Affinage

PER3

Period circadian protein homolog 3 · UniProt P56645

Length
1201 aa
Mass
131.9 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PER3 is a circadian clock-associated protein whose biological output is most clearly defined in sleep homeostasis, where it acts through mechanisms distinct from core circadian timekeeping: the human PER3 VNTR polymorphism and Per3 deficiency alter slow-wave sleep, EEG delta/theta power, and homeostatic recovery from sleep deprivation while leaving melatonin, cortisol, and circadian period unaffected, with humanized knock-in mice showing selective changes in sleep-homeostasis transcripts (Homer1, Ptgs2, Kcna2) rather than clock genes (PMID:24577121, PMID:17346965, PMID:21957163). As a clock output factor, PER3 together with BMAL1 directly binds and regulates the Klf15 promoter to restrain adipogenesis, and Per3 loss promotes fat accumulation in vivo (PMID:29186676). PER3 transcription is itself embedded in clock circuitry, induced by ARNTL/NPAS2 dimers and antagonized by DEC2 (PMID:30210560), and enhanced by TFEB acting on the CLOCK/BMAL1 complex in a glucose-dependent manner (PMID:27373683). Beyond timekeeping, PER3 functions in the DNA-damage checkpoint by physically interacting with ATM and CHK2 and is required for CHK2 activation after damage (PMID:21070773), and acts as a tumor suppressor across multiple cancers by binding HIF-1α through its PAS1 domain to promote its ubiquitination and degradation, thereby blocking EMT and metastasis (PMID:39733745), and by suppressing cancer stem-cell self-renewal via inhibition of Notch and WNT/β-catenin signaling (PMID:27983919, PMID:33816508). PER3 expression is constrained by direct miRNA targeting (miR-103, miR-181a, the circMETTL3/miR-107 axis) and by transcriptional regulators including GLYR1, linking its dosage to adipogenic and tumor-suppressive outcomes (PMID:24393525, PMID:30670712, PMID:35710754, PMID:38642856). PER3 also contributes to cortical neuronal migration and morphogenesis during development (PMID:30971765).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2007 High

    Established that PER3 influences sleep homeostasis independently of circadian timing, resolving whether a clock gene could have a dedicated sleep-regulatory role.

    Evidence Genotype-stratified prospective human study with polysomnography, EEG, cognitive testing, and melatonin/cortisol/mRNA assays comparing PER3 VNTR alleles

    PMID:17346965

    Open questions at the time
    • Does not identify the molecular effector linking the VNTR to slow-wave activity
    • Correlative human genotype association without mechanism
  2. 2010 Medium

    Defined a non-circadian role for PER3 in the DNA-damage response by placing it physically and functionally within the ATM-CHK2 checkpoint.

    Evidence Co-immunoprecipitation with ATM and CHK2, siRNA knockdown, and overexpression with proliferation/apoptosis readouts in human cells

    PMID:21070773

    Open questions at the time
    • No structural basis for the ATM/CHK2 interaction
    • Whether PER3 acts as scaffold, substrate, or activator is unresolved
  3. 2010 Medium

    Showed that natural PER3 promoter variation functionally tunes its expression, linking sequence polymorphism to transcriptional output.

    Evidence Luciferase reporter assays with allele combinations and deletion mapping of enhancer regions

    PMID:20469812

    Open questions at the time
    • Trans-acting factors binding the mapped enhancers not identified
    • Reporter assays not validated at endogenous locus
  4. 2011 High

    Confirmed in a genetic model that PER3 shapes sleep-wake timing and homeostatic recovery, corroborating human findings in mouse.

    Evidence Per3 knockout mice with wheel-running and EEG phenotyping before and after 6-hour sleep deprivation

    PMID:21957163

    Open questions at the time
    • Molecular pathway driving altered delta activity not defined
    • Brain region responsible not localized
  5. 2011 Medium

    Implicated PER3 dosage in chemotherapy-induced apoptosis, opening its role in cancer cell survival.

    Evidence siRNA knockdown in gingival cancer cells with apoptosis assays and Western blot after cisplatin

    PMID:21459569

    Open questions at the time
    • Mechanism linking PER3 to apoptotic machinery not defined
    • Single cell line
  6. 2012 Medium

    Identified a cis-acting promoter variant controlling Per3 abundance through Nrf2 binding, connecting PER3 regulation to stress and alcohol responses.

