NPAS2

Summary

Gene Symbol: NPAS2
Description: neuronal PAS domain protein 2
Alias: MOP4, PASD4, bHLHe9, neuronal PAS domain-containing protein 2, PAS domain-containing protein 4, basic-helix-loop-helix-PAS protein MOP4, class E basic helix-loop-helix protein 9, member of PAS protein 4, member of PAS superfamily 4, neuronal PAS2
Species: human
Products:     NPAS2

Top Publications

  1. Nievergelt C, Kripke D, Barrett T, Burg E, Remick R, Sadovnick A, et al. Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:234-41 pubmed
    ..association involving polymorphisms in 10 circadian clock genes (ARNTL, CLOCK, CRY2, CSNK1epsilon, DBP, GSK3beta, NPAS2, PER1, PER2, and PER3) to BPAD...
  2. Lavebratt C, Sjöholm L, Partonen T, Schalling M, Forsell Y. PER2 variantion is associated with depression vulnerability. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:570-581 pubmed publisher
    ..Polymorphisms in the circadian genes NPAS2, ARNTL, and RORA were also suggested to contribute to depression vulnerability...
  3. Rutter J, Reick M, Wu L, McKnight S. Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science. 2001;293:510-4 pubmed
    Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle...
  4. Reick M, Garcia J, Dudley C, McKnight S. NPAS2: an analog of clock operative in the mammalian forebrain. Science. 2001;293:506-9 pubmed
    Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain...
  5. Englund A, Kovanen L, Saarikoski S, Haukka J, Reunanen A, Aromaa A, et al. NPAS2 and PER2 are linked to risk factors of the metabolic syndrome. J Circadian Rhythms. 2009;7:5 pubmed publisher
    ..Our findings link circadian gene variants to the risk factors of the metabolic syndrome, since Npas2 was associated with hypertension (P-value corrected for multiple testing = 0...
  6. Zhou Y, Barnard M, Tian H, Li X, Ring H, Francke U, et al. Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system. Proc Natl Acad Sci U S A. 1997;94:713-8 pubmed
    ..Both proteins, neuronal PAS domain protein (NPAS) 1 and NPAS2, are members of the basic helix-loop-helix-PAS family of transcription factors...
  7. Johansson C, Willeit M, Smedh C, Ekholm J, Paunio T, Kieseppä T, et al. Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference. Neuropsychopharmacology. 2003;28:734-9 pubmed
    ..The complete case-control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (chi(2)=9...
  8. Nicholas B, Rudrasingham V, Nash S, Kirov G, Owen M, Wimpory D. Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis. Mol Psychiatry. 2007;12:581-92 pubmed
    ..We found significant association (P<0.05) for two single-nucleotide polymorphisms in per1 and two in npas2. Analysis of all possible combinations of two-marker haplotypes for each gene showed that in npas2 40 out of the ..
  9. Partonen T, Treutlein J, Alpman A, Frank J, Johansson C, Depner M, et al. Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression. Ann Med. 2007;39:229-38 pubmed
    ..We hypothesized that sequence variations in three genes, including Per2, Arntl, and Npas2, which form a functional unit at the core of the circadian clock, predispose to winter depression...

More Information

Publications107 found, 100 shown here

  1. Chu L, Zhu Y, Yu K, Zheng T, Chokkalingam A, Stanczyk F, et al. Correlation between circadian gene variants and serum levels of sex steroids and insulin-like growth factor-I. Cancer Epidemiol Biomarkers Prev. 2008;17:3268-73 pubmed publisher
    ..insight into these findings, we examined the relationship of five variants of circadian genes, including NPAS2 (rs2305160:G > A), PER1 (rs2585405:G > C), CSNK1E (rs1005473:A > C), PER3 (54-bp repeat length variant), ..
  2. Hannou L, Bélanger Nelson E, O Callaghan E, Dufort Gervais J, Ballester Roig M, Roy P, et al. Regulation of the Neuroligin-1 Gene by Clock Transcription Factors. J Biol Rhythms. 2018;33:166-178 pubmed publisher
    ..We thus aimed to verify whether CLOCK/BMAL1, as well as their homologs NPAS2 and BMAL2, can activate transcription via the Nlgn1 promoter by using luciferase assays in COS-7 cells...
  3. Brzezinski A, Saada A, Miller H, Brzezinski Sinai N, Ben Meir A. Is the aging human ovary still ticking?: Expression of clock-genes in luteinized granulosa cells of young and older women. J Ovarian Res. 2018;11:95 pubmed publisher
    ..The mRNA expression levels of the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2 were analyzed by quantitative polymerase chain reaction...
  4. Paibomesai M, Moghadam H, Ferguson M, Danzmann R. Clock genes and their genomic distributions in three species of salmonid fishes: Associations with genes regulating sexual maturation and cell cycling. BMC Res Notes. 2010;3:215 pubmed publisher
    ..Clock1 duplicates and copies of Clock3 and NPAS2-like genes were partially characterized (genomic sequencing) and mapped using family-based indels/SNPs in rainbow ..
