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Gene Review

CRY1  -  cryptochrome circadian clock 1

Homo sapiens

Synonyms: Cryptochrome-1, PHLL1
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Disease relevance of CRY1


Psychiatry related information on CRY1

  • Linkage disequilibrium analyses using single SNPs and haplotypes showed no association to bipolar disease.Additional, more powerful, studies involving Cry1 and other circadian clock genes need to be tested before an association of circadian abnormalities with bipolar disorder can be excluded [3].

High impact information on CRY1

  • CRY1 is highly expressed with circadian periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN) [4].
  • Light-independent role of CRY1 and CRY2 in the mammalian circadian clock [5].
  • We find that CRY1 and BMAL1 are phosphoproteins in cultured cells [6].
  • Screening in a phyA null mutant background has identified several blue-light response mutants in pea (Pisum sativum), including one that carries a substitution of a highly conserved glycine residue in the N-terminal photolyase-homologous domain of the pea CRY1 gene [7].
  • Analyses of cry1, phyA, and phyB mutants show that all three photoreceptors contribute to seedling photomorphogenesis under high-irradiance blue light, whereas phyA is the main photoreceptor active under low irradiances [7].

Biological context of CRY1

  • We have now identified a second human gene whose amino acid sequence displays 73% identity to the first one and have named the two genes CRY1 and CRY2, respectively [8].
  • In summary, promoter methylation in the PER1, PER2, or CRY1 circadian genes was detected in about one-third of EC and one-fifth of noncancerous endometrial tissues of 35 paired specimens indicating possible disruption of the circadian clock in the development of EC [9].
  • DNA methylation was found in the promoter sequences of PER1, PER2, and CRY1, but not of other six circadian genes in the ECs and normal tissues examined [9].
  • Phylogenetic analyses show at least 2 rounds of gene duplication at the base of the metazoan radiation, as well as several losses, gave rise to 2 cryptochrome (cry) gene families in insects, a Drosophila-like cry1 gene family and a vertebrate-like cry2 family [10].
  • There was no statistical difference in Bmal1 and Cry1 gene expression and plasma melatonin levels in the control group [11].

Anatomical context of CRY1


Associations of CRY1 with chemical compounds


Regulatory relationships of CRY1


Other interactions of CRY1

  • This article discusses approaches, limitations, and applicable protocols to study the regulation of cellular localization of mammalian clock proteins, with a particular focus on mammalian CRY1 and PER2 proteins [18].
  • Eleven of the 35 EC tissues showed CpG methylation in the promoter sequences of PER1, PER2, or CRY1 [9].

Analytical, diagnostic and therapeutic context of CRY1

  • CRY1 and CRY2 mRNA expression was analyzed in 4-mm diameter punches of macula and midperipheral human retina by quantitative RT-PCR [12].
  • The results showed that the expression of Bmal1 was decreased and Cry1 increased significantly after phototherapy [11].
  • PCR with total DNA from strain J112 and specific primers for cry1, cry2, cry3, cry4, and cyt2A genes revealed that cry1, cry3A, cry4, cry5 and cyt2a genes are present [19].


  1. Cryptochromes and neuronal-activity markers colocalize in the retina of migratory birds during magnetic orientation. Mouritsen, H., Janssen-Bienhold, U., Liedvogel, M., Feenders, G., Stalleicken, J., Dirks, P., Weiler, R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Importance of Cry1 delta-endotoxin domain II loops for binding specificity in Heliothis virescens (L.). Jurat-Fuentes, J.L., Adang, M.J. Appl. Environ. Microbiol. (2001) [Pubmed]
  3. Examination of the clock gene Cryptochrome 1 in bipolar disorder: mutational analysis and absence of evidence for linkage or association. Nievergelt, C.M., Kripke, D.F., Remick, R.A., Sadovnick, A.D., McElroy, S.L., Keck, P.E., Kelsoe, J.R. Psychiatr. Genet. (2005) [Pubmed]
  4. Cryptochrome: the second photoactive pigment in the eye and its role in circadian photoreception. Sancar, A. Annu. Rev. Biochem. (2000) [Pubmed]
  5. Light-independent role of CRY1 and CRY2 in the mammalian circadian clock. Griffin, E.A., Staknis, D., Weitz, C.J. Science (1999) [Pubmed]
  6. The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon. Eide, E.J., Vielhaber, E.L., Hinz, W.A., Virshup, D.M. J. Biol. Chem. (2002) [Pubmed]
  7. Cryptochrome 1 contributes to blue-light sensing in pea. Platten, J.D., Foo, E., Elliott, R.C., Hecht, V., Reid, J.B., Weller, J.L. Plant Physiol. (2005) [Pubmed]
  8. Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteins. Hsu, D.S., Zhao, X., Zhao, S., Kazantsev, A., Wang, R.P., Todo, T., Wei, Y.F., Sancar, A. Biochemistry (1996) [Pubmed]
  9. Promoter methylation in circadian genes of endometrial cancers detected by methylation-specific PCR. Shih, M.C., Yeh, K.T., Tang, K.P., Chen, J.C., Chang, J.G. Mol. Carcinog. (2006) [Pubmed]
  10. Insect cryptochromes: gene duplication and loss define diverse ways to construct insect circadian clocks. Yuan, Q., Metterville, D., Briscoe, A.D., Reppert, S.M. Mol. Biol. Evol. (2007) [Pubmed]
  11. The effect of blue light exposure on the expression of circadian genes: bmal1 and cryptochrome 1 in peripheral blood mononuclear cells of jaundiced neonates. Chen, A., Du, L., Xu, Y., Chen, L., Wu, Y. Pediatr. Res. (2005) [Pubmed]
  12. Expression of the blue-light receptor cryptochrome in the human retina. Thompson, C.L., Rickman, C.B., Shaw, S.J., Ebright, J.N., Kelly, U., Sancar, A., Rickman, D.W. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  13. Expression of haPer1 and haBmal1 in Syrian hamsters: heterogeneity of transcripts and oscillations in the periphery. Tong, Y., Guo, H., Brewer, J.M., Lee, H., Lehman, M.N., Bittman, E.L. J. Biol. Rhythms (2004) [Pubmed]
  14. Evidence of an oscillating peripheral clock in an equine fibroblast cell line and adipose tissue but not in peripheral blood. Murphy, B.A., Vick, M.M., Sessions, D.R., Cook, R.F., Fitzgerald, B.P. Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology. (2006) [Pubmed]
  15. The cryptochrome gene family in pea includes two differentially expressed CRY2 genes. Platten, J.D., Foo, E., Foucher, F., Hecht, V., Reid, J.B., Weller, J.L. Plant Mol. Biol. (2005) [Pubmed]
  16. Photoperiod regulates multiple gene expression in the suprachiasmatic nuclei and pars tuberalis of the Siberian hamster (Phodopus sungorus). Johnston, J.D., Ebling, F.J., Hazlerigg, D.G. Eur. J. Neurosci. (2005) [Pubmed]
  17. Decoding the nightly melatonin signal through circadian clockwork. Lincoln, G.A. Mol. Cell. Endocrinol. (2006) [Pubmed]
  18. Nucleocytoplasmic shuttling of clock proteins. Tamanini, F., Yagita, K., Okamura, H., van der Horst, G.T. Meth. Enzymol. (2005) [Pubmed]
  19. Characterization of Bacillus thuringiensis ser. jordanica (serotype H71), a novel serovariety isolated in Jordan. Khyami-Horani, H., Hajaij, M., Charles, J.F. Curr. Microbiol. (2003) [Pubmed]
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