    Evidence eQTL mapping in BXD mouse strains, allele-specific protein-binding assays, ethanol and restraint stress protocols

    PMID:22832735

    Open questions at the time
    • Direct Nrf2 occupancy at endogenous promoter not shown
    • Functional consequence of altered hippocampal Per3 unclear
  7. 2014 High

    Demonstrated using a humanized model that the PER3 VNTR selectively alters sleep-homeostasis gene expression without perturbing clock genes, mechanistically separating PER3's sleep role from timekeeping.

    Evidence Humanized VNTR knock-in mice, EEG recording, sleep deprivation, microarray of hypothalamus and cortex

    PMID:24577121

    Open questions at the time
    • How the VNTR alters Homer1/Ptgs2/Kcna2 expression is unknown
    • Causal effector among differentially expressed genes not established
  8. 2014 Medium

    Showed PER3 acts as a tumor suppressor in colorectal cancer and is directly repressed by miR-103, establishing post-transcriptional control of its function.

    Evidence Luciferase reporter of miR-103 targeting PER3 3'UTR, miR-103 overexpression, apoptosis assays

    PMID:24393525

    Open questions at the time
    • Downstream apoptotic mediators of PER3 not identified
    • Single cancer context
  9. 2014 Medium

    Found PER3 contributes to acute behavioral suppression by light during photoperiod adaptation, distinguishing a light-response function.

    Evidence Per3 knockout mice with running-wheel activity under varying photoperiods

    PMID:24982860

    Open questions at the time
    • Molecular link between PER3 and light masking unknown
    • Neural circuit not defined
  10. 2016 Medium

    Placed PER3 transcription under control of TFEB acting on CLOCK/BMAL1, revealing a glucose-responsive and PER3-specific regulatory input.

    Evidence Co-IP of TFEB with CLOCK/BMAL1, TFEB loss-of-function in liver, luciferase reporters with glucose treatment

    PMID:27373683

    Open questions at the time
    • Why TFEB selectively regulates PER3 over other PER/CRY genes unexplained
    • Physiological output of glucose-TFEB-PER3 axis not measured
  11. 2016 Medium

    Defined PER3's suppression of cancer stem-cell self-renewal through Notch and β-catenin pathways.

    Evidence Overexpression and knockdown in colorectal cancer stem-like cells with colony/self-renewal assays and Western blot for Notch/β-catenin components

    PMID:27983919

    Open questions at the time
    • Whether PER3 acts directly on Notch/WNT components or indirectly is unresolved
    • No in vivo tumor data
  12. 2017 High

    Established PER3/BMAL1 as direct transcriptional regulators of Klf15 that restrain adipogenesis, defining a concrete clock-output mechanism.

    Evidence Per3 knockout mice, ChIP showing PER3/BMAL1 binding to the Klf15 promoter, in vivo adipogenesis assays

    PMID:29186676

    Open questions at the time
    • How PER3 cooperates with BMAL1 mechanistically at the promoter is undefined
    • Tissue specificity of the PER3-Klf15 axis not mapped
  13. 2017 Medium

    Linked PER3 deficiency to mood-relevant behavior under light stress, broadening its physiological reach.

    Evidence Per3 knockout mice with sucrose preference test, dim-light-at-night protocol, imipramine rescue

    PMID:28071711

    Open questions at the time
    • Molecular pathway connecting PER3 to anhedonia not identified
    • Relationship to circadian phenotypes unclear
  14. 2017 Medium

    Quantified differential PER3 induction by ARNTL2/NPAS2 versus ARNTL/NPAS2 dimers and antagonism by DEC2, refining the transcriptional inputs to PER3.

    Evidence Transfection of clock factors in HEK293 cells with reporter assays and RT-qPCR

    PMID:30210560

    Open questions at the time
    • Endogenous relevance of ARNTL2/NPAS2 to PER3 not tested
    • DEC2 mechanism of blockade not defined
  15. 2019 High

    Revealed a developmental role for PER3 in cortical neuron migration and morphogenesis, beyond its clock and cancer functions.

    Evidence In utero electroporation knockdown with RNAi-resistant rescue, in situ hybridization, imaging of migration and dendrite/axon morphology

    PMID:30971765

    Open questions at the time
    • Molecular effectors of PER3 in migrating neurons unknown
    • Whether this role depends on clock partners untested
  16. 2019 Medium

    Connected PER3 to adipogenesis through direct miR-181a targeting, reinforcing post-transcriptional control of its metabolic function.

