{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGenome‐wide association studies have implicated XKR4 as one of several loci associated with neuropsychiatric outcomes. In studies evaluating the efficacy of the antipsychotic iloperidone in schizophrenia, variants in the XKR4 gene were identified among a set of candidate markers that may help predict treatment response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In an independent investigation targeting attention deficit/hyperactivity disorder, SNPs within the XKR4 gene—expressed in the cerebellum—were also noted among top candidates, suggesting that genetic variation in this gene might contribute to aspects of disease risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond neuropsychiatric associations, XKR4 has emerged in endocrine studies. A genome‐wide association analysis in Chinese populations identified a novel TSH susceptibility locus within XKR4, with the associated allele correlating with lower serum TSH levels and a modest increase in risk for papillary thyroid carcinoma. This suggests that alterations in or near XKR4 might influence thyroid function and related pathophysiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, XKR4 functions as a phospholipid scramblase involved in the execution of apoptosis. Investigations into its activation revealed that caspase‐mediated cleavage induces dimer formation and, upon interaction with an activating fragment derived from the nuclear protein XRCC4, leads to a structural change that promotes phosphatidylserine exposure on the plasma membrane—a key event in efferocytosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "C Lavedan, L Licamele, S Volpi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2008.56"}], "href": "https://doi.org/10.1038/mp.2008.56"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18521090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18521090"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Simona Volpi, Steven G Potkin, Anil K Malhotra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Applicability of a genetic signature for enhanced iloperidone efficacy in the treatment of schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Psychiatry (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4088/jcp.08m04391"}], "href": "https://doi.org/10.4088/jcp.08m04391"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19573479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19573479"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Francesca Lantieri, Joseph T Glessner, Hakon Hakonarson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of GWAS top hits in ADHD suggests association to two polymorphisms located in genes expressed in the cerebellum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.31110"}], "href": "https://doi.org/10.1002/ajmg.b.31110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20607790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20607790"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ming Zhan, Gang Chen, Chun-Ming Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu250"}], "href": "https://doi.org/10.1093/hmg/ddu250"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24852370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24852370"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Masahiro Maruoka, Panpan Zhang, Hiromi Mori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caspase cleavage releases a nuclear protein fragment that stimulates phospholipid scrambling at the plasma membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2021.02.025"}], "href": "https://doi.org/10.1016/j.molcel.2021.02.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33725486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33725486"}]}]}]}