PSEN1 | ENSG00000080815 | NCBI 5663

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Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

Description
Proteins

## Summary Analyzed for its expression specificity (CSI Z-Score), presenilin 1 ([PSEN1](/details-gene/5663)) is characterized as a ubiquitously expressed gene essential for fundamental cellular processes rather than a defining marker for any specific cell type. Its broad expression landscape is consistent with its role as the catalytic subunit of the gamma-secretase complex, which is critical for intramembrane proteolysis of key substrates like Notch and the amyloid precursor protein. Mutations in [PSEN1](/details-gene/5663) are the most common cause of early-onset, autosomal dominant Alzheimer's disease ([OMIM: 104311](https://omim.org/entry/104311)), highlighting its central role in neurobiology and disease. ## Cellular Roles and Expression Landscape The expression profile of [PSEN1](/details-gene/5663), when evaluated for cell-type specificity, indicates a broad and constitutive pattern of expression across diverse lineages. In the **Overall** context, the CSI (Z-SCORE) is consistently `0.00` with non-significant p-values for all top-expressing cells, suggesting that its transcript levels do not uniquely distinguish any single cell population. Despite not being a specific marker, [PSEN1](/details-gene/5663) is expressed in a wide variety of cells, including those of the central nervous system like [oligodendrocyte](/details-cell/CL0000128) and [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064), as well as various immune cells such as [intermediate monocyte](/details-cell/CL0002393), [effector memory CD8-positive, alpha-beta T cell](/details-cell/CL0000913), and [alveolar macrophage](/details-cell/CL0000583). This ubiquitous expression pattern underscores its role in fundamental biological functions that are shared across different tissues and systems, rather than a specialized function confined to a particular cell type. This is consistent with its established role as a core component of the gamma-secretase complex, an essential cellular protease. ## Pathways and Molecular Function The broad expression of [PSEN1](/details-gene/5663) is reflected in its extensive involvement in numerous fundamental biological pathways. As the catalytic core of the gamma-secretase complex, its primary molecular function is [Aspartic endopeptidase activity, intramembrane cleaving](/details-go/GO:0042500), a process essential for the cleavage of Type I transmembrane proteins. This activity is critical for multiple signaling cascades, most notably the [Notch signaling pathway](/details-go/GO:0007219) ([R-HSA-157118](https://reactome.org/content/detail/R-HSA-157118)), which is indispensable for cell fate decisions during [Nervous system development](/details-pathway/R-HSA-9675108) and immune cell differentiation. Its best-known function is in the [Amyloid precursor protein metabolic process](/details-go/GO:0042982), where it mediates the final proteolytic cleavage that generates amyloid-beta peptides, a key event in the pathogenesis of Alzheimer's disease. Publications by Sherrington et al. (1995) first linked mutations in this gene to early-onset familial Alzheimer's disease ([PubMed: 7596406](https://pubmed.ncbi.nlm.nih.gov/7596406)). Beyond its role in proteolysis, [PSEN1](/details-gene/5663) is also implicated in [Calcium ion homeostasis](/details-go/GO:0055074), particularly within the endoplasmic reticulum, and plays roles in [Cell-cell adhesion](/details-go/GO:0098609) through its interaction with beta-catenin, as reported by Zhong et al. (1998) ([PubMed: 9738936](https://pubmed.ncbi.nlm.nih.gov/9738936)). This pleiotropy explains its necessity across the diverse cell types in which it is expressed. ## Research Directions The ubiquitous expression of [PSEN1](/details-gene/5663) complicates its study but also suggests that its function may be subtly modulated in a cell-type-specific manner, which could explain the neuron-centric pathology of Alzheimer's disease despite its widespread expression. ### Testable Hypotheses 1. **Cell-Specific Gamma-Secretase Interactomes Dictate Substrate Preference:** The ubiquitous expression of [PSEN1](/details-gene/5663) suggests that its pathogenic effects in specific neurons are not due to expression levels alone. It is hypothesized that the protein interaction network of the gamma-secretase complex varies between cell types, such as [oligodendrocyte](/details-cell/CL0000128) and [effector memory CD8-positive, alpha-beta T cell](/details-cell/CL0000913), leading to differential substrate preference and processing efficiency. * **Experimental Approach:** Employ proximity-dependent biotinylation (e.g., TurboID) fused to [PSEN1](/details-gene/5663) in iPSC-derived human neurons versus primary T cells. Subsequent mass spectrometry will identify differential interactors that could be validated for their ability to modulate Notch versus APP processing in vitro. 2. **Pathogenic PSEN1 Mutations Impair Immune Function via Dysregulated Notch Signaling:** The expression of [PSEN1](/details-gene/5663) in immune cells like [intermediate monocyte](/details-cell/CL0002393) implies a role in immune regulation. It is hypothesized that familial Alzheimer's disease-causing mutations in [PSEN1](/details-gene/5663) subtly impair Notch-dependent differentiation and activation in myeloid and lymphoid lineages, contributing to the neuroinflammatory environment seen in Alzheimer's disease. * **Experimental Approach:** Use CRISPR-Cas9 to introduce pathogenic [PSEN1](/details-gene/5663) mutations (e.g., A246E, L166P) into human hematopoietic stem cells. Differentiate these cells into monocytes and T cells and assess their functional responses (e.g., phagocytosis, cytokine release, T cell activation) and Notch signaling pathway integrity (e.g., HES/HEY family gene expression) upon stimulation. 3. **Differential Reliance on PSEN1-Mediated Calcium Leak Renders Neuronal Subtypes Vulnerable:** [PSEN1](/details-gene/5663) is involved in [Endoplasmic reticulum calcium ion homeostasis](/details-go/GO:0032469). It is hypothesized that distinct neuronal populations, such as [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) versus other cortical neurons, have different baseline dependencies on PSEN1 for ER calcium leak, making some subtypes exquisitely vulnerable to the calcium dysregulation caused by pathogenic mutations. * **Experimental Approach:** Generate iPSC-derived cortical interneurons and excitatory neurons harboring Alzheimer's-linked [PSEN1](/details-gene/5663) mutations. Use live-cell imaging with genetically encoded calcium indicators (e.g., GCaMP) targeted to the ER and cytosol to quantify resting calcium levels and store-operated calcium entry, revealing subtype-specific defects. ### Therapeutic Potential Targeting [PSEN1](/details-gene/5663) is challenging due to its vital role in Notch signaling, where complete inhibition can lead to severe toxicity. Therefore, therapeutic strategies have shifted from broad-spectrum gamma-secretase inhibitors to more nuanced gamma-secretase modulators (GSMs). These small molecules are designed to allosterically modify the enzyme complex to favor the production of shorter, less aggregation-prone amyloid-beta peptides without blocking the cleavage of other essential substrates like Notch. This approach holds promise for treating Alzheimer's disease by mitigating the primary pathogenic cascade while preserving essential cellular functions.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.