    Evidence Luciferase reporter of direct targeting, miR-181a gain- and loss-of-function, adipogenesis assays in stromal cells

    PMID:30670712

    Open questions at the time
    • Whether miR-181a-PER3 converges on the Klf15 pathway not tested
    • In vivo relevance not established
  17. 2022 Medium

    Positioned PER3 as the downstream effector of a RUNX3/circMETTL3/miR-107 tumor-suppressive axis in colorectal cancer.

    Evidence Biotin pulldown, RIP, dual luciferase, ChIP/EMSA for RUNX3/METTL3 promoter, and xenograft model

    PMID:35710754

    Open questions at the time
    • Mechanism of PER3 tumor suppression downstream of this axis not detailed
    • Single cancer type
  18. 2024 Medium

    Defined a direct molecular mechanism for PER3 tumor suppression: PAS1-domain binding to HIF-1α driving its ubiquitination and degradation to block metastasis.

    Evidence Co-IP with domain mapping, ubiquitination assay, bisulfite pyrosequencing of PER3 promoter methylation, and xenograft with decitabine/LW6

    PMID:39733745

    Open questions at the time
    • Whether PER3 recruits an E3 ligase or acts as adaptor is unresolved
    • Single cancer model
  19. 2024 Medium

    Identified GLYR1 as a direct transcriptional activator of PER3 mediating its tumor-suppressive effect in myeloma.

    Evidence Luciferase and ChIP for GLYR1 binding to PER3 promoter, PER3 knockdown/overexpression epistasis, viability/migration assays

    PMID:38642856

    Open questions at the time
    • Downstream PER3 effectors in myeloma not defined
    • GLYR1-PER3 axis not validated in vivo
  20. 2023 Medium

    Linked a coding PER3 variant to pigmentary disease by showing it promotes melanin synthesis and melanocyte proliferation.

    Evidence Whole-exome and Sanger sequencing of a DUH family, in vitro melanin assays, and zebrafish melanocyte proliferation phenotyping

    PMID:36790533

    Open questions at the time
    • Mechanism by which p.P173S alters melanin synthesis unknown
    • Independence from circadian function not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PER3's molecular activities — checkpoint scaffolding, HIF-1α degradation, and transcriptional co-regulation — mechanistically connect to its defining sleep-homeostatic phenotype remains unresolved.
  • No structural model of PER3 domains in any complex
  • The effector linking the VNTR to slow-wave sleep is unidentified
  • Whether PER3's tumor-suppressive and sleep roles share a mechanism is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-9909396 Circadian clock 4 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 1
Partners
ATMBMAL1CHK2HIF-1ΑTFEB

