PSEN2

Chr 1q42.13

presenilin 2

Aliases:: AD3L, STM2, PS2, PS-2, E5-1
MANE:: ENST00000366783.8

OMIM: 600759 ↗NCBI: 5664 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

PSEN2 · P49810

v62025-08-01

Predicted Aligned Error matrix for PSEN2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

71.8/ 100

Confident

448 residues

Confidence breakdown

Very high(≥ 90)38%
Confident(70–90)26%
Low(50–70)7%
Very low(< 50)29%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult onset neurodegenerative disorder
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dementia (encompassing fronto-temporal dementia and prion disease)
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dilated Cardiomyopathy and conduction defects
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

early-onset autosomal dominant Alzheimer disease
0.81
desmoid tumor
0.50
dilated cardiomyopathy 1V
0.50
familial isolated dilated cardiomyopathy
0.42
Alzheimer disease
0.42
neoplasm
0.40
dementia
0.39
diabetes mellitus
0.29
fibromatosis
0.28
Parkinson disease
0.27

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Presenilin-2

Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10497236, PubMed:10652302, PubMed:16752394, PubMed:27293189, PubMed:36272978). Selectively cleaves late endosomal/lysosomal localized substrates and generates the prominent pool of intracellular amyloid beta that contains longer amyloid beta (PubMed:27293189). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis (PubMed:16959576). Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria (PubMed:21285369)

Curated MONDO disease pages that list PSEN2 among their top associated genes.

early-onset autosomal dominant Alzheimer diseaseRare

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Disease associations (Open Targets)

Protein function (UniProt)

Diseases associated with PSEN2