Lam, Cynthia Koziol-White, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2003111117"}], "href": "https://doi.org/10.1073/pnas.2003111117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33097666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33097666"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yan Zhang, Xiao-Jin He, Bing Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of single nucleotide polymorphisms in the USF1, GTF2A1L and OR2W3 genes with non-obstructive azoospermia in the Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-014-0369-y"}], "href": "https://doi.org/10.1007/s10815-014-0369-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25374392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25374392"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Makoto Chihara, Kosuke Yoshihara, Tatsuya Ishiguro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Susceptibility to male infertility: replication study in Japanese men looking for an association with four GWAS-derived loci identified in European men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-015-0468-4"}], "href": "https://doi.org/10.1007/s10815-015-0468-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25847845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25847845"}]}]}]}