{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAP3D1 encodes the δ‐subunit of the adaptor protein complex 3 (AP‑3), which plays a pivotal role in intracellular trafficking by mediating the sorting of membrane proteins into transport vesicles. Several studies have shown that the AP‑3 complex directs essential cargo—including retroviral proteins such as the HIV‑1 Gag polyprotein—to specific endosomal compartments required for productive viral assembly, as well as orchestrates the delivery of specialized cargos in melanocytes. These functions underscore its importance in regulating membrane dynamics and organelle biogenesis."}, {"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": "\nBeyond its basic cellular functions, AP3D1 has emerged as a gene of clinical significance. Genome‐wide association studies have identified AP3D1 as part of a susceptibility locus for myocardial infarction, and functional analyses in lung tissue have revealed its involvement in the secretion of transforming growth factor‐β2 via an AP‑3–dependent pathway, implicating it in chronic obstructive pulmonary disease pathogenesis. Moreover, deleterious variants in AP3D1 cause Hermansky–Pudlak Syndrome type 10—a severe multisystem disorder characterized by albinism, immunodeficiency, and neurodevelopmental delay—and missense mutations have been linked to hearing loss, highlighting a crucial role in tissue‐specific functions. Notably, while one study explored its involvement in neuropsychiatric conditions such as schizophrenia, no strong association was found."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings illustrate that AP3D1 is a key component of the AP‑3 machinery, essential for targeting proteins to lysosome‐related organelles and for the proper trafficking of specific cargo molecules in both normal physiology and disease. The diverse functions of AP3D1—from mediating viral assembly and organelle biogenesis to influencing disease outcomes in cardiovascular, pulmonary, and pigmentary as well as auditory systems—highlight its potential as a therapeutic target in conditions where intracellular transport is disrupted."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xinhong Dong, Hua Li, Aaron Derdowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AP-3 directs the intracellular trafficking of HIV-1 Gag and plays a key role in particle assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2004.12.023"}], "href": "https://doi.org/10.1016/j.cell.2004.12.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15766529"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15766529"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexander C Theos, Danièle Tenza, José A Martina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e05-07-0626"}], "href": "https://doi.org/10.1091/mbc.e05-07-0626"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16162817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16162817"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Eduardo Garcia, Damjan S Nikolic, Vincent Piguet "}, {"type": "b", "children": [{"type": "t", "text": "HIV-1 replication in dendritic cells occurs through a tetraspanin-containing compartment enriched in AP-3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2007.00678.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2007.00678.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18034776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18034776"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sampson K Kyere, Peter Y Mercredi, Xinhong Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The HIV-1 matrix protein does not interact directly with the protein interactive domain of AP-3δ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virus Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.virusres.2012.06.007"}], "href": "https://doi.org/10.1016/j.virusres.2012.06.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22705971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22705971"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shanna L Bowman, Linh Le, Yueyao Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A BLOC-1-AP-3 super-complex sorts a cis-SNARE complex into endosome-derived tubular transport carriers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.202005173"}], "href": "https://doi.org/10.1083/jcb.202005173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33886957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33886957"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ryota Hashimoto, Kazutaka Ohi, Takeya Okada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association analysis between schizophrenia and the AP-3 complex genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neures.2009.05.008"}], "href": "https://doi.org/10.1016/j.neures.2009.05.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19481122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19481122"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Megumi Hirokawa, Hiroyuki Morita, Tomoyuki Tajima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2014.110"}], "href": "https://doi.org/10.1038/ejhg.2014.110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24916648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24916648"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mohammed Mohammed, Nadia Al-Hashmi, Samiya Al-Rashdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic mutations in AP3D1 cause Hermansky-Pudlak syndrome type 10 associated with immunodeficiency and seizure disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2018.11.017"}], "href": "https://doi.org/10.1016/j.ejmg.2018.11.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30472485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30472485"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lu Gong, Samuel Bates, Jian Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Connecting COPD GWAS Genes: FAM13A Controls TGFβ2 Secretion by Modulating AP-3 Transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2021-0016OC"}], "href": "https://doi.org/10.1165/rcmb.2021-0016OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34166600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34166600"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Alexandra Frohne, Martin Koenighofer, Hakan Cetin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous AP3D1 missense variant in patients with sensorineural hearing loss as the leading manifestation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-022-02506-0"}], "href": "https://doi.org/10.1007/s00439-022-02506-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36445457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36445457"}]}]}]}