PER3（Period Circadian Regulator 3）是生物钟调控基因家族Period（Per）的重要成员之一，属于核心生物钟基因家族。该家族还包括PER1和PER2，它们共同参与调控哺乳动物的昼夜节律（约24小时的生理和行为周期）。PER3基因编码的蛋白质与CRY（隐花色素）蛋白形成复合物，抑制CLOCK/BMAL1转录因子的活性，从而形成负反馈环路维持昼夜节律的稳定性。PER3主要在视交叉上核（SCN，大脑的主要生物钟中枢）和外周组织中表达，其表达水平呈现明显的昼夜波动。PER3蛋白的特点是含有PAS结构域（介导蛋白质相互作用）和核定位信号，可与其他生物钟蛋白协同进入细胞核发挥作用。PER3基因突变可能导致睡眠相位前移或延迟，例如rs57875989多态性与“早睡早起”表型相关，而某些罕见突变可能引发家族性睡眠相位提前综合征（FASPS）。研究发现PER3表达降低与失眠、抑郁症和双相情感障碍风险增加相关，其昼夜节律紊乱还可能影响代谢功能（如葡萄糖代谢异常）。当过表达PER3时可能增强生物钟的稳定性但可能降低对光重置的敏感性；而敲低表达则导致昼夜节律振幅减弱、睡眠结构紊乱（REM睡眠减少）以及认知功能下降。值得注意的是，PER3长度多态性（如5重复等位基因）与应对睡眠剥夺的能力差异显著相关。该基因还与肿瘤发生存在关联，在某些癌症中显示异常甲基化模式。PER基因家族的共性在于都含有PAS结构域、参与负反馈调节环路、蛋白质稳定性受磷酸化调控（如CK1ε/δ介导的降解），且均表现出昼夜振荡表达模式。不同PER家族成员可能存在功能冗余，但组织特异性表达和调控差异使其在精细调节生物钟方面各具特色。

该基??因是时期基因家族的成员，并在视交叉上核，在哺乳动物脑的主要昼夜起搏器昼夜图案表示。基因的活动能力，代谢和行为的昼夜节律的这个家族编码的组件。该基因是由时钟/ ARNTL异上调但随后压制这种上调使用PER / CRY异与时钟/ ARNTL互动反馈环路。在这种基因多态性已与睡眠障碍。已发现该基因编码不同亚型的多个抄本变形。 [由RefSeq的，2014年1月提供]

PER3 (Period Circadian Regulator 3) is a core component of the Period (Per) gene family, which, alongside PER1 and PER2, plays a pivotal role in orchestrating the mammalian circadian rhythm, the approximately 24-hour cycle governing physiological and behavioral processes. The PER3 protein, characterized by the presence of PAS domains that facilitate protein-protein interactions and a nuclear localization signal, forms a critical inhibitory complex with CRY (Cryptochrome) proteins. This complex acts to suppress the transcriptional activity of the CLOCK/BMAL1 heterodimer, thereby establishing a negative feedback loop that maintains the stability and precision of the circadian oscillation. Expression of PER3 is prominent in the suprachiasmatic nucleus (SCN), the master pacemaker of the brain, as well as in peripheral tissues, where its levels exhibit robust circadian oscillations. The stability and function of PER3, like other PER family members, are tightly regulated by phosphorylation events, particularly those mediated by casein kinase 1 epsilon and delta (CK1ε/δ), which target the protein for degradation. Genetic variations in PER3 have significant clinical and physiological implications; for instance, the rs57875989 polymorphism is associated with a "morningness" phenotype, while specific rare mutations can lead to Familial Advanced Sleep Phase Syndrome (FASPS). Furthermore, altered PER3 expression is linked to an increased risk of sleep disorders, depression, and bipolar disorder, and circadian disruptions involving PER3 may contribute to metabolic abnormalities such as impaired glucose metabolism. Experimental manipulations highlight the gene's nuanced role: overexpression can enhance circadian stability but potentially reduce sensitivity to light-induced phase resetting, whereas knockdown leads to attenuated circadian amplitude, disrupted sleep architecture characterized by reduced REM sleep, and cognitive decline. Notably, PER3 length polymorphisms, such as the 5-repeat allele, are strongly correlated with individual differences in resilience to sleep deprivation. Beyond its primary role in timekeeping, PER3 is implicated in tumorigenesis, with aberrant methylation patterns observed in certain cancers, underscoring the broader biological significance of the PER family in maintaining homeostasis through shared structural motifs and regulatory mechanisms, despite functional redundancies and tissue-specific expression differences.

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