NCSTN
nicastrin | APH2, KIAA0253

This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]

Biological processes 66 terms
ATPase binding (GO:0051117)Golgi apparatus (GO:0005794)Golgi apparatus (GO:0005794)Golgi membrane (GO:0000139)Notch receptor processing (GO:0007220)Notch receptor processing (GO:0007220)Notch receptor processing (GO:0007220)Notch receptor processing (GO:0007220)Notch receptor processing (GO:0007220)amyloid precursor protein catabolic process (GO:0042987)amyloid precursor protein catabolic process (GO:0042987)amyloid precursor protein catabolic process (GO:0042987)amyloid precursor protein metabolic process (GO:0042982)amyloid-beta formation (GO:0034205)amyloid-beta formation (GO:0034205)amyloid-beta formation (GO:0034205)aspartic endopeptidase activity, intramembrane cleaving (GO:0042500)azurophil granule membrane (GO:0035577)cerebellum development (GO:0021549)cytoplasmic vesicle membrane (GO:0030659)early endosome (GO:0005769)endomembrane system (GO:0012505)endopeptidase activator activity (GO:0061133)endopeptidase activator activity (GO:0061133)endopeptidase activity (GO:0004175)endoplasmic reticulum (GO:0005783)endoplasmic reticulum (GO:0005783)endoplasmic reticulum membrane (GO:0005789)endosome membrane (GO:0010008)extracellular exosome (GO:0070062)focal adhesion (GO:0005925)gamma-secretase complex (GO:0070765)gamma-secretase complex (GO:0070765)gamma-secretase complex (GO:0070765)gamma-secretase complex (GO:0070765)growth factor receptor binding (GO:0070851)lysosomal membrane (GO:0005765)lysosomal membrane (GO:0005765)lysosome (GO:0005764)melanosome (GO:0042470)membrane (GO:0016020)membrane (GO:0016020)membrane (GO:0016020)membrane (GO:0016020)membrane protein ectodomain proteolysis (GO:0006509)membrane protein intracellular domain proteolysis (GO:0031293)peptidase activity (GO:0008233)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)presynaptic membrane (GO:0042734)protein binding (GO:0005515)protein processing (GO:0016485)protein processing (GO:0016485)protein processing (GO:0016485)protein processing (GO:0016485)protein processing (GO:0016485)protein-containing complex (GO:0032991)protein-macromolecule adaptor activity (GO:0030674)protein-macromolecule adaptor activity (GO:0030674)proteolysis (GO:0006508)sarcolemma (GO:0042383)secretory vesicle (GO:0099503)synaptic membrane (GO:0097060)synaptic vesicle (GO:0008021)
Expression (TPM)
NCSTN — as a Regulated Gene

TFs regulating NCSTN 0 TFs

Transcription factors with Perturb-seq knockdown data for NCSTN. 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 = NCSTN upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to NCSTN

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of NCSTN, 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
chr1:160,046,290–160,047,082 296.7 kb Distal (>10kb) Multiome 540
chr1:160,069,829–160,071,049 272.9 kb Distal (>10kb) Multiome 419
chr1:160,083,809–160,084,575 259.2 kb Distal (>10kb) Multiome 327
chr1:160,095,707–160,096,231 247.4 kb Distal (>10kb) Multiome 79
chr1:160,097,214–160,099,572 244.5 kb Distal (>10kb) Multiome 659
chr1:160,100,845–160,101,543 242.2 kb Distal (>10kb) Multiome 530
chr1:160,169,049–160,170,141 173.7 kb Distal (>10kb) Multiome 330
chr1:160,192,913–160,193,769 150.1 kb Distal (>10kb) Multiome 551
chr1:160,204,860–160,206,035 137.9 kb Distal (>10kb) Multiome 637
chr1:160,261,515–160,263,143 80.9 kb Distal (>10kb) Multiome 992
chr1:160,284,609–160,285,332 58.2 kb Distal (>10kb) Multiome 638
chr1:160,342,945–160,343,700 70 bp At TSS Multiome 868
chr1:160,399,764–160,401,441 57.0 kb Distal (>10kb) Multiome 590
chr1:160,539,925–160,540,644 196.9 kb Distal (>10kb) Multiome 479
chr1:160,619,659–160,620,443 276.7 kb Distal (>10kb) Multiome 187

Genome Browser

Genomic view of the NCSTN 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.

chr1:160,036,290 – 160,630,443
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq