CLOCK
Circadian Locomotor Output Cycles Kaput
Gene Information Card
| Symbol | CLOCK |
|---|---|
| Full Name | Circadian Locomotor Output Cycles Kaput |
| Gene Type | Protein coding |
| Chromosomal Location | 4q12 |
| NCBI Gene ID | 9575 ncbi.nlm.nih.gov/gene/9575 |
| Ensembl ID | ENSG00000134852 |
| UniProt ID | O15516 |
| OMIM ID | 601851 |
| HGNC ID | 2082 |
| Aliases | bHLHe8, KAT13D, KIAA0334 |
Description
The CLOCK gene encodes a basic helix-loop-helix (bHLH) transcription factor that is a core component of the circadian clock. It forms a heterodimer with ARNTL (BMAL1) to activate transcription of downstream clock genes (e.g., PER, CRY) and regulates numerous physiological processes including sleep-wake cycles, metabolism, and cell proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sleep disorders (e.g., familial advanced sleep phase syndrome) | CLOCK variants alter circadian period length and phase | OMIM 601851; ClinVar |
| Metabolic syndrome | CLOCK dysregulation disrupts glucose and lipid metabolism | NCBI Gene; PubMed |
| Cancer (e.g., breast, colorectal) | CLOCK overexpression or mutation affects cell cycle and DNA repair | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 15.2 | Medium |
| Liver | 8.5 | Low |
| Heart | 6.3 | Low |
| Testis | 12.1 | Medium |
| Pancreas | 7.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | Embryonic kidney |
| HeLa | 14.7 | Cervical carcinoma |
| HepG2 | 9.2 | Hepatocellular carcinoma |
| MCF7 | 11.5 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.157G>A (p.Gly53Arg) | Missense | <0.01% | Altered dimerization with BMAL1 |
| c.1060C>T (p.Arg354Trp) | Missense | <0.01% | Reduced transcriptional activity |
| c.1978_1980del (p.Lys660del) | In-frame deletion | <0.01% | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg354Trp) reduce transactivation of clock target genes.
Gain of Function (GOF)
Not well documented; some variants may increase transcriptional activity.
Dominant Negative (DN)
p.Gly53Arg may interfere with wild-type CLOCK-BMAL1 complex formation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Circadian rhythm (KEGG: hsa04710)
• Circadian entrainment (KEGG: hsa04713)
• Transcriptional regulation by CLOCK-ARNTL (Reactome: R-HSA-1368082)
Protein Summary
CLOCK is a 846-amino acid protein containing a bHLH domain and a PAS domain, essential for dimerization with BMAL1 and DNA binding. It also possesses intrinsic histone acetyltransferase (HAT) activity, contributing to chromatin remodeling. The protein is ubiquitously expressed and regulates circadian rhythms, metabolism, and cell cycle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLOCK Knockout HEK293 Cell Line | EDJ-KQ990 | Human | 9575 | Details Get a Quote |
| CLOCK Knockout A-549 Cell Line | EDJ-KQ20018 | Human | 9575 | Details Get a Quote |
| CLOCK Knockout HCT 116 Cell Line | EDJ-KQ20019 | Human | 9575 | Details Get a Quote |
| CLOCK Knockout HeLa Cell Line | EDJ-KQ20020 | Human | 9575 | Details Get a Quote |
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