  5. O Neil D, Stewart C, Chu D, Goodspeed D, Gonzalez Rodriguez P, Shope C, et al. Conditional postnatal deletion of the neonatal murine hepatic circadian gene, Npas2, alters the gut microbiome following restricted feeding. Am J Obstet Gynecol. 2017;217:218.e1-218.e15 pubmed publisher
    ..primates and in rodents that fetal and neonatal hepatic expression of the circadian transcription factor, Npas2, is modulated by a high fat maternal diet and plays a critical role in establishing life-long metabolic ..
  6. Li H, Song S, Wang Y, Huang C, Zhang F, Liu J, et al. Low-Grade Inflammation Aggravates Rotenone Neurotoxicity and Disrupts Circadian Clock Gene Expression in Rats. Neurotox Res. 2019;35:421-431 pubmed publisher
    ..and muscle Arnt-like protein-1 (Bmal1), locomotor output cycles kaput (Clock), and neuronal PAS domain protein-2 (Npas2) were decreased in LPS, ROT, and LPS plus ROT groups...
  7. Zhao Q, Zheng G, Yang K, Ao Y, Su X, Li Y, et al. The clock gene PER1 plays an important role in regulating the clock gene network in human oral squamous cell carcinoma cells. Oncotarget. 2016;7:70290-70302 pubmed publisher
    ..PCR result indicated that in vitro and in vivo cancer cells after PER1 knockdown, PER2, DEC1, DEC2, CRY1, CRY2 and NPAS2 were significantly down-regulated at the mRNA level, while PER3, TIM, RORα and REV-ERBα were significantly ..
  8. Gao L, Wang G. Comprehensive bioinformatics analysis identifies several potential diagnostic markers and potential roles of cyclin family members in lung adenocarcinoma. Onco Targets Ther. 2018;11:7407-7415 pubmed publisher
    ..Additionally, genes, including NPAS2, GNG7, CHIA, and SLC2A1, were predicted to be prognosis-related DEGs...
  9. Benna C, Rajendran S, Spiro G, Tropea S, Del Fiore P, Rossi C, et al. Associations of clock genes polymorphisms with soft tissue sarcoma susceptibility and prognosis. J Transl Med. 2018;16:338 pubmed publisher
    ..The minor allele (A) of NPAS2 rs895520 was associated with an increased predisposition to sarcoma of 33% and leiomyosarcoma of 44%...
  10. Gutiérrez Monreal M, Villela L, Baltazar S, Perfecto Avalos Y, Cardineau G, Scott S. A PER3 polymorphism is associated with better overall survival in diffuse large B-cell lymphoma in Mexican population. Cancer Biomark. 2015;15:699-705 pubmed publisher
    ..Sixteen high-risk non-synonymous polymorphisms in circadian genes (CLOCK, CRY2, CSNK1E, CSNK2A1, NPAS2, PER1, PER2, PER3, PPP2CA, and TIM) were genotyped by screening PCR...
  11. Mao W, Zhao C, Ding H, Liang K, Xue J, Chan P, et al. Pyrosequencing analysis of methylation levels of clock genes in leukocytes from Parkinson's disease patients. Neurosci Lett. 2018;668:115-119 pubmed publisher
    DNA methylation of neuronal PAS domain protein 2 (NPAS2) and cryptochrome circadian clock 1 (CRY1) promoters may be associated with Parkinson's disease (PD)...
  12. Lesicka M, Jabłońska E, Wieczorek E, Seroczynska B, Siekierzycka A, Skokowski J, et al. Altered circadian genes expression in breast cancer tissue according to the clinical characteristics. PLoS ONE. 2018;13:e0199622 pubmed publisher
    ..assess the significance of circadian gene expression in breast cancer, we carried out an analysis of CLOCK, BMAL1, NPAS2, PER1, PER2, PER3 and CRY1, CRY2, TIMELESS, CSNK1E expression by the use of the quantitative Real-Time PCR ..
  13. Morinaga K, Sasaki H, Park S, Hokugo A, Okawa H, Tahara Y, et al. Neuronal PAS domain 2 (Npas2) facilitated osseointegration of titanium implant with rough surface through a neuroskeletal mechanism. Biomaterials. 2019;192:62-74 pubmed publisher
    ..We have previously identified an unexpected upregulation of circadian clock molecule neuronal PAS domain 2 (Npas2) in successfully integrated implant with a rough surface...
  14. Wang M, Zhou Z, Khan M, Gao J, Loor J. Clock circadian regulator (CLOCK) gene network expression patterns in bovine adipose, liver, and mammary gland at 3 time points during the transition from pregnancy into lactation. J Dairy Sci. 2015;98:4601-12 pubmed publisher
    ..No interaction was detected for CLOCK, CRY2, PER1, and PER3. In general, the expression of NPAS2, NR1D1, NR2F2, ALAS1, FECH, FBXW11, CCRN4L, PPARA, PPARGC1A, and FGF21 was lower at -10 d but increased postpartum ..
  15. Pellegrino R, Kavakli I, Goel N, Cardinale C, Dinges D, Kuna S, et al. A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans. Sleep. 2014;37:1327-36 pubmed publisher
    ..This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro...
  16. Yoshii K, Tajima F, Ishijima S, Sagami I. Changes in pH and NADPH regulate the DNA binding activity of neuronal PAS domain protein 2, a mammalian circadian transcription factor. Biochemistry. 2015;54:250-9 pubmed publisher
    Neuronal PAS domain protein 2 (NPAS2) is a core clock transcription factor that forms a heterodimer with BMAL1 to bind the E-box in the promoter of clock genes and is regulated by various environmental stimuli such as heme, carbon ..