Presenilin-1
A0A0S2Z4D2_HUMAN

Genular Protein ID: 86159603

Symbol: PSN1_HUMAN

Name: Presenilin-1

UniProtKB Accession Codes:

P49768 B2R6D3 O95465 Q14762 Q15719 Q15720 Q96P33 Q9UIF0

Database IDs:

Citations:

PubMed ID: 7596406

Title: Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

PubMed ID: 7596406

DOI: 10.1038/375754a0

PubMed ID: 8641442

Title: Identification and characterization of presenilin I-467, I-463 and I-374.

PubMed ID: 8641442

DOI: 10.1016/0014-5793(96)00054-3

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9070286

Title: Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential expression in oogenesis and embryogenesis.

PubMed ID: 9070286

DOI: 10.1006/bbrc.1996.6043

PubMed ID: 8804415

Title: Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. Identification of a novel splice variant.

PubMed ID: 8804415

DOI: 10.1016/0014-5793(96)00845-9

PubMed ID: 15274632

Title: Purification and characterization of the human gamma-secretase complex.

PubMed ID: 15274632

DOI: 10.1021/bi0494976

PubMed ID: 8574969

Title: Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells.

PubMed ID: 8574969

DOI: 10.1038/nm0296-224

PubMed ID: 9173929

Title: Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue.

PubMed ID: 9173929

DOI: 10.1006/nbdi.1997.0129

PubMed ID: 9144240

Title: Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C.

PubMed ID: 9144240

DOI: 10.1073/pnas.94.10.5349

PubMed ID: 9485372

Title: Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa C-terminal fragment are death substrates for proteases of the caspase family.

PubMed ID: 9485372

DOI: 10.1021/bi972106l

PubMed ID: 9738936

Title: Direct association of presenilin-1 with beta-catenin.

PubMed ID: 9738936

DOI: 10.1016/s0014-5793(98)00886-2

PubMed ID: 9437013

Title: Interaction of presenilins with the filamin family of actin-binding proteins.

PubMed ID: 9437013

DOI: 10.1523/jneurosci.18-03-00914.1998

PubMed ID: 10545183

Title: Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis.

PubMed ID: 10545183

DOI: 10.1021/bi9914210

PubMed ID: 10551805

Title: Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1.

PubMed ID: 10551805

DOI: 10.1074/jbc.274.46.32543

PubMed ID: 10593990

Title: Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch.

PubMed ID: 10593990

DOI: 10.1074/jbc.274.51.36801

PubMed ID: 10037471

Title: Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin.

PubMed ID: 10037471

DOI: 10.1046/j.1471-4159.1999.0720999.x

PubMed ID: 10206644

Title: Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity.

PubMed ID: 10206644

DOI: 10.1038/19077

PubMed ID: 10899933

Title: Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling.

PubMed ID: 10899933

DOI: 10.1046/j.1471-4159.2000.0750583.x

PubMed ID: 10811883

Title: Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch.

PubMed ID: 10811883

DOI: 10.1073/pnas.100049897

PubMed ID: 11987239

Title: Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules.

PubMed ID: 11987239

DOI: 10.1006/bcmd.2002.0486

PubMed ID: 11953314

Title: A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions.

PubMed ID: 11953314

DOI: 10.1093/emboj/21.8.1948

PubMed ID: 11799129

Title: Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein.

