PSEN1 Gene (Protein Coding)

Presenilin 1

GC14P073136
GIFtS:
53
Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing... See more...

Aliases for PSEN1 Gene

Aliases for PSEN1 Gene

  • Presenilin 1 2 3 5
  • PS1 2 3 4
  • Presenilin-1 3 4
  • PS-1 3 4
  • S182 2 3
  • AD3 3 4
  • FAD 2 3
  • Alzheimer Disease 3 2
  • Protein S182 4
  • EC 3.4.23.- 4
  • EC 3.4.23 51
  • ACNINV3 3
  • PSEN1 5
  • PSNL1 4

External Ids for PSEN1 Gene

Previous HGNC Symbols for PSEN1 Gene

  • AD3

Previous GeneCards Identifiers for PSEN1 Gene

  • GC14P071108
  • GC14P067398
  • GC14P071592
  • GC14P071593
  • GC14P072672
  • GC14P073603
  • GC14P053768

Summaries for PSEN1 Gene

Entrez Gene Summary for PSEN1 Gene

  • Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]

GeneCards Summary for PSEN1 Gene

PSEN1 (Presenilin 1) is a Protein Coding gene. Diseases associated with PSEN1 include Pick Disease Of Brain and Alzheimer Disease 3. Among its related pathways are IL-2 Pathway and Degradation of the extracellular matrix. Gene Ontology (GO) annotations related to this gene include peptidase activity and beta-catenin binding. An important paralog of this gene is ENSG00000288674.

UniProtKB/Swiss-Prot Summary for PSEN1 Gene

  • 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:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874, PubMed:28269784, PubMed:20460383). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis (PubMed:25394380, PubMed:16959576). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).

Tocris Summary for PSEN1 Gene

  • gamma-secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1 and PEN-2. gamma-secretase is involved in the processing of Notch.

Gene Wiki entry for PSEN1 Gene

Additional gene information for PSEN1 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PSEN1 Gene

Genomics for PSEN1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for PSEN1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PSEN1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PSEN1

Top Transcription factor binding sites by QIAGEN in the PSEN1 gene promoter:
  • AML1a
  • AREB6
  • Cart-1
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for PSEN1 Gene

Latest Assembly
chr14:73,136,418-73,223,691
(GRCh38/hg38)
Size:
87,274 bases
Orientation:
Plus strand

Previous Assembly
chr14:73,603,215-73,690,399
(GRCh37/hg19 by Entrez Gene)
Size:
87,185 bases
Orientation:
Plus strand

chr14:73,603,126-73,690,399
(GRCh37/hg19 by Ensembl)
Size:
87,274 bases
Orientation:
Plus strand

Genomic View for PSEN1 Gene

Genes around PSEN1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PSEN1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PSEN1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for PSEN1 Gene

Proteins for PSEN1 Gene

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  • Protein details for PSEN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49768-PSN1_HUMAN
    Recommended name:
    Presenilin-1
    Protein Accession:
    P49768
    Secondary Accessions:
    • B2R6D3
    • O95465
    • Q14762
    • Q15719
    • Q15720
    • Q96P33
    • Q9UIF0