  17. Cadenas C, van de Sandt L, Edlund K, Lohr M, Hellwig B, Marchan R, et al. Loss of circadian clock gene expression is associated with tumor progression in breast cancer. Cell Cycle. 2014;13:3282-91 pubmed publisher
    ..Higher expression of several clock genes (e.g., CLOCK, PER1, PER2, PER3, CRY2, NPAS2 and RORC) was found to be associated with longer MFS in univariate Cox regression analyses (HR<1 and FDR-..
  18. He D, An Y, Li Y, Wang J, Wu G, Chen L, et al. RNA sequencing reveals target genes of temporomandibular joint osteoarthritis in rats after the treatment of low-intensity pulsed ultrasound. Gene. 2018;672:126-136 pubmed publisher
    ..Some were reported for the first time in TMJ-OA, such as circadian gene (Per-2, Dbp, Npas2 and Arntl)...
  19. Efimov I, Parkin G, Millett E, Glenday J, Chan C, Weedon H, et al. A simple method for the determination of reduction potentials in heme proteins. FEBS Lett. 2014;588:701-4 pubmed publisher
    ..use the method to determine the reduction potentials for the PAS-A domains of the regulatory heme proteins human NPAS2 (Em=-115 mV ± 2 mV, pH 7.0) and human CLOCK (Em=-111 mV ± 2 mV, pH 7.0)...
  20. Qian X, Khammanivong A, Song J, Teferi F, Upadhyaya P, Dickerson E, et al. RNA-sequencing studies identify genes differentially regulated during inflammation-driven lung tumorigenesis and targeted by chemopreventive agents. Inflamm Res. 2015;64:343-61 pubmed publisher
    ..cytokines, chemokines, putative oncogenes and tumor suppressor genes and Ros1, AREG, EREG, Cyp1a1, Arntl, and Npas2. To our knowledge, this is the first report that provides insight into genes that are differentially expressed ..
  21. Luciano A, Zhou W, Santana J, Kyriakides C, Velazquez H, Sessa W. CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian gene expression in peripheral tissues. J Biol Chem. 2018;293:9126-9136 pubmed publisher
    ..that ClockS845A mice have diminished expression of Per2, Reverba, Dbp, and Npas2 in skeletal muscle and Per2, Reverba, Dbp, Per1, Rora, and Npas2 in the liver during the ..
  22. Wu P, Chu W, Liu X, Guo X, Zhang J. The Influence of Short-term Fasting on Muscle Growth and Fiber Hypotrophy Regulated by the Rhythmic Expression of Clock Genes and Myogenic Factors in Nile Tilapia. Mar Biotechnol (NY). 2018;20:750-768 pubmed publisher
    ..clockb, ciarta, and aanat2 displayed a daily rhythmicity in normal daily cycle, while arntl2, cry1a, cry1b, npas2, nr1d2b, per2, per3, rorαb, clocka, clockb, nfil3, cipca, and cipcb exhibited daily rhythmicity in the fasting ..
  23. Minegishi S, Sagami I, Negi S, Kano K, Kitagishi H. Circadian clock disruption by selective removal of endogenous carbon monoxide. Sci Rep. 2018;8:11996 pubmed publisher
    ..Previous studies have demonstrated that core transcriptional factors, NPAS2 and CLOCK, in the TTFL can reversibly bind carbon monoxide (CO) in vitro...
  24. Suter M, Bocock P, Showalter L, Hu M, Shope C, McKnight R, et al. Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates. FASEB J. 2011;25:714-26 pubmed publisher
    ..machinery are transcribed in the nonhuman primate fetal liver in an intact phase-antiphase fashion and that Npas2, a paralog of the Clock transcription factor, serves as the rate-limiting transcript by virtue of its relative low ..
  25. Rabstein S, Harth V, Justenhoven C, Pesch B, Plöttner S, Heinze E, et al. Polymorphisms in circadian genes, night work and breast cancer: results from the GENICA study. Chronobiol Int. 2014;31:1115-22 pubmed publisher
    ..Associations between seven polymorphisms in circadian genes (CLOCK, NPAS2, ARTNL, PER2 and CRY2), genes of melatonin biosynthesis and signaling (AANAT and MTNR1B) and breast cancer were ..
  26. Trivedi A, Kumar J, Rani S, Kumar V. Annual life history-dependent gene expression in the hypothalamus and liver of a migratory songbird: insights into the molecular regulation of seasonal metabolism. J Biol Rhythms. 2014;29:332-45 pubmed publisher
    ..The mRNA levels of circadian genes involved in metabolism (Bmal1, Clock, Npas2, Rorα, and Rev-erbα) and of genes that encode for proteins/enzymes involved in the regulation of glucose (..
  27. Karaś K, Sałkowska A, Walczak Drzewiecka A, Ryba K, Dastych J, Bachorz R, et al. The cardenolides strophanthidin, digoxigenin and dihydroouabain act as activators of the human ROR?/ROR?T receptors. Toxicol Lett. 2018;295:314-324 pubmed publisher
    ..These compounds increased G6PC and NPAS2 expression in HepG2 cells, accompanied by increased occupancy of ROR? within the promoters of these genes...