PubMed ID: 11799129

DOI: 10.1074/jbc.m112372200

PubMed ID: 12058025

Title: A new splice variant of glial fibrillary acidic protein GFAPepsilon, interacts with the presenilin proteins.

PubMed ID: 12058025

DOI: 10.1074/jbc.m112121200

PubMed ID: 14515347

Title: Presenilin 1 is involved in maturation and trafficking of N-cadherin to the plasma membrane.

PubMed ID: 14515347

DOI: 10.1002/jnr.10753

PubMed ID: 12679784

Title: Reconstitution of gamma-secretase activity.

PubMed ID: 12679784

DOI: 10.1038/ncb960

PubMed ID: 12740439

Title: Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2.

PubMed ID: 12740439

DOI: 10.1073/pnas.1037392100

PubMed ID: 14759258

Title: An unappreciated role for RNA surveillance.

PubMed ID: 14759258

DOI: 10.1186/gb-2004-5-2-r8

PubMed ID: 15004326

Title: A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations.

PubMed ID: 15004326

DOI: 10.3233/jad-2004-6105

PubMed ID: 14576165

Title: Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis.

PubMed ID: 14576165

DOI: 10.1074/jbc.m306653200

PubMed ID: 15385547

Title: Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins.

PubMed ID: 15385547

DOI: 10.1074/jbc.m407898200

PubMed ID: 15341515

Title: Conserved residues within the putative active site of gamma-secretase differentially influence enzyme activity and inhibitor binding.

PubMed ID: 15341515

DOI: 10.1111/j.1471-4159.2004.02596.x

PubMed ID: 16126725

Title: Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability.

PubMed ID: 16126725

DOI: 10.1074/jbc.m507503200

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 16959576

Title: Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations.

PubMed ID: 16959576

DOI: 10.1016/j.cell.2006.06.059

PubMed ID: 16305624

Title: C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation.

PubMed ID: 16305624

DOI: 10.1111/j.1471-4159.2005.03548.x

PubMed ID: 8875251

Title: The presenilin genes: a new gene family involved in Alzheimer disease pathology.

PubMed ID: 8875251

DOI: 10.1093/hmg/5.supplement_1.1449

PubMed ID: 9521418

Title: Presenilin mutations in Alzheimer's disease.

PubMed ID: 9521418

DOI: 10.1002/(sici)1098-1004(1998)11:3<183::aid-humu1>3.0.co;2-j

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20299451

Title: Human CRB2 inhibits gamma-secretase cleavage of amyloid precursor protein by binding to the presenilin complex.

PubMed ID: 20299451

DOI: 10.1074/jbc.m109.038760

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 20929727

Title: Gamma-secretase gene mutations in familial acne inversa.

PubMed ID: 20929727

DOI: 10.1126/science.1196284

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 21143716

Title: Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation.

PubMed ID: 21143716

DOI: 10.1111/j.1600-0854.2010.01149.x

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 25394380

Title: G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation.

PubMed ID: 25394380

DOI: 10.1007/s12035-014-8969-1

PubMed ID: 25043039

Title: Three-dimensional structure of human gamma-secretase.

PubMed ID: 25043039

DOI: 10.1038/nature13567

PubMed ID: 26623517

Title: Sampling the conformational space of the catalytic subunit of human gamma-secretase.

PubMed ID: 26623517

DOI: 10.7554/elife.11182

PubMed ID: 26280335

Title: An atomic structure of human gamma-secretase.

PubMed ID: 26280335

DOI: 10.1038/nature14892

PubMed ID: 25918421

Title: Structural basis of human gamma-secretase assembly.

PubMed ID: 25918421

DOI: 10.1073/pnas.1506242112

PubMed ID: 30598546

Title: Structural basis of Notch recognition by human gamma-secretase.

PubMed ID: 30598546

DOI: 10.1038/s41586-018-0813-8

PubMed ID: 30630874

Title: Recognition of the amyloid precursor protein by human gamma-secretase.

PubMed ID: 30630874

DOI: 10.1126/science.aaw0930

PubMed ID: 8634711

Title: Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3.

PubMed ID: 8634711

DOI: 10.1093/hmg/4.12.2363

PubMed ID: 8634712

Title: Mutations of the presenilin I gene in families with early-onset Alzheimer's disease.

PubMed ID: 8634712

DOI: 10.1093/hmg/4.12.2373

PubMed ID: 7651536

Title: Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene.

PubMed ID: 7651536

DOI: 10.1038/376775a0

PubMed ID: 7550356

Title: The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families.

PubMed ID: 7550356

DOI: 10.1038/ng1095-219

PubMed ID: 8837617

Title: The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 deposition and severe cerebellar pathology.

PubMed ID: 8837617

DOI: 10.1038/nm1096-1146

PubMed ID: 8733303

Title: Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families.

PubMed ID: 8733303

DOI: 10.1016/0304-3940(96)12587-8

PubMed ID: 9225696

Title: Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation.

PubMed ID: 9225696

DOI: 10.1002/ana.410420121

PubMed ID: 9298817

Title: E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles.

