CRY2 Gene: Cryptochrome Circadian Regulator 2
A core circadian clock component implicated in metabolic, psychiatric, and cancer-related disorders
Gene Information Card
| Symbol | CRY2 |
|---|---|
| Full Name | Cryptochrome Circadian Regulator 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p11.2 |
| NCBI Gene ID | 1408 ncbi.nlm.nih.gov/gene/1408 |
| Ensembl ID | ENSG00000121671 |
| UniProt ID | Q49AN0 |
| OMIM ID | 603732 |
| HGNC ID | 2385 |
| Aliases | PHLL2, HCRY2 |
Description
The CRY2 gene encodes a flavin adenine dinucleotide (FAD)-binding protein that is a core component of the circadian clock. It forms a complex with CLOCK and ARNTL/BMAL1, repressing their transcriptional activity and thereby regulating the daily rhythms of gene expression. CRY2 is involved in diverse processes including metabolism, immune response, and cell proliferation. Mutations and dysregulation of CRY2 have been linked to familial delayed sleep phase disorder, metabolic syndrome, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Delayed Sleep Phase Disorder (DSPD) | Altered CRY2 function disrupts circadian period length, leading to phase delay in sleep-wake cycle. | ClinVar: rs7947801 (c.1786C>T, p.Arg596Cys) associated with DSPD; OMIM #614163. |
| Type 2 Diabetes | CRY2 variants affect insulin secretion and glucose metabolism via circadian regulation of pancreatic beta cells. | ClinVar: rs11605924 (intronic) associated with type 2 diabetes in GWAS; PMID: 20081858. |
| Major Depressive Disorder (MDD) | CRY2 expression changes in brain regions affect mood regulation and circadian rhythm stability. | ClinVar: rs10838524 (intronic) associated with MDD; PMID: 23933820. |
| Cancer (various types) | CRY2 acts as a tumor suppressor; loss of function leads to uncontrolled cell proliferation and genomic instability. | COSMIC: CRY2 mutations found in colorectal, breast, and lung cancers; PMID: 25926053. |
| Bipolar Disorder | CRY2 variants may influence circadian phase and mood episodes. | ClinVar: rs7947801 (c.1786C>T) reported in bipolar disorder; PMID: 15678188. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 10.2 | Medium |
| Liver | 8.5 | Medium |
| Pancreas | 6.1 | Low |
| Adipose tissue | 5.3 | Low |
| Muscle (skeletal) | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 12.3 | High expression; used in circadian studies |
| HepG2 (liver cancer) | 9.7 | Moderate expression; circadian regulation |
| MCF7 (breast cancer) | 7.2 | Low expression; altered in cancer |
| A549 (lung cancer) | 6.5 | Low expression; potential tumor suppressor |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1786C>T (p.Arg596Cys) | Missense | Rare (MAF 0.0004) | Alters FAD binding, affects circadian period; associated with DSPD. |
| c.819C>T (p.Ser273=) | Synonymous | Common (MAF 0.12) | No known effect; may affect splicing. |
| c.1259A>G (p.Tyr420Cys) | Missense | Rare (MAF 0.0001) | Potential loss of function; found in cancer samples. |
| c.1543C>T (p.Arg515Trp) | Missense | Rare (MAF 0.0002) | May disrupt protein-protein interaction; reported in bipolar disorder. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CRY2, such as frameshift or nonsense variants, lead to reduced repression of CLOCK/BMAL1, causing circadian disruption and increased cell proliferation. These are observed in cancers and metabolic disorders.
Gain of Function (GOF)
Gain-of-function mutations are rare but may enhance CRY2 stability or repressive activity, leading to altered circadian period and potential mood disorders. No specific variants have been confirmed as gain-of-function.
Dominant Negative (DN)
Dominant-negative mutations, such as p.Arg596Cys, can interfere with the formation of the CRY2-BMAL1 complex, impairing circadian regulation. This mechanism is implicated in DSPD.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding transcription factor activity | • Flavin adenine dinucleotide binding |
| • Protein homodimerization activity | • Circadian rhythm |
| • Negative regulation of transcription by RNA polymerase II | • Response to light stimulus |
| • Regulation of insulin secretion | • Cell cycle arrest |
Pathways
• Circadian Clock
• BMAL1/CLOCK regulation
• Melatonin metabolism
• Insulin signaling
• p53 signaling (via interaction with MDM2)
Protein Summary
The CRY2 protein is a 593-amino acid flavoprotein that contains a photolyase-like domain and a C-terminal regulatory domain. It functions as a transcriptional repressor within the circadian feedback loop: after heterodimerization with BMAL1, it translocates to the nucleus and inhibits CLOCK-BMAL1-mediated transcription. CRY2 also interacts with other proteins such as FBXL3 and MDM2, linking circadian regulation to protein degradation and DNA damage response. Its expression is ubiquitous but varies by tissue, with high levels in the brain and liver. Post-translational modifications, including phosphorylation and ubiquitination, regulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRY2 Knockout HEK293 Cell Line | EDJ-KQ4349 | Human | 1408 | Details Get a Quote |
| CRY2 Knockout HCT 116 Cell Line | EDJ-KQ25569 | Human | 1408 | Details Get a Quote |
| CRY2 Knockout A-549 Cell Line | EDJ-KQ26853 | Human | 1408 | Details Get a Quote |
| CRY2 Knockout HeLa Cell Line | EDJ-KQ26854 | Human | 1408 | Details Get a Quote |
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