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 PER3 physically interacts with ATM and CHK2; depletion of PER3 by siRNA almost completely abolishes CHK2 activation after DNA damage; PER3 overexpression induces CHK2 activation in an ATM-dependent manner and leads to inhibition of cell proliferation and apoptotic cell death. siRNA knockdown, co-immunoprecipitation (physical interaction with ATM and CHK2), overexpression assays in human cells FEBS letters Medium 21070773
2017 PER3 and BMAL1 directly regulate Klf15 expression in adipocyte precursor cells (APCs); deletion of Per3 promotes adipogenesis in vivo via this clock output pathway. Per3 knockout mice, chromatin immunoprecipitation (ChIP) demonstrating direct binding of PER3/BMAL1 to Klf15 promoter, in vivo adipogenesis assays Cell reports High 29186676
2014 Introducing the human PER3 VNTR polymorphism (4 or 5 repeats) into mice alters sleep homeostatic responses (EEG theta power during wakefulness and delta power during sleep after sleep deprivation) without affecting circadian parameters; differentially expressed transcripts include sleep homeostasis-related genes Homer1, Ptgs2, and Kcna2 but not circadian clock genes. Humanized knock-in mice, EEG sleep recording, sleep deprivation protocol, microarray gene expression analysis of hypothalamus and cortex FASEB journal High 24577121
2007 The PER3 VNTR polymorphism (5-repeat homozygotes vs. 4-repeat) affects sleep homeostasis markers including slow-wave sleep, EEG slow-wave activity in NREM, and theta/alpha activity during wakefulness and REM, and increases cognitive performance decrement after sleep loss, without affecting circadian rhythms of melatonin, cortisol, or peripheral PER3 mRNA expression. Prospective controlled study with PER3 genotype-stratified participants, polysomnography, EEG, cognitive performance testing, melatonin/cortisol assays, PER3 mRNA expression in peripheral blood Current biology : CB High 17346965
2011 Per3-deficient mice show altered temporal distribution of wheel-running activity and vigilance states; REM and NREM sleep are reduced in the middle of the dark phase; EEG delta activity is enhanced at end of dark phase; after sleep deprivation, Per3−/− mice spend less time in wakefulness and more time in NREM sleep, and REM sleep accumulates more slowly during recovery—confirming a role for PER3 in sleep-wake timing and sleep homeostasis. Per3 knockout mice, wheel-running activity recording, polysomnography/EEG sleep recording before and after 6-hour sleep deprivation American journal of physiology. Regulatory, integrative and comparative physiology High 21957163
2011 PER3 knockdown in human gingival cancer CA9-22 cells has an inhibitory effect on CDDP-induced apoptosis (pro-apoptotic role), while PER1 knockdown enhances apoptosis; PER3 expression is downregulated by cisplatin treatment in CA9-22 cells. siRNA-mediated knockdown of PER3, apoptosis assays, Western blot for Bim and other apoptosis markers, immunohistochemistry European journal of cancer Medium 21459569
2016 Overexpression of PER3 in colorectal cancer stem-like cells reduces colony formation, self-renewal efficiency, and chemoresistance via inhibition of Notch and β-catenin signaling pathways; knockdown of PER3 enhances self-renewal. PER3 overexpression decreased Notch1, Jagged1, β-catenin, c-Myc, and LGR5. PER3 overexpression and knockdown in colorectal cancer stem-like cells (HCT-116 sphere-forming), soft agar colony formation, Western blot, qRT-PCR, Notch/β-catenin inhibition experiments Oncology research Medium 27983919
2021 Low levels of PER3 stimulate BMAL1 expression, leading to phosphorylation of β-catenin and activation of the WNT/β-catenin pathway, thereby promoting stemness of prostate cancer stem cells; PER3 overexpression suppresses sphere- and colony-forming abilities and tumorigenicity. PER3 overexpression and knockdown in prostate cancer stem cells, sphere/colony assays, tumorigenicity in immunodeficient mice, Western blot for WNT/β-catenin pathway components Frontiers in cell and developmental biology Medium 33816508
2016 TFEB physically interacts with the CLOCK/BMAL1 complex through its N-terminal region and enhances BMAL1/CLOCK-mediated transcription of PER3 specifically; loss of TFEB function disrupts PER3 expression without affecting PER1, PER2, CRY1, or CRY2; the TFEB/CLOCK/BMAL1 complex is regulated by glucose. Co-immunoprecipitation (TFEB-CLOCK/BMAL1 interaction), TFEB loss-of-function in liver, luciferase reporter assays, glucose treatment The international journal of biochemistry & cell biology Medium 27373683
2017 The ARNTL2/NPAS2 dimer is a weaker inducer of PER3 and DBP expression than the ARNTL/NPAS2 dimer; DEC2 blocks the effect of the ARNTL2/NPAS2 dimer on PER3 expression. Transfection of cloned ARNTL, ARNTL2, NPAS2, DEC1, DEC2 in HEK293 cells, reporter gene assays, RT-qPCR Journal of circadian rhythms Medium 30210560