PubMed ID: 9298817

DOI: 10.1002/(sici)1098-1004(1997)10:3<186::aid-humu2>3.0.co;2-h

PubMed ID: 9172170

Title: Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype.

PubMed ID: 9172170

DOI: 10.1097/00001756-199704140-00043

PubMed ID: 9833068

Title: A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer disease.

PubMed ID: 9833068

PubMed ID: 9851443

Title: The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease.

PubMed ID: 9851443

DOI: 10.1002/ana.410440617

PubMed ID: 9851450

Title: Missense mutation E318G of the presenilin-1 gene appears to be a nonpathogenic polymorphism.

PubMed ID: 9851450

DOI: 10.1002/ana.410440624

PubMed ID: 9384602

Title: Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease.

PubMed ID: 9384602

DOI: 10.1093/hmg/7.1.43

PubMed ID: 9521423

Title: Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene.

PubMed ID: 9521423

DOI: 10.1002/(sici)1098-1004(1998)11:3<216::aid-humu6>3.0.co;2-f

PubMed ID: 10200054

Title: Missense mutation in exon 11 (codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer's disease and transmission study by mismatch enhanced allele specific amplification.

PubMed ID: 10200054

DOI: 10.1002/(sici)1098-1004(1998)11:6<481::aid-humu12>3.0.co;2-q

PubMed ID: 9719376

Title: De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer's disease cases.

PubMed ID: 9719376

DOI: 10.1136/jmg.35.8.672

PubMed ID: 9507958

Title: A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years.

PubMed ID: 9507958

DOI: 10.1097/00001756-199801260-00008

PubMed ID: 9831473

Title: Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease.

PubMed ID: 9831473

DOI: 10.1097/00001756-199810050-00034

PubMed ID: 9915968

Title: The Glu318Gly substitution in presenilin 1 is not causally related to Alzheimer disease.

PubMed ID: 9915968

DOI: 10.1086/302200

PubMed ID: 10441572

Title: Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum.

PubMed ID: 10441572

DOI: 10.1086/302553

PubMed ID: 10090481

Title: Pathogenic presenilin 1 mutations (P436S and I143F) in early-onset Alzheimer's disease in the UK.

PubMed ID: 10090481

DOI: 10.1002/(sici)1098-1004(1999)13:3<256::aid-humu11>3.0.co;2-p

PubMed ID: 10447269

Title: A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease.

PubMed ID: 10447269

DOI: 10.1002/(sici)1098-1004(1999)14:1<90::aid-humu19>3.0.co;2-s

PubMed ID: 10533070

Title: DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations.

PubMed ID: 10533070

DOI: 10.1002/(sici)1098-1004(199911)14:5<433::aid-humu10>3.0.co;2-k

PubMed ID: 10025789

Title: A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures.

PubMed ID: 10025789

DOI: 10.1212/wnl.52.3.566

PubMed ID: 10208579

Title: Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene.

PubMed ID: 10208579

DOI: 10.1097/00001756-199902250-00011

PubMed ID: 10439444

Title: A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease.

PubMed ID: 10439444

DOI: 10.1097/00001756-199908020-00006

PubMed ID: 10631141

Title: High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.

PubMed ID: 10631141

DOI: 10.1086/302702

PubMed ID: 10644793

Title: Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy.

PubMed ID: 10644793

DOI: 10.1136/jnnp.68.2.220

PubMed ID: 11027672

Title: The presenilin 1 C92S mutation increases abeta 42 production.

PubMed ID: 11027672

DOI: 10.1006/bbrc.2000.3646

PubMed ID: 11094121

Title: Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation.

PubMed ID: 11094121

DOI: 10.1212/wnl.55.10.1577

PubMed ID: 11568920

Title: Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia.

PubMed ID: 11568920

DOI: 10.1002/1096-8628(20011001)103:2<138::aid-ajmg1529>3.0.co;2-8

PubMed ID: 11701593

Title: Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease due to a novel presenilin 1 mutation.

PubMed ID: 11701593

DOI: 10.1093/brain/124.12.2383

PubMed ID: 11710891

Title: A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.

PubMed ID: 11710891

DOI: 10.1001/jama.286.18.2257

PubMed ID: 11561050

Title: Very early onset Alzheimer's disease with spastic paraparesis associated with a novel presenilin 1 mutation (Phe237Ile).

PubMed ID: 11561050

DOI: 10.1136/jnnp.71.4.556

PubMed ID: 11524469

Title: Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.

PubMed ID: 11524469

DOI: 10.1212/wnl.57.4.621

PubMed ID: 11920851

Title: Molecular evidence of presenilin 1 mutation in familial early onset dementia.

PubMed ID: 11920851

DOI: 10.1002/ajmg.10250

PubMed ID: 11796781

Title: A novel mutation (V89L) in the presenilin 1 gene in a family with early onset Alzheimer's disease and marked behavioural disturbances.

PubMed ID: 11796781

DOI: 10.1136/jnnp.72.2.266

PubMed ID: 12370477

Title: Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities.

PubMed ID: 12370477

DOI: 10.1212/wnl.59.7.1108

PubMed ID: 12048239

Title: Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production.