  28. Herichova I, Zsoldosova K, Vesela A, Zeman M. Effect of angiotensin II infusion on rhythmic clock gene expression and local renin-angiotensin system in the aorta of Wistar rats. Endocr Regul. 2014;48:144-51 pubmed
    ..We observed a significant phase advance in per2 and npas2 mRNA rhythms and decreased mesor of npas2 rhythmic expression in the aorta of angiotensin II-treated rats compared ..
  29. Leu H, Chung C, Lin S, Chiang K, Yang H, Ho H, et al. Association of circadian genes with diurnal blood pressure changes and non-dipper essential hypertension: a genetic association with young-onset hypertension. Hypertens Res. 2015;38:155-62 pubmed publisher
    ..Five tag SNPs within five loci, including rs3888170 in NPAS2, rs6431590 in PER2, rs1410225 in RORββ, rs3816358 in BMAL1 and rs10519096 in RORα, were significantly ..
  30. Reszka E, Przybek M, Muurlink O, Pepłońska B. Circadian gene variants and breast cancer. Cancer Lett. 2017;390:137-145 pubmed publisher
    ..We summarize fifteen epidemiological studies, including five studies on shift work that have indicated BMAL1, BMAL2, CLOCK, NPAS2, CRY1, CRY2, PER1, PER3 and TIMELESS as a candidate breast cancer risk variants.
  31. Lee S, Zhang Y, Tsuchiya H, Smalling R, Jetten A, Wang L. Small heterodimer partner/neuronal PAS domain protein 2 axis regulates the oscillation of liver lipid metabolism. Hepatology. 2015;61:497-505 pubmed publisher
    ..proliferator-activated receptor-γ, coactivator 1 (Pgc-1α), neuronal PAS domain-containing protein 2 (Npas2), and retinoic acid-related orphan receptor (Ror)α/γ were sharply induced in Shp(-/-) liver...
  32. Yang Z, Matsumoto A, Nakayama K, Jimbo E, Kojima K, Nagata K, et al. Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients. Brain Dev. 2016;38:91-9 pubmed publisher
    ..Some circadian-relevant genes have been associated with ASD (e.g., PER1, PER2, NPAS2, MTNR1A, and MTNR1B)...
  33. Yeim S, Boudebesse C, Etain B, Belliviera F. [Circadian markers and genes in bipolar disorder]. Encephale. 2015;41:S38-44 pubmed publisher
    ..showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε...
  34. Lin E, Kuo P, Liu Y, Yang A, Kao C, Tsai S. Effects of circadian clock genes and environmental factors on cognitive aging in old adults in a Taiwanese population. Oncotarget. 2017;8:24088-24098 pubmed publisher
    ..0017), NPAS2 rs17655330 (p = 0.0013), RORA rs13329238 (p = 0.0009), and RORB rs10781247 (p = 7.9 x 10-5)...
  35. Markt S, Valdimarsdottir U, Shui I, Sigurdardottir L, Rider J, Tamimi R, et al. Circadian clock genes and risk of fatal prostate cancer. Cancer Causes Control. 2015;26:25-33 pubmed publisher
    ..01, and 0.05 for AGES-Reykjavik, HPFS, and PHS, respectively). In AGES-Reykjavik, SNPs in TIMELESS (four SNPs), NPAS2 (six SNPs), PER3 (two SNPs) and CSNK1E (one SNP) were nominally associated with 6-sulfatoxymelatonin levels...
  36. Sun H, Li S, Chen F, Zhang Y, Li P, Jin M, et al. Diurnal neurobiological alterations after exposure to clozapine in first-episode schizophrenia patients. Psychoneuroendocrinology. 2016;64:108-16 pubmed publisher
    ..controls, schizophrenia patients presented disruptions in diurnal rhythms of the expression of PER1, PER3, and NPAS2 and the release of orexin, accompanied by a delayed phase in the expression of PER2, decreases in PER3 and NPAS2 ..
  37. Trivedi A, Malik S, Rani S, Kumar V. Pinealectomy abolishes circadian behavior and interferes with circadian clock gene oscillations in brain and liver but not retina in a migratory songbird. Physiol Behav. 2016;156:156-63 pubmed publisher
    ..Whereas activity-rest pattern was monitored continuously, the mRNA expressions of clock genes (bmal1, clock, npas2, per2, cry1, rorα, reverα) were measured in the retina, hypothalamus, telencephalon, optic tectum and liver ..
  38. Stuber E, Baumgartner C, Dingemanse N, Kempenaers B, Mueller J. Genetic Correlates of Individual Differences in Sleep Behavior of Free-Living Great Tits (Parus major). G3 (Bethesda). 2016;6:599-607 pubmed publisher
    ..Microsatellites in the CLOCK and NPAS2 clock genes exhibited an association with sleep duration relative to night length, and morning latency to exit the ..
  39. Landgraf D, Wang L, Diemer T, Welsh D. NPAS2 Compensates for Loss of CLOCK in Peripheral Circadian Oscillators. PLoS Genet. 2016;12:e1005882 pubmed publisher
    ..Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN), the master circadian pacemaker, CLOCK-deficient ..
