{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have established that FADS3 is a bona fide lipid desaturase that plays a critical role in sphingolipid de novo synthesis. Specifically, FADS3 catalyzes the introduction of a Δ14 double bond in long‐chain base (LCB) backbones to form dienic LCBs (e.g. sphingadienine) and converts the atypical, cytotoxic 1‑deoxysphinganine into the less toxic 1‑deoxysphingosine. In addition, multiple studies have demonstrated that FADS3 exists as several protein isoforms and alternative transcripts with tissue‐specific expression patterns that correlate with distinct fatty acid profiles, suggesting a regulatory role in the synthesis of highly unsaturated fatty acids (HUFA) in tissues such as liver, brain, and even the decidualized uterus. Moreover, knockout mouse models and hormonal studies indicate that FADS3 function contributes to liver-mediated DHA synthesis critical for brain accretion, and its expression is upregulated by estrogen and progesterone during decidualization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, work on the C12orf4 gene has revealed a distinct cellular function for its encoded protein, which has been implicated in intracellular signaling events. Initially identified through an intrabody‐based screen in mast cells, the C12orf4 protein appears to be a cytoplasmic factor that participates in early signaling following FcεRI-mediated cell activation. Clinically, mutations in C12orf4 are associated with autosomal recessive intellectual disability, with studies reporting both missense and frameshift variants in affected individuals, thereby establishing C12orf4 as a causative gene for intellectual disability in different populations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Frédérique Pédrono, Hélène Blanchard, Maela Kloareg, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Fads3 modulates docosahexaenoic acid in liver and brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostaglandins Leukot Essent Fatty Acids (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.plefa.2017.07.001"}], "href": "https://doi.org/10.1016/j.plefa.2017.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28838557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28838557"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shuai Lin, Yu-Yuan Zhu, Wei Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decidual expression and regulation of fatty acid desaturase 3 during mouse decidualization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reproduction (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/REP-18-0145"}], "href": "https://doi.org/10.1530/REP-18-0145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30400035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30400035"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gergely Karsai, Museer Lone, Zoltán Kutalik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FADS3 is a Δ14Z sphingoid base desaturase that contributes to gender differences in the human plasma sphingolipidome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.AC119.011883"}], "href": "https://doi.org/10.1074/jbc.AC119.011883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31862735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31862735"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elsa Mazuc, Laurence Guglielmi, Nicole Bec, et al. 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