This gene encodes a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1 homolog B (APH1B), along with the presenilin, nicastrin, and presenilin enhancer-2 proteins. The precise function of this seven-transmembrane-domain protein is unknown though it is suspected of facilitating the association of nicastrin and presenilin in the gamma secretase complex as well as interacting with substrates of the gamma secretase complex prior to their proteolytic processing. Polymorphisms in a promoter region of this gene have been associated with an increased risk for developing sporadic Alzheimer's disease. Alternative splicing results in multiple protein-coding and non-protein-coding transcript variants. [provided by RefSeq, Aug 2011]
Transcription factors with Perturb-seq knockdown data for APH1A. 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 = APH1A 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 APH1A, 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 |
|---|---|---|---|---|
| chr1:150,010,143–150,011,088 | 258.3 kb | Distal (>10kb) Multiome | 961 | |
| chr1:150,066,903–150,067,886 | 201.4 kb | Distal (>10kb) Multiome | 986 | |
| chr1:150,149,493–150,150,439 | 118.9 kb | Distal (>10kb) Multiome | 448 | |
| chr1:150,162,838–150,163,636 | 105.7 kb | Distal (>10kb) Multiome | 550 | |
| chr1:150,213,532–150,214,095 | 55.3 kb | Distal (>10kb) Multiome | 441 | |
| chr1:150,234,435–150,235,519 | 34.3 kb | Distal (>10kb) Multiome | 725 | |
| chr1:150,235,635–150,236,696 | 32.8 kb | Distal (>10kb) Multiome | 905 | |
| chr1:150,255,443–150,256,199 | 13.3 kb | Distal (>10kb) Multiome | 441 | |
| chr1:150,256,563–150,257,324 | 12.0 kb | Distal (>10kb) Multiome | 223 | |
| chr1:150,257,589–150,258,594 | 10.9 kb | Distal (>10kb) Multiome | 233 | |
| chr1:150,259,728–150,260,778 | 8.9 kb | Proximal (<10kb) Multiome | 362 | |
| chr1:150,268,574–150,269,453 | 83 bp | At TSS Multiome | 785 | |
| chr1:150,272,599–150,272,771 | 3.6 kb | Proximal (<10kb) | 122 | |
| chr1:150,281,629–150,283,038 | 13.4 kb | Distal (>10kb) Multiome | 503 | |
| chr1:150,293,680–150,294,144 | 24.8 kb | Distal (>10kb) Multiome | 755 | |
| chr1:150,313,761–150,314,506 | 45.1 kb | Distal (>10kb) Multiome | 108 | |
| chr1:150,321,137–150,321,825 | 52.5 kb | Distal (>10kb) Multiome | 806 | |
| chr1:150,363,368–150,364,980 | 95.0 kb | Distal (>10kb) Multiome | 971 | |
| chr1:150,487,154–150,487,710 | 218.3 kb | Distal (>10kb) Multiome | 929 | |
| chr1:150,515,085–150,516,227 | 246.6 kb | Distal (>10kb) Multiome | 781 | |
| chr1:150,548,849–150,549,823 | 280.2 kb | Distal (>10kb) Multiome | 620 | |
| chr1:150,560,828–150,562,623 | 292.3 kb | Distal (>10kb) Multiome | 897 |
Genomic view of the APH1A 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.