PubMed ID: 12048239

DOI: 10.1073/pnas.112686799

PubMed ID: 12484344

Title: A novel presenilin 1 mutation (L174 M) in a large Cuban family with early onset Alzheimer disease.

PubMed ID: 12484344

DOI: 10.1007/s10048-002-0136-6

PubMed ID: 12493737

Title: Presenilin-1 mutation L271V results in altered exon 8 splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy.

PubMed ID: 12493737

DOI: 10.1074/jbc.m211827200

PubMed ID: 12552037

Title: Early onset familial Alzheimer's disease: Mutation frequency in 31 families.

PubMed ID: 12552037

DOI: 10.1212/01.wnl.0000042088.22694.e3

PubMed ID: 15122701

Title: A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques.

PubMed ID: 15122701

DOI: 10.1002/ana.20083

PubMed ID: 15534188

Title: A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis.

PubMed ID: 15534188

DOI: 10.1001/archneur.61.11.1773

PubMed ID: 15534260

Title: A presenilin 1 R278I mutation presenting with language impairment.

PubMed ID: 15534260

DOI: 10.1212/01.wnl.0000143060.98164.1a

PubMed ID: 15364419

Title: A novel presenilin 1 mutation (Y154N) in a patient with early onset Alzheimer's disease with spastic paraparesis.

PubMed ID: 15364419

DOI: 10.1016/j.neulet.2004.07.057

PubMed ID: 16344340

Title: Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life.

PubMed ID: 16344340

DOI: 10.1001/archneur.62.12.1821

PubMed ID: 15851849

Title: One novel presenilin-1 gene mutation in a Chinese pedigree of familial Alzheimer's disease.

PubMed ID: 15851849

DOI: 10.3233/jad-2005-7204

PubMed ID: 17186461

Title: Mutations of presenilin genes in dilated cardiomyopathy and heart failure.

PubMed ID: 17186461

DOI: 10.1086/509900

PubMed ID: 16752394

Title: Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40.

PubMed ID: 16752394

DOI: 10.1002/humu.20336

PubMed ID: 16628450

Title: Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer's disease in Mexican families.

PubMed ID: 16628450

DOI: 10.1007/s10048-006-0043-3

PubMed ID: 16897084

Title: The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families.

PubMed ID: 16897084

DOI: 10.1007/s10048-006-0053-1

PubMed ID: 17366635

Title: Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation.

PubMed ID: 17366635

DOI: 10.1002/ana.21099

PubMed ID: 17502474

Title: Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.

PubMed ID: 17502474

DOI: 10.1001/archneur.64.5.738

PubMed ID: 17428795

Title: Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor.

PubMed ID: 17428795

DOI: 10.1074/jbc.m611449200

PubMed ID: 18485326

Title: Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.

PubMed ID: 18485326

DOI: 10.1016/j.ajhg.2008.04.014

PubMed ID: 18430735

Title: Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta.

PubMed ID: 18430735

DOI: 10.1074/jbc.m801279200

PubMed ID: 19797784

Title: Novel PSEN1 mutation in a Bulgarian patient with very early-onset Alzheimer's disease, spastic paraparesis, and extrapyramidal signs.

PubMed ID: 19797784

DOI: 10.1177/1533317509341464

PubMed ID: 19667325

Title: Presenilin1 G217R mutation linked to Alzheimer disease with cotton wool plaques.

PubMed ID: 19667325

DOI: 10.1212/wnl.0b013e3181b163ba

PubMed ID: 20164095

Title: Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation.

PubMed ID: 20164095

DOI: 10.1212/wnl.0b013e3181d52785

PubMed ID: 20460383

Title: A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity.

PubMed ID: 20460383

DOI: 10.1074/jbc.m110.116962

PubMed ID: 21335660

Title: Clinical phenotype of G206D mutation in the presenilin 1 gene in pathologically confirmed familial Alzheimer's disease.

PubMed ID: 21335660

DOI: 10.3233/jad-2011-102031

PubMed ID: 21248752

Title: Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.

PubMed ID: 21248752

DOI: 10.1038/nature09639

PubMed ID: 21501661

Title: A novel PSEN1 gene mutation (L235R) associated with familial early-onset Alzheimer's disease.

PubMed ID: 21501661

DOI: 10.1016/j.neulet.2011.03.084

PubMed ID: 22461631

Title: Familial Alzheimer disease presenilin-1 mutations alter the active site conformation of gamma-secretase.

PubMed ID: 22461631

DOI: 10.1074/jbc.m111.300483

PubMed ID: 22503161

Title: Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients.

PubMed ID: 22503161

DOI: 10.1016/j.neurobiolaging.2012.02.020

PubMed ID: 23123781

Title: Novel presenilin-1 Y159F sequence variant associated with early-onset Alzheimer's disease.

PubMed ID: 23123781

DOI: 10.1016/j.neulet.2012.10.037

PubMed ID: 22529981

Title: Alzheimer's disease-linked mutations in presenilin-1 result in a drastic loss of activity in purified gamma-secretase complexes.

PubMed ID: 22529981

DOI: 10.1371/journal.pone.0035133

PubMed ID: 23843529

Title: Trans-dominant negative effects of pathogenic PSEN1 mutations on gamma-secretase activity and Abeta production.

PubMed ID: 23843529

DOI: 10.1523/jneurosci.0954-13.2013

PubMed ID: 24121961

Title: A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early onset and unusually fast progressing dementia as well as lysosomal inclusions typically seen in Kufs disease.

PubMed ID: 24121961

DOI: 10.3233/jad-131340

PubMed ID: 24495933

Title: Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease.

PubMed ID: 24495933

DOI: 10.1016/j.neulet.2014.01.016

PubMed ID: 24582897

Title: A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

PubMed ID: 24582897

DOI: 10.1016/j.neulet.2014.02.034

PubMed ID: 26145164

Title: Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease.

PubMed ID: 26145164

DOI: 10.1016/j.neurobiolaging.2015.06.007

PubMed ID: 27073747

Title: The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer's disease in Hispanics in Florida.

PubMed ID: 27073747

PubMed ID: 26549787

Title: Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late-onset Alzheimer's disease.

PubMed ID: 26549787

DOI: 10.1016/j.neulet.2015.11.004

PubMed ID: 28269784

Title: A novel PSEN1 K311R mutation discovered in Chinese families with late-onset Alzheimer's disease affects amyloid-beta production and tau phosphorylation.

PubMed ID: 28269784

DOI: 10.3233/jad-161188

PubMed ID: 27930341

Title: Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase.

PubMed ID: 27930341

DOI: 10.1073/pnas.1618657114

PubMed ID: 30200536

Title: PSEN1 p.Thr116Ile variant in two Korean families with young onset Alzheimer's disease.

PubMed ID: 30200536

DOI: 10.3390/ijms19092604

PubMed ID: 29404783

Title: Neuropathology and biochemistry of early onset familial Alzheimer's disease caused by presenilin-1 missense mutation Thr116Asn.

PubMed ID: 29404783

DOI: 10.1007/s00702-018-1850-z

PubMed ID: 29175279

Title: Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation.

PubMed ID: 29175279

DOI: 10.1016/j.neurobiolaging.2017.10.011

PubMed ID: 30180983

Title: Novel PSEN1 p.Gly417Ala mutation in a Korean patient with early-onset Alzheimer's disease with parkinsonism.

PubMed ID: 30180983

DOI: 10.1016/j.neurobiolaging.2018.08.003

PubMed ID: 29466804

Title: Phenotypic variability in autosomal dominant familial Alzheimer disease due to the S170F mutation of presenilin-1.

PubMed ID: 29466804

DOI: 10.1159/000485899

Sequence Information:

Length: 467
Mass: 52668
Checksum: 5E0F451EF82BCF20
Sequence:

MTELPAPLSY FQNAQMSEDN HLSNTVRSQN DNRERQEHND RRSLGHPEPL SNGRPQGNSR 
QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE 
DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI 
YLGEVFKTYN VAVDYITVAL LIWNFGVVGM ISIHWKGPLR LQQAYLIMIS ALMALVFIKY 
LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE 
GDPEAQRRVS KNSKYNAEST ERESQDTVAE NDDGGFSEEW EAQRDSHLGP HRSTPESRAA 
VQELSSSILA GEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL 
TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI

Genular Protein ID: 967208878

Symbol: A0A0S2Z4D2_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0S2Z4D2

Database IDs:

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 26871637

Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PubMed ID: 26871637

DOI: 10.1016/j.cell.2016.01.029

Sequence Information:

Length: 463
Mass: 52197
Checksum: 955325791A81470F
Sequence:

MTELPAPLSY FQNAQMSEDN HLSNTNDNRE RQEHNDRRSL GHPEPLSNGR PQGNSRQVVE 
QDEEEDEELT LKYGAKHVIM LFVPVTLCMV VVVATIKSVS FYTRKDGQLI YTPFTEDTET 
VGQRALHSIL NAAIMISVIV VMTILLVVLY KYRCYKVIHA WLIISSLLLL FFFSFIYLGE 
VFKTYNVAVD YITVALLIWN FGVVGMISIH WKGPLRLQQA YLIMISALMA LVFIKYLPEW 
TAWLILAVIS VYDLVAVLCP KGPLRMLVET AQERNETLFP ALIYSSTMVW LVNMAEGDPE 
AQRRVSKNSK YNAESTERES QDTVAENDDG GFSEEWEAQR DSHLGPHRST PESRAAVQEL 
SSSILAGEDP EERGVKLGLG DFIFYSVLVG KASATASGDW NTTIACFVAI LIGLCLTLLL 
LAIFKKALPA LPISITFGLV FYFATDYLVQ PFMDQLAFHQ FYI