2019 Per3 is expressed in the developing mouse cortex; acute knockdown of Per3 by in utero electroporation causes abnormal neuronal positioning (migration defects), impaired axon extension, and impaired dendritic arbor formation; these phenotypes are rescued by RNAi-resistant Per3. In utero electroporation-based knockdown, in situ hybridization, rescue with RNAi-resistant construct, imaging of cortical neuron migration and morphology Scientific reports High 30971765
2014 miR-103 directly targets PER3 (3'UTR) in colorectal cancer cells, reducing PER3 expression; PER3 promotes colorectal cancer cell apoptosis, and PER3 plays a tumor-suppressive role in CRC. Luciferase reporter assay (miR-103 targeting PER3 3'UTR), miR-103 overexpression, apoptosis assays BMB reports Medium 24393525
2019 miR-181a directly targets PER3 in bone marrow and adipose derived stromal cells; enhanced miR-181a expression promotes adipogenesis through PER3 downregulation; knockdown of miR-181a inhibits adipogenesis through regulation of PER3. Luciferase reporter assay (direct targeting), miR-181a overexpression and knockdown, adipogenesis assays in iBMSC and PASC Scientific reports Medium 30670712
2017 Per3-deficient mice exposed to dim light at night exhibit a transient anhedonia-like phenotype (reduced sucrose preference) that wild-type mice do not exhibit; this phenotype is alleviated by imipramine treatment. Per3−/− mice also show a smaller delay in behavioural timing than WT mice during dim light at night. Per3 knockout mice, sucrose preference test (anhedonia), dim light at night protocol, imipramine treatment, corticosterone measurement, hippocampal BDNF expression Scientific reports Medium 28071711
2014 Per3-deficient mice take approximately one additional day to synchronize to a new long photoperiod (16L:8D) compared to wild-type mice, and are more active in the light phase under long photoperiod conditions, suggesting PER3 is involved in suppression of behavioral activity in direct response to light. Per3 knockout mice, running wheel activity recording under different photoperiod and constant darkness conditions BioMed research international Medium 24982860
2022 circMETTL3 directly binds miR-107 which targets PER3; RUNX3 binds to the METTL3 promoter and activates circMETTL3 transcription; PER3 mediates the tumor-suppressive effects of circMETTL3/miR-107 axis in colorectal cancer. Biotin-pulldown, RIP assay, dual luciferase reporter assay, ChIP/EMSA for RUNX3/METTL3 promoter, xenograft mouse model Cell death & disease Medium 35710754
2024 PER3 binds to HIF-1α via its PAS1 domain and promotes HIF-1α ubiquitination and degradation, thereby inhibiting EMT and metastasis in oral squamous cell carcinoma; PER3 promoter hypermethylation at CpG site cg12258811 inhibits PER3 expression; decitabine combined with LW6 upregulated PER3, downregulated HIF-1α, and inhibited lymph node metastasis in nude mice. Co-immunoprecipitation (PER3-HIF-1α interaction), domain mapping (PAS1 domain), ubiquitination assay, bisulfite pyrosequencing for methylation, in vivo xenograft Translational oncology Medium 39733745
2024 GLYR1 transcriptionally activates PER3 by binding to its promoter; knockdown of PER3 alleviates the tumor-suppressive effects of GLYR1 in multiple myeloma cells, indicating GLYR1/PER3 is a functional signaling axis regulating myeloma cell viability and migration. Luciferase reporter assay and chromatin immunoprecipitation (GLYR1 binding to PER3 promoter), PER3 knockdown/overexpression, CCK-8/colony/TUNEL/transwell assays Genomics Medium 38642856
2010 PER3 promoter polymorphisms (including a VNTR at -318 and SNPs at -320 and -319) affect promoter-driven luciferase expression; the TA2G allele combination drives greater expression than GC2A or TA1G combinations; deletion analysis identified two enhancer regions (-703 to -605, and -283 to -80). Luciferase reporter gene assay, deletion reporter constructs, PCR/sequencing of promoter variants Sleep Medium 20469812
2023 PER3 rs772027021 SNP (c.517C>T, p.P173S) in exon 5 induces increased melanin synthesis in melanocytes of affected epithelial tissues; this SNP was identified in all affected individuals of a DUH family and was shown to promote melanocyte proliferation in zebrafish in vivo; cooperation of SASH1 mutation and PER3 SNP synergistically promotes melanin synthesis and melanoma cell proliferation. Whole-exome sequencing, Sanger sequencing, in vitro melanin synthesis assays, in vivo zebrafish melanocyte proliferation phenotyping Journal of molecular medicine Medium 36790533
2012 In mouse strains (BXD family), a promoter insertion/deletion variant in Per3 causes differential protein binding through the Nrf2 transcriptional activator, leading to cis-acting control of Per3 transcript abundance; alcohol treatment increases Per3 expression in the hippocampus, and this effect interacts with acute restraint stress. High-resolution sequence analysis, eQTL mapping, protein binding affinity assays (two alleles vs. Nrf2), ethanol treatment of mice, stress protocol Translational psychiatry Medium 22832735