    Protein attributes for PSEN1 Gene

    Size:
    467 amino acids
    Molecular mass:
    52668 Da
    Quaternary structure:
    • Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2 (PubMed:15274632, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:25394380, PubMed:30598546, PubMed:30630874). Such minimal complex is sufficient for secretase activity (PubMed:15274632, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). Other components which are associated with the complex include SLC25A64, SLC5A7, PHB and PSEN1 isoform 3. As part of the gamma-secretase complex, interacts with CRB2 (via transmembrane domain) (PubMed:20299451). Predominantly heterodimer of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment (PubMed:15274632). Associates with proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP) (via transmembrane domain) (PubMed:30630874). Associates with NOTCH1 (via transmembrane domain) (PubMed:10593990, PubMed:30598546). Associates with cadherin/catenin adhesion complexes through direct binding to CDH1 or CDH2 (PubMed:11953314, PubMed:14515347, PubMed:16126725). Interaction with CDH1 stabilizes the complex and stimulates cell-cell aggregation (PubMed:11953314). Interaction with CDH2 is essential for trafficking of CDH2 from the endoplasmic reticulum to the plasma membrane (PubMed:14515347). Interacts with CTNND2, CTNNB1, CTNND1, JUP, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL (PubMed:9738936, PubMed:9437013, PubMed:10551805, PubMed:10037471, PubMed:11953314, PubMed:11799129, PubMed:16126725). Interacts through its N-terminus with isoform 3 of GFAP (PubMed:12058025). Interacts with DOCK3 (By similarity). Interacts with isoform 1 and isoform 3 of UBQLN1 (PubMed:21143716).
    Miscellaneous:
    • [Isoform 3]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Three dimensional structures from OCA and Proteopedia for PSEN1 Gene

    Alternative splice isoforms for PSEN1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PSEN1 Gene

Protein Expression for PSEN1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for PSEN1 Gene

P49768:
  • EELTLKYGA
  • AILIGLCLTLLLLA
  • ALMALVFIKYLPEW
  • SGDWNTT
  • IMISVIVVMT
  • ISVYDLVAVL
  • VPVTLCM
  • FKKALPALP
  • LGPHRST
  • DDGGFSEEWEAQRDS
  • EERGVKLGLGDF
  • PFMDQLA
  • PEPLSNGRPQG
  • ETAQERN
  • IHWKGPL
  • KLGLGDFIFYS
  • LGEVFKTYNVA
  • EDTETVGQRALHS
  • WNFGVVGM
  • DYITVAL
  • LQQAYLI
  • VVVATIKSV
  • PAPLSYFQNAQMSED
  • LYKYRCYK
  • FPALIYSS
  • AVLCPKGPLR
  • GQLIYTPFTE

Post-translational modifications for PSEN1 Gene

  • Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by caspase-3 to produce the fragment, PS1-CTF12.
  • After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-346 inhibits endoproteolysis.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PSEN1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

Domains & Families for PSEN1 Gene

Gene Families for PSEN1 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Transporters

Protein Domains for PSEN1 Gene

InterPro:
Blocks:
  • Presenilin 1 signature
  • Presenilin signal peptide peptidase
ProtoNet:

Suggested Antigen Peptide Sequences for PSEN1 Gene

GenScript: Design optimal peptide antigens:
  • Protein S182 (PSN1_HUMAN)
  • Presenilin 1 (Q6F4C0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P49768

UniProtKB/Swiss-Prot:

PSN1_HUMAN :
  • The PAL motif is required for normal active site conformation.
  • Belongs to the peptidase A22A family.
Domain:
  • The PAL motif is required for normal active site conformation.
  • Substrates, such as NOTCH1 and APP peptides, are bound between PSEN1 transmembrane domains and via the first lumenal loop and the cytoplasmic loop between the sixth and seventh transmembrane domains. Substrate binding causes a conformation change and formation of an intermolecular antiparallel beta-sheet between PSEN1 and its substrates.
Family:
  • Belongs to the peptidase A22A family.
genes like me logo Genes that share domains with PSEN1: view

Function for PSEN1 Gene

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  6. Cell Lines for research

Molecular function for PSEN1 Gene

UniProtKB/Swiss-Prot Function:
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:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874, PubMed:28269784, PubMed:20460383). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis (PubMed:25394380, PubMed:16959576). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).
GENATLAS Biochemistry:
presenilin 1,forming a multimeric complex that contains catenin beta (CTNNB1) and delta (CTNND1),widely expressed at low levels within the CNS,predominantly in the neocortex,dentate gyrus,hippocampus,cerebellar cortex,deep nuclei,also expressed in other organs,predominantly located in intracellular membranous organelles such as nuclear envelope,endoplasmic reticulum and Golgi apparatus with two alternatively variants,spliced in exon 3 (VRSQ) and in exon 8,but not involved in the protein transport from endoplasmic reticulum to the Golgi apparatus,membrane receptor for GDI1 and may be involved in the cleavage of APP and NOTCHs,interacting with Rab11 and may be involved in APP vesicular trafficking homologous to C elegans SPE-4,putative susceptibility factor for early onset EOAA independent of APOE4 and for late onset AD,both associated with the -48C->T polymorphism