  40. Herichova I, Hasáková K, Lukacova D, Mravec B, Horvathova L, Kavická D. Prefrontal cortex and dorsomedial hypothalamus mediate food reward-induced effects via npas2 and egr1 expression in rat. Physiol Res. 2017;66:S501-S510 pubmed
    ..dorsomedial hypothalamus (DMH) and liver at the time of reward delivery indicated transcriptional factors egr1 and npas2 as possible mediators of food reward effects...
  41. Palmieri O, Mazzoccoli G, Bossa F, Maglietta R, Palumbo O, Ancona N, et al. Systematic analysis of circadian genes using genome-wide cDNA microarrays in the inflammatory bowel disease transcriptome. Chronobiol Int. 2015;32:903-16 pubmed publisher
    ..Among the core clock genes ARNTL2 and RORA were up-regulated, while CSNK2B, NPAS2, PER1 and PER3 were down-regulated in CD specimens...
  42. Koczor C, Ludlow I, Hight R, Jiao Z, Fields E, Ludaway T, et al. Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart. Toxicol Sci. 2015;148:183-91 pubmed publisher
    ..After 35 days, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) persisted to be differentially expressed...
  43. Olkkonen J, Kouri V, Hynninen J, Konttinen Y, Mandelin J. Differentially Expressed in Chondrocytes 2 (DEC2) Increases the Expression of IL-1β and Is Abundantly Present in Synovial Membrane in Rheumatoid Arthritis. PLoS ONE. 2015;10:e0145279 pubmed publisher
    ..circulating serum cortisol, melatonin and IL-6, as well as disturbance in the expression of clock genes ARNTL2 and NPAS2. In humans, TNFα increases the expression ARNTL2 and NPAS2 but paradoxically suppresses clock output genes DPB ..
  44. Mang G, La Spada F, Emmenegger Y, Chappuis S, Ripperger J, Albrecht U, et al. Altered Sleep Homeostasis in Rev-erbα Knockout Mice. Sleep. 2016;39:589-601 pubmed publisher
    ..Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain...
  45. Chun L, Woodruff E, Morton S, Hinds L, Spencer R. Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats. J Biol Rhythms. 2015;30:417-36 pubmed publisher
    The molecular circadian clock is a self-regulating transcription/translation cycle of positive (Bmal1, Clock/Npas2) and negative (Per1,2,3, Cry1,2) regulatory components...
  46. Wu P, Li Y, Cheng J, Chen L, Zhu X, Feng Z, et al. Daily rhythmicity of clock gene transcript levels in fast and slow muscle fibers from Chinese perch (Siniperca chuatsi). BMC Genomics. 2016;17:1008 pubmed
    ..In the present study, the molecular clock components (clock, arntl1/2, cry1/2/3, cry-dash, npas2, nr1d1/2, per1/2/3, ror? and tim genes) and their daily transcription levels were characterized in slow and fast ..
  47. Andersen M, Black M, Campbell J, Pendse S, Clewell H, Pottenger L, et al. Combining transcriptomics and PBPK modeling indicates a primary role of hypoxia and altered circadian signaling in dichloromethane carcinogenicity in mouse lung and liver. Toxicol Appl Pharmacol. 2017;332:149-158 pubmed publisher
    ..primarily transcription factors - showed strong concentration-related response at higher concentrations (Arntl, Npas2, and Clock were down-regulated; Cry2, Wee1, Bhlhe40, Per3, Nr1d1, Nr1d2 and Dbp) were up-regulated with similar ..
  48. Jacovetti C, Rodríguez Trejo A, Guay C, Sobel J, Gattesco S, Petrenko V, et al. MicroRNAs modulate core-clock gene expression in pancreatic islets during early postnatal life in rats. Diabetologia. 2017;60:2011-2020 pubmed publisher
    ..We found up to a sixfold-change in the 24 h transcriptional oscillations and overall expression of Clock, Npas2, Bmal1, Bmal2, Rev-erbα, Per1, Per2, Per3 and Cry2 between newborn and adult rat islets...
  49. Mocellin S, Tropea S, Benna C, Rossi C. Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies. BMC Med. 2018;16:20 pubmed publisher
    ..CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for ..
  50. Gao Q, Zhou L, Yang S, Cao J. A novel role of microRNA 17-5p in the modulation of circadian rhythm. Sci Rep. 2016;6:30070 pubmed publisher
    ..In addition, miR-17-5p suppressed the expression of Npas2. At the cellular level, bidirectional changes in miR-17-5p or CLOCK resulted in CRY1 elevation...
  51. Nawrot T, Saenen N, Schenk J, Janssen B, Motta V, Tarantini L, et al. Placental circadian pathway methylation and in utero exposure to fine particle air pollution. Environ Int. 2018;114:231-241 pubmed publisher
    ..we quantified placental methylation of CpG sites within the promoter regions of the following genes: CLOCK, BMAL1, NPAS2, CRY1-2 and PER1-3 using bisulfite-PCR-pyrosequencing. Daily PM2...
  52. Liu C, Su L, Tsai W, Sun H, Lee H, Wong C. Hylan G-F 20 attenuates posttraumatic osteoarthritis progression: Association with upregulated expression of the circardian gene NPAS2. Life Sci. 2015;141:20-4 pubmed publisher
    ..of posttraumatic osteoarthritis (PTOA) and the expression of the circadian genes neuronal PAS domain protein 2 (NPAS2) and period 2 (Per2)...
