PER2 Gene - Period Circadian Regulator 2
Key regulator of the mammalian circadian clock, implicated in sleep disorders and cancer susceptibility.
Gene Information Card
| Symbol | PER2 |
|---|---|
| Full Name | Period Circadian Regulator 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 8864 ncbi.nlm.nih.gov/gene/8864 |
| Ensembl ID | ENSG00000132326 |
| UniProt ID | O15055 |
| OMIM ID | 603426 |
| HGNC ID | 8846 |
| Aliases | FASPS, FASPS1, KIAA0335, MGC111083, MGC111084, MGC111085 |
Description
The PER2 gene encodes a core component of the mammalian circadian clock. The PER2 protein forms a heterodimer with CRY proteins, which represses CLOCK/BMAL1-mediated transcription, generating a negative feedback loop that drives ~24-hour rhythms in behavior and physiology. Mutations in PER2 are associated with familial advanced sleep phase syndrome (FASPS) and altered cancer risk.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial Advanced Sleep Phase Syndrome (FASPS) | Missense mutations (e.g., S662G) alter PER2 phosphorylation and stability, shortening the circadian period. | OMIM #604348; PMID: 11533001 |
| Breast Cancer | PER2 downregulation disrupts circadian control of cell cycle and DNA repair, promoting tumorigenesis. | PMID: 20053714; COSMIC |
| Colorectal Cancer | PER2 promoter hypermethylation and reduced expression correlate with poor prognosis. | PMID: 20628086; COSMIC |
| Non-Hodgkin Lymphoma | PER2 polymorphisms (e.g., rs2304672) associated with increased risk. | PMID: 17989333 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 10.8 | Medium |
| Heart | 6.2 | Low |
| Liver | 4.1 | Low |
| Pancreas | 3.5 | Low |
| Testis | 8.9 | Medium |
| Skeletal muscle | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 11.4 | Medium expression |
| MCF7 | 8.7 | Medium expression |
| HepG2 | 5.3 | Low expression |
| A549 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1984A>G (p.Ser662Gly) | Missense | <0.01% | Shortens circadian period; causes FASPS |
| c.2101C>T (p.Arg701Trp) | Missense | <0.01% | Alters PER2 stability; associated with FASPS |
| c.1249G>A (p.Gly417Arg) | Missense | <0.01% | Unknown functional effect; reported in ClinVar |
| c.1390_1391insA (p.Thr464Asnfs*12) | Frameshift | <0.01% | Loss of function; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr464Asnfs*12) lead to truncated protein and loss of repressor activity.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance repressor activity but evidence is limited.
Dominant Negative (DN)
The S662G mutation acts as a dominant-negative by disrupting PER2 phosphorylation and nuclear translocation, shortening the circadian period.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Circadian rhythm (KEGG: hsa04710)
• Circadian entrainment (KEGG: hsa04713)
• CLOCK/BMAL1-mediated transcription (Reactome: R-HSA-1368082)
• RORA/RORB/RORC regulation of circadian clock (Reactome: R-HSA-1368082)
Protein Summary
PER2 (Period Circadian Regulator 2) is a 1255-amino acid protein (UniProt O15055) that localizes to the nucleus and cytoplasm. It contains a PAS domain (residues 170-220) and a C-terminal nuclear export signal. PER2 heterodimerizes with CRY1/CRY2 and interacts with CLOCK/BMAL1 to repress transcription. Post-translational modifications (phosphorylation by CK1ε/δ, ubiquitination) regulate its stability and nuclear translocation. PER2 also modulates cell cycle checkpoints and DNA damage response independently of its circadian role.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PER2 Knockout HEK293 Cell Line | EDJ-KQ2265 | Human | 8864 | Details Get a Quote |
| CATSPER2 Knockout HEK293 Cell Line | EDJ-KQ6933 | Human | 117155 | Details Get a Quote |
| CATSPER2 Knockout HCT 116 Cell Line | EDJ-KQ32935 | Human | 117155 | Details Get a Quote |
| CATSPER2 Knockout HeLa Cell Line | EDJ-KQ32936 | Human | 117155 | Details Get a Quote |
| PER2 Knockout HeLa Cell Line | EDJ-KQ21277 | Human | 8864 | Details Get a Quote |
| PER2 Knockout A-549 Cell Line | EDJ-KQ22598 | Human | 8864 | Details Get a Quote |
| PER2 Knockout HCT 116 Cell Line | EDJ-KQ22599 | Human | 8864 | Details Get a Quote |
| CATSPER2 Knockout A-549 Cell Line | EDJ-KQ66491 | Human | 117155 | Details Get a Quote |
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