Enzyme Numbers (IUBMB) for PSEN1 Gene

Phenotypes From GWAS Catalog for PSEN1 Gene

Gene Ontology (GO) - Molecular Function for PSEN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IDA,IMP 12297508
GO:0004190 aspartic-type endopeptidase activity IEA,NAS 24217950
GO:0005262 calcium channel activity IMP 16959576
GO:0005515 protein binding IPI 9223340
GO:0008013 beta-catenin binding IPI 9632714
genes like me logo Genes that share ontologies with PSEN1: view
genes like me logo Genes that share phenotypes with PSEN1: view

Human Phenotype Ontology for PSEN1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PSEN1 Gene

MGI Knock Outs for PSEN1:

Animal Models for research

  • Taconic Biosciences Mouse Models for PSEN1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PSEN1

Clone products for research

No data available for Transcription Factor Targets and HOMER Transcription for PSEN1 Gene

Localization for PSEN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PSEN1 Gene

Endoplasmic reticulum. Endoplasmic reticulum membrane. Multi-pass membrane protein. Golgi apparatus membrane. Multi-pass membrane protein. Cytoplasmic granule. Cell membrane. Multi-pass membrane protein. Cell projection, growth cone. Early endosome. Early endosome membrane. Multi-pass membrane protein. Cell projection, neuron projection. Cell projection, axon. Cell junction, synapse. Note=Translocates with bound NOTCH1 from the endoplasmic reticulum and/or Golgi to the cell surface (PubMed:10593990). Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane (PubMed:9738936). Also present in azurophil granules of neutrophils (PubMed:11987239). Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes (PubMed:21143716). {ECO:0000269 PubMed:10593990, ECO:0000269 PubMed:11987239, ECO:0000269 PubMed:21143716, ECO:0000269 PubMed:9738936}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PSEN1 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 5
mitochondrion 5
nucleus 5
endoplasmic reticulum 5
lysosome 5
golgi apparatus 5
endosome 4
extracellular 3
cytosol 3
peroxisome 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (3)
  • Golgi apparatus (3)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PSEN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0000776 kinetochore IDA 9298903
GO:0005634 nucleus IMP 10508860
GO:0005640 nuclear outer membrane IDA 9246482
GO:0005654 nucleoplasm IDA --
genes like me logo Genes that share ontologies with PSEN1: view

Pathways & Interactions for PSEN1 Gene

genes like me logo Genes that share pathways with PSEN1: view

Pathways by source for PSEN1 Gene

3 GeneGo (Thomson Reuters) pathways for PSEN1 Gene
  • Development MAG-dependent inhibition of neurite outgrowth
  • Development Notch Signaling Pathway
  • Development NOTCH1-mediated pathway for NF-KB activity modulation
1 Tocris pathway for PSEN1 Gene
5 Qiagen pathways for PSEN1 Gene
  • Alzheimers Disease Pathway
  • ErbB4 Pathway
  • Molecular Mechanisms of Cancer
  • Notch Signaling
  • Presenilin-Mediated Signaling
2 Cell Signaling Technology pathways for PSEN1 Gene
1 GeneTex pathway for PSEN1 Gene

SIGNOR curated interactions for PSEN1 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for PSEN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000045 autophagosome assembly IEA --
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 10508860
GO:0000186 activation of MAPKK activity IEA --
GO:0001568 blood vessel development IEA --
GO:0001708 cell fate specification IEA --
genes like me logo Genes that share ontologies with PSEN1: view

Drugs & Compounds for PSEN1 Gene

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(53) Drugs for PSEN1 Gene - From: ApexBio, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Avagacestat Investigational Pharma 0
Begacestat Investigational Pharma γ-secretase inhibitor 0
GSI-136 Investigational Pharma 0
Semagacestat Investigational Pharma 0
BMS 299897 Pharma γ--secretase inhibitor, potent and orally active, Potent gamma-secretase inhibitor 0

(28) Additional Compounds for PSEN1 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Compound W
173550-33-9
DAPT
208255-80-5

(5) Tocris Compounds for PSEN1 Gene

Compound Action Cas Number
BMS 299897 Potent gamma-secretase inhibitor 290315-45-6
Compound W gamma-secretase inhibitor 173550-33-9
DAPT gamma-secretase inhibitor 208255-80-5
JLK 6 Inhibitor of gamma-secretase-mediated betaAPP processing 62252-26-0
L-685,458 Potent and selective gamma-secretase inhibitor 292632-98-5

(1) ApexBio Compounds for PSEN1 Gene

Compound Action Cas Number
BMS 299897 γ--secretase inhibitor, potent and orally active 290315-45-6
genes like me logo Genes that share compounds with PSEN1: view

Drug products for research

Transcripts for PSEN1 Gene

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mRNA/cDNA for PSEN1 Gene

3 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
25 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PSEN1

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for PSEN1 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c · 2d · 2e ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b · 7c · 7d · 7e · 7f ^ 8 ^ 9a · 9b · 9c · 9d · 9e ^ 10a ·
SP1: - - - - - - - -
SP2: - - - - - - -
SP3: - - - - - - -
SP4: - -
SP5: -
SP6:
SP7: - - - - - - - - - -
SP8: - - - - - - - -
SP9: - - - - - -
SP10: - - - - - - - - - - - - -
SP11: - - - - - -
SP12: - - - - - - -
SP13: - - - - - - -
SP14: - - - - - -
SP15: - - - - - - -
SP16: - - - - - - -
SP17: - - - - -
SP18: - - -
SP19: - - - - - - -
SP20:
SP21: - - - -
SP22:

ExUns: 10b · 10c · 10d · 10e ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15 ^ 16a · 16b ^ 17a · 17b ^ 18a · 18b · 18c
SP1: - - -
SP2: - - -
SP3: - - -
SP4: - -
SP5: - -
SP6: - - -
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:
SP19:
SP20: -
SP21:
SP22: - -

Relevant External Links for PSEN1 Gene

GeneLoc Exon Structure for
PSEN1

Expression for PSEN1 Gene

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  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PSEN1 Gene

mRNA expression in normal human tissues for PSEN1 Gene
mRNA expression by BioGPS for PSEN1 GenemRNA expression by GTEx for PSEN1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PSEN1 Gene

This gene is overexpressed in Whole Blood (x4.2).

Protein differential expression in normal tissues from HIPED for PSEN1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (11.6), Monocytes (10.5), and Pancreas (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PSEN1 Gene



Protein tissue co-expression partners for PSEN1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PSEN1

SOURCE GeneReport for Unigene cluster for PSEN1 Gene:

Hs.3260

mRNA Expression by UniProt/SwissProt for PSEN1 Gene:

P49768-PSN1_HUMAN
Tissue specificity: Detected in azurophile granules in neutrophils and in platelet cytoplasmic granules (at protein level) (PubMed:11987239). Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes (PubMed:7596406, PubMed:8641442, PubMed:8574969).