  53. Li H, Fan X, Luo Y, Song S, Liu J, Fan Q. Repeated manganese administration produced abnormal expression of circadian clock genes in the hypothalamus and liver of rats. Neurotoxicology. 2017;62:39-45 pubmed publisher
    ..and muscle Arnt-like protein-1 (Bmal1), locomotor output cycles kaput (Clock) and neuronal PAS domain protein2 (Npas2), and clock feedback gene cryptochrome1 (Cry1), period genes (Per1 and Per2) in the hypothalamus and liver were ..
  54. Kondratov R, Kondratova A, Lee C, Gorbacheva V, Chernov M, Antoch M. Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES. Cell Cycle. 2006;5:890-5 pubmed
    Mammalian CLOCK(NPAS2), BMAL1 and CRYPTOCHROMEs are core components of the circadian oscillatory mechanism. The active CLOCK/BMAL1 or NPAS2/BMAL1 complexes regulate expression of numerous genes including two Cryptochromes...
  55. Zhu Y, Leaderer D, Guss C, Brown H, Zhang Y, Boyle P, et al. Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma. Int J Cancer. 2007;120:432-5 pubmed
    ..nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk...
  56. Yi C, Mu L, de la Longrais I, Sochirca O, Arisio R, Yu H, et al. The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer. Breast Cancer Res Treat. 2010;120:663-9 pubmed publisher
    Mounting evidence suggests that neuronal PAS domain protein 2 (NPAS2) and other circadian genes are involved in tumorigenesis and tumor growth, possibly through their control of cancer-related biologic pathways...
  57. Allebrandt K, Teder Laving M, Akyol M, Pichler I, Muller Myhsok B, Pramstaller P, et al. CLOCK gene variants associate with sleep duration in two independent populations. Biol Psychiatry. 2010;67:1040-7 pubmed publisher
    ..This adds another putative function for CLOCK besides its possible involvement in circadian timing, depression, obesity, and personality. ..
  58. Smith A, Fang H, Whistler T, Unger E, Rajeevan M. Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome. Neuropsychobiology. 2011;64:183-94 pubmed publisher
    ..Two genes, glutamate receptor, ionotropic, kinase 2 (GRIK2) and neuronal PAS domain protein 2 (NPAS2), were identified by both SNP and gene expression analyses...
  59. Jung J, Lee H, Cho C, Kang S, Yoon H, Park Y, et al. Association between restless legs syndrome and CLOCK and NPAS2 gene polymorphisms in schizophrenia. Chronobiol Int. 2014;31:838-44 pubmed publisher
    ..We investigated whether CLOCK and NPAS2 gene polymorphisms are associated with RLS in schizophrenic patients on antipsychotics because RLS symptoms ..
  60. Xue X, Liu F, Han Y, Li P, Yuan B, Wang X, et al. Silencing NPAS2 promotes cell growth and invasion in DLD-1 cells and correlated with poor prognosis of colorectal cancer. Biochem Biophys Res Commun. 2014;450:1058-62 pubmed publisher
    ..Neuronal PAS domain protein2 (NPAS2), which is the largest circadian gene, has been proved to be a novel prognostic biomarker in breast cancer and non-..
  61. Rana S, Shahid A, Ullah H, Mahmood S. Lack of association of the NPAS2 gene Ala394Thr polymorphism (rs2305160:G>A) with risk of chronic lymphocytic leukemia. Asian Pac J Cancer Prev. 2014;15:7169-74 pubmed
    b>NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis...
  62. Gu F, Zhang H, Hyland P, Berndt S, Gapstur S, Wheeler W, et al. Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia. Int J Cancer. 2017;141:1794-1802 pubmed publisher
    ..00625). The two most significant genes were NPAS2 (pgene  = 0.0062) and AANAT (pgene  = 0...
  63. McNamara P, Seo S, Rudic R, Sehgal A, Chakravarti D, Fitzgerald G. Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. Cell. 2001;105:877-89 pubmed
    ..We report a hormone-dependent interaction of the nuclear receptors, RAR alpha and RXR alpha, with CLOCK and MOP4. These interactions negatively regulate CLOCK/MOP4:BMAL1-mediated transcriptional activation of clock gene ..
  64. Zhu Y, Stevens R, Hoffman A, FitzGerald L, Kwon E, Ostrander E, et al. Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study. Cancer Res. 2009;69:9315-22 pubmed publisher
    ..in CRY1; rs2292912 in CRY2; rs7950226 in ARNTL; rs11133373 in CLOCK; and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate cancer (either overall risk or risk of aggressive ..
  65. Utge S, Soronen P, Loukola A, Kronholm E, Ollila H, Pirkola S, et al. Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance. PLoS ONE. 2010;5:e9259 pubmed publisher
    ..These findings support a connection between circadian genes and gender-dependent depression and defective sleep regulation. ..
  66. Ramasamy R, Bakırcıoğlu M, Cengiz C, Karaca E, Scovell J, Jhangiani S, et al. Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia. Fertil Steril. 2015;104:286-91 pubmed publisher
    ..A novel nonsynonymous mutation in the neuronal PAS-2 domain (NPAS2) was identified in a consanguineous family from Turkey...
