This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
Transcription factors with Perturb-seq knockdown data for NPC1. 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 = NPC1 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 NPC1, 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 |
|---|---|---|---|---|
| chr18:23,437,346–23,438,074 | 148.6 kb | Distal (>10kb) Multiome | 628 | |
| chr18:23,452,793–23,453,775 | 133.3 kb | Distal (>10kb) Multiome | 796 | |
| chr18:23,502,975–23,503,998 | 83.1 kb | Distal (>10kb) Multiome | 907 | |
| chr18:23,586,020–23,587,174 | 239 bp | At TSS Multiome | 908 | |
| chr18:23,609,370–23,609,991 | 23.2 kb | Distal (>10kb) Multiome | 79 | |
| chr18:23,618,918–23,619,643 | 32.8 kb | Distal (>10kb) Multiome | 295 | |
| chr18:23,662,307–23,663,058 | 76.3 kb | Distal (>10kb) Multiome | 349 | |
| chr18:23,689,205–23,690,311 | 103.0 kb | Distal (>10kb) Multiome | 469 | |
| chr18:23,721,611–23,722,408 | 135.6 kb | Distal (>10kb) Multiome | 82 |
Genomic view of the NPC1 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.