	Overall overall
	Acute kidney failure MONDO0002492
	Adrenal gland UBERON0002369
	Alzheimer disease MONDO0004975
	Amyotrophic lateral sclerosis MONDO0004976
	Basal cell carcinoma MONDO0020804
	Bipolar disorder MONDO0004985
	Bipolar I disorder MONDO0001866
	Blood UBERON0000178
	\|— Blood COVID-19 UBERON0000178_MONDO0100096
	\|— Blood Cytomegalovirus infection UBERON0000178_MONDO0005132
	\|— Blood Healthy UBERON0000178_PATO0000461
	Body of stomach UBERON0001161
	Bone marrow UBERON0002371
	\|— Bone marrow Healthy UBERON0002371_PATO0000461
	Brain UBERON0000955
	\|— Brain Healthy UBERON0000955_PATO0000461
	Breast UBERON0000310
	\|— Breast cancer MONDO0007254
	Bronchus UBERON0002185
	Caudate lobe of liver UBERON0001117
	Cerebellum UBERON0002037
	\|— Cerebellum Healthy UBERON0002037_PATO0000461
	Cerebral cortex UBERON0000956
	\|— Cerebral cortex Healthy UBERON0000956_PATO0000461
	Cerebrospinal fluid UBERON0001359
	Choroid plexus UBERON0001886
	Chronic kidney disease MONDO0005300
	Colon UBERON0001155
	\|— Colon Healthy UBERON0001155_PATO0000461
	Colorectal cancer MONDO0005575
	Cortex of kidney UBERON0001225
	\|— Cortex of kidney Healthy UBERON0001225_PATO0000461
	COVID-19 MONDO0100096
	Crohn disease MONDO0005011
	Cytomegalovirus infection MONDO0005132
	Dementia MONDO0001627
	Dorsolateral prefrontal cortex UBERON0009834
	\|— Dorsolateral prefrontal cortex Bipolar disorder UBERON0009834_MONDO0004985
	\|— Dorsolateral prefrontal cortex Bipolar I disorder UBERON0009834_MONDO0001866
	\|— Dorsolateral prefrontal cortex Dementia UBERON0009834_MONDO0001627
	\|— Dorsolateral prefrontal cortex Healthy UBERON0009834_PATO0000461
	\|— Dorsolateral prefrontal cortex Schizophrenia UBERON0009834_MONDO0005090
	\|— Dorsolateral prefrontal cortex Vascular dementia UBERON0009834_MONDO0004648
	Frontal cortex UBERON0001870
	Glioblastoma MONDO0018177
	Healthy PATO0000461
	Heart left ventricle UBERON0002084
	\|— Heart left ventricle Healthy UBERON0002084_PATO0000461
	Heart right ventricle UBERON0002080
	\|— Heart right ventricle Healthy UBERON0002080_PATO0000461
	Hippocampal formation UBERON0002421
	\|— Hippocampal formation Healthy UBERON0002421_PATO0000461
	Hypothalamus UBERON0001898
	\|— Hypothalamus Healthy UBERON0001898_PATO0000461
	Ileum UBERON0002116
	\|— Ileum Healthy UBERON0002116_PATO0000461
	Interventricular septum UBERON0002094
	Isolated focal cortical dysplasia type II MONDO0011818
	Kidney UBERON0002113
	\|— Kidney Healthy UBERON0002113_PATO0000461
	Leukoencephalopathy, diffuse hereditary, with spheroids 1 MONDO0800027
	Liver UBERON0002107
	\|— Liver Healthy UBERON0002107_PATO0000461
	Lung UBERON0002048
	\|— Lung Healthy UBERON0002048_PATO0000461
	\|— Lung adenocarcinoma MONDO0005061
	Lymph node UBERON0000029
	Medial orbital frontal cortex UBERON0022352
	Midbrain UBERON0001891
	\|— Midbrain Healthy UBERON0001891_PATO0000461
	Nasopharynx UBERON0001728
	Neocortex UBERON0001950
	\|— Neocortex Healthy UBERON0001950_PATO0000461
	Neuroblastoma MONDO0005072
	Occipital cortex UBERON0016540
	Pancreas UBERON0001264
	\|— Pancreas Healthy UBERON0001264_PATO0000461
	Parkinson disease MONDO0005180
	Peripheral region of retina UBERON0013682
	\|— Peripheral region of retina Healthy UBERON0013682_PATO0000461
	Placenta UBERON0001987
	Pleural effusion UBERON0000175
	Pons UBERON0000988
	\|— Pons Healthy UBERON0000988_PATO0000461
	Prefrontal cortex UBERON0000451
	Primary motor cortex UBERON0001384
	\|— Primary motor cortex Healthy UBERON0001384_PATO0000461
	Renal medulla UBERON0000362
	\|— Renal medulla Healthy UBERON0000362_PATO0000461
	Respiratory airway UBERON0001005
	\|— Respiratory airway COVID-19 UBERON0001005_MONDO0100096
	Retina UBERON0000966
	\|— Retina Healthy UBERON0000966_PATO0000461
	Right atrium auricular region UBERON0006631
	Schizophrenia MONDO0005090
	Sigmoid colon UBERON0001159
	Skin of body UBERON0002097
	\|— Skin of body Healthy UBERON0002097_PATO0000461
	Small cell lung carcinoma MONDO0008433
	Spleen UBERON0002106
	\|— Spleen Healthy UBERON0002106_PATO0000461
	Substantia nigra pars compacta UBERON0001965
	Telencephalon UBERON0001893
	\|— Telencephalon Healthy UBERON0001893_PATO0000461
	Thalamic complex UBERON0010225
	\|— Thalamic complex Healthy UBERON0010225_PATO0000461
	Trachea UBERON0003126
	UBERON0005290 UBERON0005290
	\|— UBERON0005290 Healthy UBERON0005290_PATO0000461
	UBERON8440012 UBERON8440012
	\|— UBERON8440012 Healthy UBERON8440012_PATO0000461
	Vascular dementia MONDO0004648

