GSAP (Gamma-Secretase Activating Protein)
A key regulator of gamma-secretase activity, implicated in Alzheimer's disease and cancer.
Gene Information Card
| Symbol | GSAP |
|---|---|
| Full Name | Gamma-Secretase Activating Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 100288332 ncbi.nlm.nih.gov/gene/100288332 |
| Ensembl ID | ENSG00000204619 |
| UniProt ID | A8MPY1 |
| OMIM ID | 615718 |
| HGNC ID | HGNC:37228 |
| Aliases | PION, GASP, MGC138290 |
Description
GSAP (Gamma-Secretase Activating Protein) is a protein-coding gene that encodes a protein which selectively activates gamma-secretase to cleave the amyloid precursor protein (APP), producing amyloid-beta peptides. It is involved in the pathogenesis of Alzheimer's disease and has been implicated in various cancers through its role in Notch signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's Disease | GSAP enhances gamma-secretase cleavage of APP, increasing amyloid-beta production, a hallmark of Alzheimer's pathology. | PMID: 20037584; NCBI Gene |
| Cancer (various) | GSAP modulates Notch signaling via gamma-secretase, influencing cell proliferation and differentiation in tumors. | PMID: 23431136; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Low |
| Lung | 6.1 | Low |
| Liver | 3.4 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate expression |
| HeLa (cervical cancer) | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Unknown effect on gamma-secretase activity |
| c.205G>A (p.Gly69Arg) | Missense | <0.01% | Potential loss of function |
| c.340_341insA | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations likely reduce GSAP protein levels or activity, impairing gamma-secretase activation.
Gain of Function (GOF)
Missense mutations may enhance GSAP binding to gamma-secretase, increasing amyloid-beta production.
Dominant Negative (DN)
Not reported for GSAP.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • protein processing (GO:0016485) |
| • amyloid-beta formation (GO:0042987) | • positive regulation of Notch signaling pathway (GO:0007221) |
Pathways
• Alzheimer's disease - amyloidogenic pathway
• Notch signaling pathway
Protein Summary
The GSAP protein is a 98-amino acid intracellular protein that interacts with the gamma-secretase complex and the amyloid precursor protein (APP) to selectively promote APP cleavage over Notch. It is primarily expressed in the brain and testis, and its dysregulation is linked to Alzheimer's disease and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSAP Knockout HEK293 Cell Line | EDJ-KQ11387 | Human | 54103 | Details Get a Quote |
| GSAP Knockout A-549 Cell Line | EDJ-KQ39593 | Human | 54103 | Details Get a Quote |
| GSAP Knockout HeLa Cell Line | EDJ-KQ56396 | Human | 54103 | Details Get a Quote |
| GSAP Knockout HCT 116 Cell Line | EDJ-KQ73332 | Human | 54103 | Details Get a Quote |
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