PSEN2 (Presenilin 2) Gene
Key regulator of gamma-secretase activity and early-onset Alzheimer disease
Gene Information Card
| Symbol | PSEN2 |
|---|---|
| Full Name | Presenilin 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q42.13 |
| NCBI Gene ID | 5664 ncbi.nlm.nih.gov/gene/5664 |
| Ensembl ID | ENSG00000143801 |
| UniProt ID | P49810 |
| OMIM ID | 600759 |
| HGNC ID | 9509 |
| Aliases | AD4, STM2, PS2, AD5, CMD1V |
Description
PSEN2 (presenilin 2) is a protein-coding gene that encodes a transmembrane protein, a catalytic subunit of the gamma-secretase complex. This complex cleaves integral membrane proteins such as Notch receptors and the amyloid-beta precursor protein (APP). Mutations in PSEN2 are a cause of early-onset familial Alzheimer disease (EOFAD) and are also associated with dilated cardiomyopathy (CMD1V).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease 4 (AD4) | Missense mutations alter gamma-secretase activity, increasing the Aβ42/Aβ40 ratio, promoting amyloid plaque formation. | ClinVar, OMIM |
| Dilated cardiomyopathy 1V (CMD1V) | Loss-of-function mutations impair Notch signaling during cardiac development, leading to dilated cardiomyopathy. | OMIM, PubMed |
| Frontotemporal dementia (FTD) | Rare variants in PSEN2 have been reported in FTD cases, possibly through altered APP processing. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Medium |
| Pancreas | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in Alzheimer studies |
| HEK293 (embryonic kidney) | 9.8 | Moderate expression; common for gamma-secretase assays |
| HepG2 (hepatocellular carcinoma) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asn141Ile (N141I) | Missense | Rare | Increases Aβ42/Aβ40 ratio; associated with early-onset AD |
| p.Met239Val (M239V) | Missense | Rare | Alters gamma-secretase cleavage; linked to AD |
| p.Thr122Pro (T122P) | Missense | Very rare | Reported in dilated cardiomyopathy; reduces gamma-secretase activity |
Mutation functional classification
Loss of Function (LOF)
Rare truncating and missense variants (e.g., T122P) reduce gamma-secretase activity, linked to dilated cardiomyopathy.
Gain of Function (GOF)
Common AD-associated missense mutations (e.g., N141I) increase Aβ42 production, considered a toxic gain of function.
Dominant Negative (DN)
Some PSEN2 mutants may interfere with wild-type presenilin function in the gamma-secretase complex, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • endopeptidase activity (GO:0004175) | • endoplasmic reticulum (GO:0005783) |
| • integral component of membrane (GO:0016021) | • Notch signaling pathway (GO:0007219) |
| • amyloid-beta formation (GO:0042987) |
Pathways
• Alzheimer disease (KEGG: hsa05010)
• Notch signaling pathway (KEGG: hsa04330)
• Gamma-secretase complex (Reactome: R-HSA-157906)
Protein Summary
Presenilin 2 (P49810) is a 448-amino acid multi-pass transmembrane protein that forms the catalytic core of the gamma-secretase complex. It undergoes endoproteolytic cleavage to generate N-terminal and C-terminal fragments that associate with nicastrin, APH1, and PEN2. PSEN2 is ubiquitously expressed, with highest levels in brain and heart. Its primary function is the intramembrane cleavage of type I transmembrane proteins, including APP and Notch. Mutations in PSEN2 are a major cause of early-onset familial Alzheimer disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSEN2 Knockout HEK293 Cell Line | EDJ-KQ443 | Human | 5664 | Details Get a Quote |
| PSEN2 Knockout A-549 Cell Line | EDJ-KQ18003 | Human | 5664 | Details Get a Quote |
| PSEN2 Knockout HCT 116 Cell Line | EDJ-KQ18745 | Human | 5664 | Details Get a Quote |
| PSEN2 Knockout HeLa Cell Line | EDJ-KQ18746 | Human | 5664 | Details Get a Quote |
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