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep 466 12841365
2007 PER3 polymorphism predicts sleep structure and waking performance. Current biology : CB 367 17346965
2005 Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis 313 15790588
2005 Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it? Sleep 146 15700718
2008 A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder. Neuroscience letters 123 18789374
1995 The Hansenula polymorpha PER3 gene is essential for the import of PTS1 proteins into the peroxisomal matrix. The Journal of biological chemistry 120 7615522
2008 Inter-individual differences in habitual sleep timing and entrained phase of endogenous circadian rhythms of BMAL1, PER2 and PER3 mRNA in human leukocytes. Sleep 119 18517031
2009 Functional magnetic resonance imaging-assessed brain responses during an executive task depend on interaction of sleep homeostasis, circadian phase, and PER3 genotype. The Journal of neuroscience : the official journal of the Society for Neuroscience 105 19553435
2009 PER3 polymorphism predicts cumulative sleep homeostatic but not neurobehavioral changes to chronic partial sleep deprivation. PloS one 103 19516903
2010 Polymorphism in the PER3 promoter associates with diurnal preference and delayed sleep phase disorder. Sleep 95 20469812
1995 PER3, a gene required for peroxisome biogenesis in Pichia pastoris, encodes a peroxisomal membrane protein involved in protein import. The Journal of biological chemistry 90 7738036
2014 Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder. Scientific reports 89 25201053
2007 Age-related change in the association between a polymorphism in the PER3 gene and preferred timing of sleep and waking activities. Journal of sleep research 84 17309758
2011 Sleep quality and diurnal preference in a sample of young adults: associations with 5HTTLPR, PER3, and CLOCK 3111. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 77 21714069
2017 Phenotyping of PER3 variants reveals widespread effects on circadian preference, sleep regulation, and health. Sleep medicine reviews 73 29248294
2011 Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3. The Journal of clinical endocrinology and metabolism 72 22188742
2017 The Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15. Cell reports 69 29186676
2005 Evolution of a length polymorphism in the human PER3 gene, a component of the circadian system. Journal of biological rhythms 58 16275768
2017 Circadian Clock Model Supports Molecular Link Between PER3 and Human Anxiety. Scientific reports 54 28860482
2012 Reduced expression of PER3 is associated with incidence and development of colon cancer. Annals of surgical oncology 53 22350604
2012 PER3 polymorphism and insomnia severity in alcohol dependence. Sleep 53 22467995
2010 Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 52 20625127
2008 PER3 polymorphism and cardiac autonomic control: effects of sleep debt and circadian phase. American journal of physiology. Heart and circulatory physiology 52 18835917
2016 Overexpression of PER3 Inhibits Self-Renewal Capability and Chemoresistance of Colorectal Cancer Stem-Like Cells via Inhibition of Notch and β-Catenin Signaling. Oncology research 50 27983919
2013 Sleep ability mediates individual differences in the vulnerability to sleep loss: evidence from a PER3 polymorphism. Cortex; a journal devoted to the study of the nervous system and behavior 49 24439663
2009 Circadian disruption, Per3, and human cytokine secretion. Integrative cancer therapies 49 19926609
2012 A promoter polymorphism in the Per3 gene is associated with alcohol and stress response. Translational psychiatry 47 22832735
2021 Circadian Rhythm Gene PER3 Negatively Regulates Stemness of Prostate Cancer Stem Cells via WNT/β-Catenin Signaling in Tumor Microenvironment. Frontiers in cell and developmental biology 46 33816508
2014 PER3, a novel target of miR-103, plays a suppressive role in colorectal cancer in vitro. BMB reports 46 24393525
2011 Circadian clock gene Per3 variants influence the postpartum onset of bipolar disorder. European psychiatry : the journal of the Association of European Psychiatrists 46 21316201
2011 Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism. Neurobiology of aging 45 22169200
2014 Association of Per3 length polymorphism with bipolar I disorder and schizophrenia. Neuropsychiatric disease and treatment 42 25525361
2011 PERIOD1 (PER1) has anti-apoptotic effects, and PER3 has pro-apoptotic effects during cisplatin (CDDP) treatment in human gingival cancer CA9-22 cells. European journal of cancer (Oxford, England : 1990) 40 21459569
2014 Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures. Journal of sleep research 39 24635757
2010 Per3, a circadian gene, is required for Chk2 activation in human cells. FEBS letters 37 21070773
2011 Altered sleep and behavioral activity phenotypes in PER3-deficient mice. American journal of physiology. Regulatory, integrative and comparative physiology 34 21957163
