Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [provided by RefSeq, Aug 2017]
Transcription factors with Perturb-seq knockdown data for TYMS. 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 = TYMS 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 TYMS, 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 |
|---|---|---|---|---|
| chr18:267,462–268,836 | 389.7 kb | Distal (>10kb) Multiome HiCAR | 1007 | |
| chr18:499,984–501,449 | 156.9 kb | Distal (>10kb) Multiome | 306 | |
| chr18:516,064–516,762 | 141.3 kb | Distal (>10kb) Multiome | 96 | |
| chr18:596,942–597,511 | 60.6 kb | Distal (>10kb) Multiome | 522 | |
| chr18:653,638–653,917 | 3.7 kb | Proximal (<10kb) | 21 | |
| chr18:657,152–658,975 | 742 bp | At TSS Multiome | 968 | |
| chr18:685,991–687,114 | 28.9 kb | Distal (>10kb) Multiome | 127 | |
| chr18:712,215–713,458 | 55.1 kb | Distal (>10kb) Multiome | 797 | |
| chr18:811,520–813,366 | 154.8 kb | Distal (>10kb) Multiome | 893 | |
| chr18:906,154–908,403 | 249.1 kb | Distal (>10kb) Multiome | 273 |
Genomic view of the TYMS 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.