{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTSPOAP1 encodes a presynaptic active‐zone protein that belongs to the RIM‐binding protein family. These proteins possess a modular architecture characterized by multiple SH3 domains and fibronectin III repeats that mediate protein–protein interactions essential for tethering voltage‐gated Ca²⁺ channels to the synaptic vesicle release machinery. Such a conserved domain structure supports their role as molecular adaptors that ensure efficient and tightly regulated neurotransmitter release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its coding function, a long noncoding RNA—TSPOAP1‐AS1—originating from this locus has been identified as a regulator of host antiviral responses. Induced in a dose‐ and time‐dependent manner by influenza A virus infection (and by a synthetic double‐stranded RNA analog), TSPOAP1‐AS1 shuttles between the nucleus and cytoplasm and modulates innate immunity by dampening interferon‐β transcription, interferon-sensitive response element (ISRE) activation, and downstream interferon-stimulated gene expression, thereby promoting viral replication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, mutations in TSPOAP1 have been directly linked to dystonia. Homozygous loss-of-function variants, including frameshift and nonsense mutations, lead to juvenile-onset generalized dystonia accompanied by intellectual disability and cerebellar atrophy, while a specific missense mutation (p.Gly1808Ser) is associated with adult-onset focal dystonia. Functional studies in mice revealed that ablation of TSPOAP1 (which encodes RIM-binding protein 1) results in motor abnormalities, reduced Purkinje cell dendritic arborization, and diminished cerebellar synapses, whereas the missense variant produces larger, spike-evoked Ca²⁺ transients and enhanced neurotransmission. Together, these findings underscore that precise control of presynaptic Ca²⁺-dependent exocytosis by TSPOAP1 is critical for balanced neurotransmission and motor control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tobias Mittelstaedt, Susanne Schoch "}, {"type": "b", "children": [{"type": "t", "text": "Structure and evolution of RIM-BP genes: identification of a novel family member."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2007.08.004"}], "href": "https://doi.org/10.1016/j.gene.2007.08.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17855024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17855024"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qi Wang, Daining Zhang, Wenjing Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA TSPOAP1 antisense RNA 1 negatively modulates type I IFN signaling to facilitate influenza A virus replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Virol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jmv.25483"}], "href": "https://doi.org/10.1002/jmv.25483"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30968963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30968963"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Niccolò E Mencacci, Marisa M Brockmann, Jinye Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI140625"}], "href": "https://doi.org/10.1172/JCI140625"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33539324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33539324"}]}]}]}