2009 Association between specific diurnal preference questionnaire items and PER3 VNTR genotype. Chronobiology international 34 19360490
2017 PTPRS and PER3 methylation levels are associated with childhood obesity: results from a genome-wide methylation analysis. Pediatric obesity 32 28614626
2016 Lack of association between cluster headache and PER3 clock gene polymorphism. The journal of headache and pain 32 26922944
2014 Association between CLOCK, PER3 and CCRN4L with non‑small cell lung cancer in Brazilian patients. Molecular medicine reports 32 24821610
2022 RUNX3-regulated circRNA METTL3 inhibits colorectal cancer proliferation and metastasis via miR-107/PER3 axis. Cell death & disease 30 35710754
2020 Sleep Quality, Sleep Structure, and PER3 Genotype Mediate Chronotype Effects on Depressive Symptoms in Young Adults. Frontiers in psychology 29 32982844
2014 A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 24577121
2015 Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression. Journal of affective disorders 26 26707349
2015 Up-regulation of PER3 Expression Is Correlated with Better Clinical Outcome in Acute Leukemia. Anticancer research 25 26637877
2019 Role of Per3, a circadian clock gene, in embryonic development of mouse cerebral cortex. Scientific reports 24 30971765
2018 Temporal dynamics of cortisol-associated changes in mRNA expression of glucocorticoid responsive genes FKBP5, GILZ, SDPR, PER1, PER2 and PER3 in healthy humans. Psychoneuroendocrinology 22 30522007
2018 Overexpression of PER3 reverses paclitaxel resistance of prostate cancer cells by inhibiting the Notch pathway. European review for medical and pharmacological sciences 20 29771413
2015 Associations of PER3 and RORA Circadian Gene Polymorphisms and Depressive Symptoms in Older Adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20 25892098
2008 Identification of coding polymorphisms in human circadian rhythm genes PER1, PER2, PER3, CLOCK, ARNTL, CRY1, CRY2 and TIMELESS in a multi-ethnic screening panel. DNA sequence : the journal of DNA sequencing and mapping 20 17852344
2017 Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3-/- mice, but not wildtype mice. Scientific reports 19 28071711
2016 A PER3 Polymorphism Interacts with Sleep Duration to Influence Transient Mood States in Women. Journal of circadian rhythms 19 27103936
2019 miR-181a modulates circadian rhythm in immortalized bone marrow and adipose derived stromal cells and promotes differentiation through the regulation of PER3. Scientific reports 18 30670712
2017 Positive association between physical activity and PER3 expression in older adults. Scientific reports 18 28045078
2017 Diurnal preference, mood and the response to morning light in relation to polymorphisms in the human clock gene PER3. Scientific reports 18 28761043
2014 Study of a Functional Polymorphism in the PER3 Gene and Diurnal Preference in a Colombian Sample. The open neurology journal 18 24860629
2014 Per3 length polymorphism in patients with type 2 diabetes mellitus. Hormone molecular biology and clinical investigation 18 25390010
2014 Evolutionary history of the PER3 variable number of tandem repeats (VNTR): idiosyncratic aspect of primate molecular circadian clock. PloS one 15 25222750
2017 Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder. Psychiatry investigation 14 29042894
2017 DEC2 Blocks the Effect of the ARNTL2/NPAS2 Dimer on the Expression of PER3 and DBP. Journal of circadian rhythms 14 30210560
1990 The genetical control of tissue-specific peroxidases,Per-1,Per-2,Per-3,Per-4, andPer-5 in wheat. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 14 24226347
2022 PER3 plays anticancer roles in the oncogenesis and progression of breast cancer via regulating MEK/ERK signaling pathway. Journal of the Chinese Medical Association : JCMA 13 36278918
2019 PER3 variable number tandem repeat (VNTR) polymorphism modulates the circadian variation of the descending pain modulatory system in healthy subjects. Scientific reports 13 31249322
2023 Circadian gene Per3 promotes astroblastoma progression through the P53/BCL2/BAX signalling pathway. Gene 12 37951372
2021 Genetic association of the PERIOD3 (PER3) Clock gene with extreme obesity. Obesity research & clinical practice 11 34215556
2020 A Topological Cluster of Differentially Regulated Genes in Mice Lacking PER3. Frontiers in molecular neuroscience 11 32116548
2016 TFEB regulates PER3 expression via glucose-dependent effects on CLOCK/BMAL1. The international journal of biochemistry & cell biology 11 27373683
2015 Genetic association between PER3 genetic polymorphisms and cancer susceptibility: a meta-analysis. Medicine 11 25837749
2023 Relationship between APOE, PER2, PER3 and OX2R Genetic Variants and Neuropsychiatric Symptoms in Patients with Alzheimer's Disease. International journal of environmental research and public health 10 36901420