  67. OZBURN A, KERN J, Parekh P, Logan R, Liu Z, Falcon E, et al. NPAS2 Regulation of Anxiety-Like Behavior and GABAA Receptors. Front Mol Neurosci. 2017;10:360 pubmed publisher
    ..Neuronal PAS Domain Protein 2 (NPAS2) is a core component of the molecular clock that acts as a transcription factor and is highly expressed in reward- ..
  68. Sjöholm L, Kovanen L, Saarikoski S, Schalling M, Lavebratt C, Partonen T. CLOCK is suggested to associate with comorbid alcohol use and depressive disorders. J Circadian Rhythms. 2010;8:1 pubmed publisher
    ..Together with previous reports it indicates that the CLOCK variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD. ..
  69. Yuan P, Wang S, Zhou F, Wan S, Yang Y, Huang X, et al. Functional polymorphisms in the NPAS2 gene are associated with overall survival in transcatheter arterial chemoembolization-treated hepatocellular carcinoma patients. Cancer Sci. 2014;105:825-32 pubmed publisher
    ..However, the association between functional single nucleotide polymorphisms (SNPs) in circadian gene NPAS2 and the overall survival of HCC patients treated with transcatheter arterial chemoembolization (TACE) has never ..
  70. Chu L, Zhu Y, Yu K, Zheng T, Yu H, Zhang Y, et al. Variants in circadian genes and prostate cancer risk: a population-based study in China. Prostate Cancer Prostatic Dis. 2008;11:342-8 pubmed
    ..These variants included CRY2 rs1401417:G>C, CSNK1E rs1005473:A>C, NPAS2 rs2305160:G>A, PER1 rs2585405:G>C and PER3 54-bp repeat length variant...
  71. Kovanen L, Saarikoski S, Aromaa A, Lonnqvist J, Partonen T. ARNTL (BMAL1) and NPAS2 gene variants contribute to fertility and seasonality. PLoS ONE. 2010;5:e10007 pubmed publisher
    ..Single-nucleotide polymorphisms in the ARNTL, ARNTL2, CLOCK and NPAS2 genes were genotyped in 511 individuals...
  72. Kovanen L, Saarikoski S, Haukka J, Pirkola S, Aromaa A, Lonnqvist J, et al. Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption. Alcohol Alcohol. 2010;45:303-11 pubmed publisher
    ..04) and NPY Pro7 decreased (P = 0.01) the risk of alcohol dependence. ARNTL, ARNTL2, VIP and ADCYAP1 were indicated as having influence on alcohol use or abuse. The role of DRD2 and NPY on alcohol dependence was also supported. ..
  73. Kim H, Lee H, Cho C, Kang S, Yoon H, Park Y, et al. Association of CLOCK, ARNTL, and NPAS2 gene polymorphisms and seasonal variations in mood and behavior. Chronobiol Int. 2015;32:785-91 pubmed publisher
    ..In this study, we investigated polymorphisms in the CLOCK, ARNTL, and NPAS2 genes in relation to seasonal variation in 507 healthy young adults...
  74. Liu L, Jiang G, Peng Z, Li Y, Li J, Zou L, et al. The effect of high fat diet on daily rhythm of the core clock genes and muscle functional genes in the skeletal muscle of Chinese soft-shelled turtle (Trionyx sinensis). Comp Biochem Physiol B Biochem Mol Biol. 2017;213:17-27 pubmed publisher
    ..the feeding trial experiment, we measured the daily expression levels of 17 core clock genes (Clock, Bmal1/2, NPAS2, Tim, Cry1/2, Per1/2, DBP, AANAT, NIFL3, BHLHE40, NR1D2, RORA, RORB, RORC) and 12 muscle functional genes (FBXO32, ..
  75. Curtis A, Seo S, Westgate E, Rudic R, Smyth E, Chakravarti D, et al. Histone acetyltransferase-dependent chromatin remodeling and the vascular clock. J Biol Chem. 2004;279:7091-7 pubmed
    ..and histone acetyltransferases, p300/CBP, PCAF, and ACTR associate with the bHLH-PAS proteins, CLOCK and NPAS2, to regulate positively clock gene expression...
  76. Bhatti P, Doody M, Rajaraman P, Alexander B, Yeager M, Hutchinson A, et al. Novel breast cancer risk alleles and interaction with ionizing radiation among U.S. radiologic technologists. Radiat Res. 2010;173:214-24 pubmed publisher
    ..Even though a complete understanding of the way(s) in which these variants may increase breast cancer risk remains elusive, this approach may yield clues for further investigation. ..
  77. Partonen T. Clock gene variants in mood and anxiety disorders. J Neural Transm (Vienna). 2012;119:1133-45 pubmed
    ..of RORB (rs7022435, rs3750420, rs1157358, rs3903529) and NR1D1 (rs2314339) with bipolar disorder, and those of NPAS2 (rs11541353) and CRY2 (rs10838524) with seasonal affective disorder or winter depression...
