NCSTN Gene: Nicastrin
A key component of the gamma-secretase complex involved in Notch signaling and Alzheimer disease
Gene Information Card
| Symbol | NCSTN |
|---|---|
| Full Name | Nicastrin |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.2 |
| NCBI Gene ID | 23385 ncbi.nlm.nih.gov/gene/23385 |
| Ensembl ID | ENSG00000162736 |
| UniProt ID | Q92542 |
| OMIM ID | 605254 |
| HGNC ID | 17091 |
| Aliases | KIAA0253, ATAG1874, RP11-517B11.2 |
Description
NCSTN encodes nicastrin, a type I transmembrane glycoprotein that is an essential component of the gamma-secretase complex. This complex mediates intramembrane proteolysis of substrates such as Notch receptors and amyloid precursor protein (APP). Nicastrin stabilizes the complex and is required for substrate recognition. Mutations in NCSTN are associated with familial hidradenitis suppurativa (acne inversa) and have been implicated in Alzheimer disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hidradenitis suppurativa, familial (acne inversa) | Loss-of-function mutations in NCSTN impair gamma-secretase activity, leading to altered Notch signaling in skin follicles. | OMIM #613737; ClinVar |
| Alzheimer disease | Altered gamma-secretase processing of APP may increase amyloid-beta production; rare variants may modify risk. | OMIM #104300; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 9.5 | Low |
| Kidney | 11.3 | Medium |
| Skin | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.5 | Embryonic kidney cells |
| SH-SY5Y | 16.2 | Neuroblastoma cells |
| HeLa | 13.8 | Cervical carcinoma cells |
| HepG2 | 10.9 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.349C>T (p.Arg117*) | Nonsense | Rare | Loss of function; associated with hidradenitis suppurativa |
| c.1105C>T (p.Arg369*) | Nonsense | Rare | Loss of function; associated with hidradenitis suppurativa |
| c.1759C>T (p.Arg587Trp) | Missense | Rare | Unknown; reported in Alzheimer disease cohorts |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg117*, p.Arg369*) cause premature truncation, reducing gamma-secretase activity and impairing Notch signaling, leading to hidradenitis suppurativa.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in NCSTN.
Dominant Negative (DN)
Haploinsufficiency is the proposed mechanism for hidradenitis suppurativa; dominant-negative effects have not been established.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • plasma membrane (GO:0005886) |
| • integral component of membrane (GO:0016021) | • endopeptidase activity (GO:0004175) |
| • integrin-mediated signaling pathway (GO:0007229) | • Notch signaling pathway (GO:0007219) |
| • gamma-secretase complex (GO:0031293) |
Pathways
• Notch signaling pathway (KEGG hsa04330)
• Alzheimer disease (KEGG hsa05010)
• Presenilin-mediated gamma-secretase pathway (Reactome R-HSA-9013508)
Protein Summary
Nicastrin is a 709-amino-acid type I transmembrane glycoprotein that serves as a scaffold and substrate receptor for the gamma-secretase complex. It contains a large extracellular domain with a peptidase-like fold that is critical for substrate binding. Nicastrin is essential for the maturation and stability of the gamma-secretase complex, which cleaves multiple transmembrane proteins including Notch receptors and APP. Mutations in NCSTN cause familial hidradenitis suppurativa due to impaired Notch signaling in skin.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCSTN Knockout HEK293 Cell Line | EDJ-KQ434 | Human | 23385 | Details Get a Quote |
| NCSTN Knockout HeLa Cell Line | EDJ-KQ18314 | Human | 23385 | Details Get a Quote |
| NCSTN Knockout A-549 Cell Line | EDJ-KQ18730 | Human | 23385 | Details Get a Quote |
| NCSTN Knockout HCT 116 Cell Line | EDJ-KQ18731 | Human | 23385 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