2021 Association of occupational stress, period circadian regulator 3 (PER3) gene polymorphism and their interaction with poor sleep quality. Journal of sleep research 10 34060156
2018 PER3 gene regulation of sleep-wake behavior as a function of latitude. Sleep health 10 30442327
2023 The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria. Journal of molecular medicine (Berlin, Germany) 9 36790533
2021 Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3VNTR polymorphisms and gene co-expression. NPJ breast cancer 9 34508103
2016 Lack of Association between Genetic Polymorphism of Circadian Genes (PER2, PER3, CLOCK and OX2R) with Late Onset Depression and Alzheimer's Disease in a Sample of a Brazilian Population (Circadian Genes, Late-Onset Depression and Alzheimer's Disease). Current Alzheimer research 9 27335043
2014 PER2 rs2304672, CLOCK rs1801260, and PER3 rs57875989 polymorphisms are not associated with juvenile myoclonic epilepsy. Epilepsy & behavior : E&B 9 24892753
2024 Association between idiopathic hypersomnia and a genetic variant in the PER3 gene. Journal of sleep research 7 38253863
2023 A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism. Balkan journal of medical genetics : BJMG 7 37265974
2020 Possible Association of PER2/PER3 Variable Number Tandem Repeat Polymorphism Variants with Susceptibility and Clinical Characteristics in Pancreatic Cancer. Genetic testing and molecular biomarkers 7 33393850
2015 Differences in planning performance, a neurocognitive endophenotype, are associated with a functional variant in PER3 gene. Chronobiology international 7 25798540
2014 The effect of different photoperiods in circadian rhythms of per3 knockout mice. BioMed research international 7 24982860
2024 Moderating effects of PER3 gene DNA methylation on the association between problematic mobile phone use and chronotype among Chinese young adults: Focus on gender differences. Journal of behavioral addictions 6 38829707
2024 The influence of PER3 VNTR genotypes on the age of onset in a group of bipolar I disorder patients: an exploratory study. International journal of bipolar disorders 6 38992306
2022 Moderating effects of PER3 gene DNA methylation on the association of sleep quality with mental health in Chinese young adults. Journal of affective disorders 6 36528137
2021 RNA-Seq Analysis Reveals Dendrobium officinale Polysaccharides Inhibit Precancerous Lesions of Gastric Cancer through PER3 and AQP4. Evidence-based complementary and alternative medicine : eCAM 6 34721627
2017 Effects of PER3 clock gene polymorphisms on aging-related changes of the cerebral cortex. Brain structure & function 6 28900721
2024 PER3 suppresses tumor metastasis of oral squamous cell carcinoma by promoting HIF-1α degradation. Translational oncology 5 39733745
2021 Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel. Journal of clinical laboratory analysis 5 33501709
2012 Per3 VNTR polymorphism and chronic heart failure. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 5 23128810
2024 PER3 promoter hypermethylation correlates to the progression of pan-cancer. Clinical epigenetics 4 39402618
2024 DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3. Toxics 4 39771050
2022 PERIOD3 (PER3) VNTR Variant Associated with Seasonal Pattern and Family History in Bipolar Disorder. Psychiatria Danubina 4 36548883
2021 Is There a Link between Circadian Clock Protein PERIOD 3 (PER3) (rs57875989) Variant and the Severity of COVID-19 Infection? Current medical science 4 34542826
2017 Higher scores in the extraversion personality trait are associated with a functional polymorphism in the PER3 gene in healthy subjects. Chronobiology international 4 28055273
2024 Unveiling the Role of Human PER3 Gene Polymorphism (rs57875989) as a Potential Risk Factor in Fibromyalgia Syndrome Patients. Cureus 3 39759625
2024 GLYR1 transcriptionally regulates PER3 expression to promote the proliferation and migration of multiple myeloma. Genomics 2 38642856
2024 Variants in the circadian clock genes PER2 and PER3 associate with familial sleep phase disorders. Chronobiology international 2 38695651
2023 Influence of Environmental Exposure to Steel Waste on Endocrine Dysregulation and PER3 Gene Polymorphisms. International journal of environmental research and public health 2 36981669
2023 Investigation of circadian rhythm gene Per3 in diabetic neuropathy. Nucleosides, nucleotides & nucleic acids 2 38037954
2022 A circadian rhythm gene (PER3) VNTR variant as possible risk factor in cohort of Turkish females with primary dysmenorrhea. Nucleosides, nucleotides & nucleic acids 2 35707903
2023 Actigraphic characterization of sleep and circadian phenotypes of PER3 gene VNTR genotypes. Chronobiology international 1 37691400

Missed literature

Know a paper Affinage missed for PER3? Flag it for the maintainers and the community.

No submissions yet.