In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
Transcription factors with Perturb-seq knockdown data for CHEK2. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = CHEK2 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of CHEK2, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr22:28,442,238–28,442,891 | 299.4 kb | Distal (>10kb) Multiome | 615 | |
| chr22:28,679,491–28,680,261 | 61.9 kb | Distal (>10kb) Multiome | 374 | |
| chr22:28,736,360–28,736,647 | 5.2 kb | Proximal (<10kb) | 92 | |
| chr22:28,741,336–28,742,751 | 104 bp | At TSS Multiome | 926 | |
| chr22:28,772,518–28,773,373 | 31.0 kb | Distal (>10kb) Multiome | 796 | |
| chr22:28,800,006–28,801,035 | 58.8 kb | Distal (>10kb) Multiome | 829 | |
| chr22:28,882,670–28,884,893 | 141.6 kb | Distal (>10kb) Multiome | 802 | |
| chr22:29,004,535–29,005,249 | 263.1 kb | Distal (>10kb) Multiome | 417 | |
| chr22:29,029,712–29,031,115 | 289.0 kb | Distal (>10kb) Multiome | 773 |
Genomic view of the CHEK2 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.