Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]
Transcription factors with Perturb-seq knockdown data for GSAP. 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 = GSAP 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 GSAP, 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 |
|---|---|---|---|---|
| chr7:77,121,873–77,122,882 | 293.9 kb | Distal (>10kb) Multiome | 516 | |
| chr7:77,415,516–77,416,893 | 132 bp | At TSS Multiome | 711 | |
| chr7:77,425,748–77,425,958 | 9.4 kb | Proximal (<10kb) | 164 | |
| chr7:77,536,195–77,538,947 | 120.7 kb | Distal (>10kb) Multiome | 1033 | |
| chr7:77,695,815–77,697,645 | 280.0 kb | Distal (>10kb) Multiome | 929 |
Genomic view of the GSAP 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.