  78. Michel A, Choudhury K, Firth A, Ingolia N, Atkins J, Baranov P. Observation of dually decoded regions of the human genome using ribosome profiling data. Genome Res. 2012;22:2219-29 pubmed publisher
  79. Geoffroy P, Lajnef M, Bellivier F, Jamain S, Gard S, Kahn J, et al. Genetic association study of circadian genes with seasonal pattern in bipolar disorders. Sci Rep. 2015;5:10232 pubmed publisher
    ..A SP in BD was nominally associated with 14 SNPs identified in 6 circadian genes: NPAS2, CRY2, ARNTL, ARNTL2, RORA and RORB...
  80. Hogenesch J, Gu Y, Jain S, Bradfield C. The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci U S A. 1998;95:5474-9 pubmed
    ..We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia-inducible factor 1alpha (HIF1alpha), and HIF2alpha...
  81. Garcia J, Zhang D, Estill S, Michnoff C, Rutter J, Reick M, et al. Impaired cued and contextual memory in NPAS2-deficient mice. Science. 2000;288:2226-30 pubmed
    Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PAS domain transcription factor expressed in multiple regions of the vertebrate brain...
  82. Crumbley C, Wang Y, Kojetin D, Burris T. Characterization of the core mammalian clock component, NPAS2, as a REV-ERBalpha/RORalpha target gene. J Biol Chem. 2010;285:35386-92 pubmed publisher
    ..BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription ..
  83. Evans D, Parimi N, Nievergelt C, Blackwell T, Redline S, Ancoli Israel S, et al. Common genetic variants in ARNTL and NPAS2 and at chromosome 12p13 are associated with objectively measured sleep traits in the elderly. Sleep. 2013;36:431-46 pubmed publisher
    ..22, P = 0.02; rs2238114: ? = -0.50, P = 5 × 10(-8)). In MrOS participants, SNPs in ARNTL and NPAS2, genes coding for binding partners, were associated with later sleep and wake onset time (sleep onset time: ARNTL ..
  84. Soria V, Martínez Amorós E, Escaramis G, Valero J, Pérez Egea R, Garcia C, et al. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology. 2010;35:1279-89 pubmed publisher
    ..SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major ..
  85. Wang F, Hu Z, Yang R, Tang J, Liu Y, Hemminki K, et al. A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk. Breast Cancer Res Treat. 2011;127:769-75 pubmed publisher
    ..A single nucleotide polymorphism (SNP) rs2305160 in Neuronal PAS domain protein 2 (NPAS2), the largest circadian gene, was identified as a breast cancer susceptibility locus...
  86. Truong T, Liquet B, Menegaux F, Plancoulaine S, Laurent Puig P, Mulot C, et al. Breast cancer risk, nightwork, and circadian clock gene polymorphisms. Endocr Relat Cancer. 2014;21:629-38 pubmed publisher
    ..In this subpopulation, we also reported an association with rs11932595 in CLOCK, and with CLOCK, RORA, and NPAS2 in the analyses at the gene level...
  87. Reszka E, Wieczorek E, Przybek M, Jabłońska E, Kałużny P, Bukowska Damska A, et al. Circadian gene methylation in rotating-shift nurses: a cross-sectional study. Chronobiol Int. 2017;:1-11 pubmed publisher
    ..reaction assays were used to assess promoter CpG methylation in PER1, PER2, PER3, CRY1, CRY2, BMAL1, CLOCK, and NPAS2 in genomic DNA from whole blood of 347 women having a rotating-shift work schedule and 363 women working days only...
  88. Rozan L, El Deiry W. Identification and characterization of proteins interacting with Traf4, an enigmatic p53 target. Cancer Biol Ther. 2006;5:1228-35 pubmed
  89. Hoffman A, Zheng T, Ba Y, Zhu Y. The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage response. Mol Cancer Res. 2008;6:1461-8 pubmed publisher
    ..studies recently conducted by our lab have shown that a missense mutation in neuronal PAS domain protein 2 (NPAS2), a core circadian gene and transcriptional regulator, is significantly associated with risk of breast cancer and ..
  90. OZBURN A, Falcon E, Twaddle A, Nugent A, Gillman A, Spencer S, et al. Direct regulation of diurnal Drd3 expression and cocaine reward by NPAS2. Biol Psychiatry. 2015;77:425-433 pubmed publisher
    ..We used mice with a mutation in Npas2 and adeno-associated virus-short hairpin RNA mediated knockdown of Npas2 and Clock in the nucleus accumbens (NAc)...
  91. Franzoni A, Markova Car E, Dević Pavlić S, Jurisic D, Puppin C, Mio C, et al. A polymorphic GGC repeat in the NPAS2 gene and its association with melanoma. Exp Biol Med (Maywood). 2017;242:1553-1558 pubmed publisher
    ..One of these circadian genes, NPAS2, encodes for a member of the bHLH-PAS class of transcription factors and is expressed in the forebrain and in some ..
  92. Bukowska Damska A, Reszka E, Kaluzny P, Wieczorek E, Przybek M, Zienolddiny S, et al. Sleep quality and methylation status of core circadian rhythm genes among nurses and midwives. Chronobiol Int. 2017;:1-13 pubmed publisher
    ..and the levels of 5-methylcytosine in the promoter regions of PER1, PER2, PER3, BMAL1, CLOCK, CRY1 CRY2 and NPAS2 genes, taking into account rotating night work and chronotype as potential confounders or modifiers...