This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]
Transcription factors with Perturb-seq knockdown data for GCH1. 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 = GCH1 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 GCH1, 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 |
|---|---|---|---|---|
| chr14:54,773,202–54,773,766 | 129.4 kb | Distal (>10kb) Multiome | 548 | |
| chr14:54,805,654–54,806,307 | 96.9 kb | Distal (>10kb) Multiome | 376 | |
| chr14:54,901,803–54,903,430 | 17 bp | At TSS Multiome | 886 | |
| chr14:54,912,511–54,912,707 | 9.7 kb | Proximal (<10kb) | 11 | |
| chr14:55,026,752–55,027,732 | 124.5 kb | Distal (>10kb) Multiome | 918 | |
| chr14:55,051,004–55,052,455 | 148.9 kb | Distal (>10kb) Multiome | 1079 | |
| chr14:55,103,022–55,103,627 | 200.5 kb | Distal (>10kb) Multiome | 700 | |
| chr14:55,128,954–55,130,369 | 226.5 kb | Distal (>10kb) Multiome | 569 | |
| chr14:55,191,089–55,192,110 | 288.9 kb | Distal (>10kb) Multiome | 702 |
Genomic view of the GCH1 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.