The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II), aspartate transcarbamoylase, and dihydroorotase. This protein is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of the MAPK cascade and de novo biosynthesis of pyrimidine nucleotides. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Transcription factors with Perturb-seq knockdown data for CAD. 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 = CAD 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 CAD, 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 |
|---|---|---|---|---|
| chr2:26,961,589–26,962,066 | 255.5 kb | Distal (>10kb) Multiome | 502 | |
| chr2:26,970,294–26,971,331 | 246.8 kb | Distal (>10kb) Multiome | 572 | |
| chr2:27,032,577–27,033,271 | 184.5 kb | Distal (>10kb) Multiome | 799 | |
| chr2:27,049,564–27,052,299 | 166.6 kb | Distal (>10kb) Multiome | 1295 | |
| chr2:27,071,223–27,072,896 | 145.6 kb | Distal (>10kb) Multiome | 864 | |
| chr2:27,081,006–27,081,641 | 136.1 kb | Distal (>10kb) Multiome | 758 | |
| chr2:27,085,591–27,087,452 | 130.8 kb | Distal (>10kb) Multiome | 970 | |
| chr2:27,123,498–27,124,089 | 93.6 kb | Distal (>10kb) Multiome | 553 | |
| chr2:27,133,917–27,135,216 | 82.7 kb | Distal (>10kb) Multiome | 815 | |
| chr2:27,211,255–27,212,840 | 5.3 kb | Proximal (<10kb) Multiome | 978 | |
| chr2:27,217,045–27,218,005 | 9 bp | At TSS Multiome | 771 | |
| chr2:27,250,040–27,250,883 | 33.0 kb | Distal (>10kb) Multiome | 559 | |
| chr2:27,262,260–27,263,337 | 45.5 kb | Distal (>10kb) Multiome | 376 | |
| chr2:27,264,406–27,265,326 | 47.7 kb | Distal (>10kb) Multiome | 696 | |
| chr2:27,306,488–27,307,261 | 89.2 kb | Distal (>10kb) Multiome | 115 | |
| chr2:27,322,773–27,323,423 | 105.7 kb | Distal (>10kb) Multiome | 906 | |
| chr2:27,356,094–27,357,596 | 139.5 kb | Distal (>10kb) Multiome | 1084 | |
| chr2:27,369,685–27,371,261 | 153.0 kb | Distal (>10kb) Multiome | 1096 | |
| chr2:27,380,026–27,381,202 | 163.4 kb | Distal (>10kb) Multiome | 821 | |
| chr2:27,408,972–27,410,056 | 192.3 kb | Distal (>10kb) Multiome | 989 | |
| chr2:27,428,202–27,429,633 | 211.3 kb | Distal (>10kb) Multiome | 1013 | |
| chr2:27,441,811–27,442,884 | 225.0 kb | Distal (>10kb) Multiome | 380 | |
| chr2:27,489,334–27,490,205 | 272.4 kb | Distal (>10kb) Multiome | 731 | |
| chr2:27,494,797–27,495,577 | 277.8 kb | Distal (>10kb) Multiome | 380 | |
| chr2:27,517,085–27,517,958 | 300.2 kb | Distal (>10kb) Multiome | 130 |
Genomic view of the CAD 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.