Details for: PSEN1

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. PubMed ID: 7596406

Identification and characterization of presenilin I-467, I-463 and I-374. PubMed ID: 8641442

Complete sequencing and characterization of 21,243 full-length human cDNAs. PubMed ID: 14702039

The DNA sequence and analysis of human chromosome 14. PubMed ID: 12508121

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). PubMed ID: 15489334

Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential expression in oogenesis and embryogenesis. PubMed ID: 9070286

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. Identification of a novel splice variant. PubMed ID: 8804415

Purification and characterization of the human gamma-secretase complex. PubMed ID: 15274632

Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. PubMed ID: 8574969

Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue. PubMed ID: 9173929

Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C. PubMed ID: 9144240

Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa C-terminal fragment are death substrates for proteases of the caspase family. PubMed ID: 9485372

Direct association of presenilin-1 with beta-catenin. PubMed ID: 9738936

Interaction of presenilins with the filamin family of actin-binding proteins. PubMed ID: 9437013

Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis. PubMed ID: 10545183

Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1. PubMed ID: 10551805

Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch. PubMed ID: 10593990

Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin. PubMed ID: 10037471

Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. PubMed ID: 10206644

Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling. PubMed ID: 10899933

Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch. PubMed ID: 10811883

Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules. PubMed ID: 11987239

A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. PubMed ID: 11953314

Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. PubMed ID: 11799129

A new splice variant of glial fibrillary acidic protein GFAPepsilon, interacts with the presenilin proteins. PubMed ID: 12058025

Presenilin 1 is involved in maturation and trafficking of N-cadherin to the plasma membrane. PubMed ID: 14515347

Reconstitution of gamma-secretase activity. PubMed ID: 12679784

Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. PubMed ID: 12740439

An unappreciated role for RNA surveillance. PubMed ID: 14759258

A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations. PubMed ID: 15004326

Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis. PubMed ID: 14576165

Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins. PubMed ID: 15385547

Conserved residues within the putative active site of gamma-secretase differentially influence enzyme activity and inhibitor binding. PubMed ID: 15341515

Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability. PubMed ID: 16126725

Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. PubMed ID: 17081983

Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. PubMed ID: 16959576

C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation. PubMed ID: 16305624

The presenilin genes: a new gene family involved in Alzheimer disease pathology. PubMed ID: 8875251

Presenilin mutations in Alzheimer's disease. PubMed ID: 9521418

Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. PubMed ID: 18691976

A quantitative atlas of mitotic phosphorylation. PubMed ID: 18669648

Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. PubMed ID: 19690332

Human CRB2 inhibits gamma-secretase cleavage of amyloid precursor protein by binding to the presenilin complex. PubMed ID: 20299451

Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. PubMed ID: 20068231

Gamma-secretase gene mutations in familial acne inversa. PubMed ID: 20929727

System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. PubMed ID: 21406692

Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation. PubMed ID: 21143716

Toward a comprehensive characterization of a human cancer cell phosphoproteome. PubMed ID: 23186163

G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation. PubMed ID: 25394380

Three-dimensional structure of human gamma-secretase. PubMed ID: 25043039

Sampling the conformational space of the catalytic subunit of human gamma-secretase. PubMed ID: 26623517

An atomic structure of human gamma-secretase. PubMed ID: 26280335

Structural basis of human gamma-secretase assembly. PubMed ID: 25918421

Structural basis of Notch recognition by human gamma-secretase. PubMed ID: 30598546

Recognition of the amyloid precursor protein by human gamma-secretase. PubMed ID: 30630874

Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3. PubMed ID: 8634711

Mutations of the presenilin I gene in families with early-onset Alzheimer's disease. PubMed ID: 8634712

Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. PubMed ID: 7651536

The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. PubMed ID: 7550356

The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 deposition and severe cerebellar pathology. PubMed ID: 8837617

Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families. PubMed ID: 8733303

Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation. PubMed ID: 9225696

E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles. PubMed ID: 9298817

Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype. PubMed ID: 9172170

A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer disease. PubMed ID: 9833068

The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease. PubMed ID: 9851443

Missense mutation E318G of the presenilin-1 gene appears to be a nonpathogenic polymorphism. PubMed ID: 9851450

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. PubMed ID: 9384602

Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. PubMed ID: 9521423

Missense mutation in exon 11 (codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer's disease and transmission study by mismatch enhanced allele specific amplification. PubMed ID: 10200054

De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer's disease cases. PubMed ID: 9719376

A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years. PubMed ID: 9507958

Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease. PubMed ID: 9831473