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Permian alkaline granitoids are widely distributed throughout the Tien Shan Orogen and adjacent region of the southern Central Asian Orogenic Belt. However, their petrogenesis and related tectonic setting remain equivocal. A detailed mineralogical, U-Pb zircon dating, in situ elemental and Sr-Nd-Hf isotopic studies of the uranium-rich Akkulen syenite intrusion in the Northern Tien Shan of Kyrgyzstan were undertaken to better understand its magmatic processes and geodynamic evolution. Four independent oxygen barometers have shown that the oxygen fugacity of the Akkulen syenitic magma evolved from initial low fO2 (NNO +1) during magma ascent and cooling; Apatite geochemical characteristics also indicate that the magma is relatively high F (2.9–5.1 wt.%), with low Cl (0.053–0.13 wt.%) and anhydrous (<4 wt %) contents. According to whole-rock geochemical data, the syenite samples have abnormally high U (38.5–57.1 ppm) and Th (96.2–137 ppm) concentrations, we suggest that high F content and moderate oxygen fugacity are beneficial for uranium enrichment. Zircon grains from a syenite sample yielded a weighted 206Pb/238U age of 283.5 ± 2.6 Ma. The intrusion has an A-type granite affinity with high alkali (Na2O + K2O) contents and Fe/(Fe+Mg) ratios, high LREE/HREE (~5), and low Sr, Ba, and Eu contents. They have negative εNd(t) (−5.2 to −3.6) values with Mesoproterozoic two-stage model ages (T DM2 = 1.35–1.47 Ga), and variable εHf(t) values (−4.6 to +2.4) with Mesoproterozoic two-stage model ages (T DM2 = 1. 2–1.59 Ga), which suggest these rock derivations from the relatively old crustal with minor contribution from juvenile crustal melts. In comparison with regional available dataset, we propose that the alkaline Permian granitoids in Kyrgyz Northern Tien Shan may have been originated from large-scale partial melting of Mesoproterozoic metamorphic basement with minor juvenile crustal material in a post-extensional setting. In contrast, the Early Permian granitoid magmatism in the Tarim Craton may have been caused by the partial melting of Neoproterozoic basement rocks associated with Permian mantle plume activities. [ABSTRACT FROM AUTHOR]