Evidence on tissue expression from TISSUES for PSEN1 Gene

  • Nervous system(5)
  • Blood(4.6)
  • Skin(4.6)
  • Intestine(4.5)
  • Kidney(2.8)
  • Adrenal gland(2.7)
  • Heart(2.7)
  • Liver(2.6)
  • Muscle(2.6)
  • Spleen(2.5)
  • Bone marrow(2.4)
  • Lung(2.4)
  • Lymph node(2.4)
  • Thyroid gland(2.4)
  • Stomach(2.3)
  • Eye(2.3)
  • Pancreas(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PSEN1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • nose
  • pharynx
  • skull
  • tongue
Thorax:
  • esophagus
  • heart
  • heart valve
  • lung
Abdomen:
  • stomach
Pelvis:
  • prostate
  • urinary bladder
Limb:
  • foot
  • lower limb
  • upper limb
General:
  • blood
  • blood vessel
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with PSEN1: view

Orthologs for PSEN1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for PSEN1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia PSEN1 30 31
  • 99.86 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia PSEN1 30 31
  • 91.92 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia PSEN1 30 31
  • 90.65 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Psen1 30
  • 87.98 (n)
Mouse
(Mus musculus)
 Mammalia Psen1 30 17 31
  • 87.15 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia PSEN1 31
  • 87 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia -- 31
  • 80 (a)
 OneToMany
-- 31
  • 59 (a)
 OneToMany
Chicken
(Gallus gallus)
 Aves PSEN1 30 31
  • 77.47 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia PSEN1 31
  • 79 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia psen1 30
  • 75.27 (n)
LOC394924 30
African clawed frog
(Xenopus laevis)
 Amphibia Xl.1253 30
Zebrafish
(Danio rerio)
 Actinopterygii psen1 30 31
  • 70.82 (n)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta Psn 31 32
  • 44 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea sel-12 30 31 32
  • 56.46 (n)
 ManyToMany
hop-1 31
  • 33 (a)
 ManyToMany
spe-4 31
  • 20 (a)
 ManyToMany
Thale Cress
(Arabidopsis thaliana)
 eudicotyledons PS1 30
  • 46.97 (n)
Rice
(Oryza sativa)
 Liliopsida Os03g0603700 30
  • 45.98 (n)
Sea Squirt
(Ciona savignyi)
 Ascidiacea CSA.1400 31
  • 62 (a)
 OneToMany
Sea Vase
(Ciona intestinalis)
 Ascidiacea Cin.7776 30
Species where no ortholog for PSEN1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PSEN1 Gene

ENSEMBL:
Gene Tree for PSEN1 (if available)
TreeFam:
Gene Tree for PSEN1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PSEN1: view image

Paralogs for PSEN1 Gene

Paralogs for PSEN1 Gene

(3) SIMAP similar genes for PSEN1 Gene using alignment to 16 proteins:

  • PSN1_HUMAN
  • E7ES96_HUMAN
  • G3V2B1_HUMAN
  • G3V2G7_HUMAN
  • G3V3P0_HUMAN
  • G3V3Z0_HUMAN
  • G3V449_HUMAN
  • G3V490_HUMAN
  • G3V499_HUMAN
  • G3V4M0_HUMAN
  • G3V4P4_HUMAN
  • G3V519_HUMAN
  • G3V5B1_HUMAN
  • H0YM52_HUMAN
  • H0YNU4_HUMAN
  • Q6F4C0_HUMAN
genes like me logo Genes that share paralogs with PSEN1: view

Variants for PSEN1 Gene

Products:

  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PSEN1 Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
841495 Uncertain Significance: Frontotemporal dementia; Pick's disease; Alzheimer disease, type 3; Acne inversa, familial, 3 73,170,978(+) C/G
NM_000021.4(PSEN1):c.269C>G (p.Thr90Ser) 		MISSENSE
844411 Uncertain Significance: Frontotemporal dementia; Pick's disease; Alzheimer disease, type 3; Acne inversa, familial, 3 73,186,881(+) C/A
NM_000021.4(PSEN1):c.509C>A (p.Ser170Tyr) 		MISSENSE
845851 Pathogenic: Frontotemporal dementia; Pick's disease; Alzheimer disease, type 3; Acne inversa, familial, 3 73,219,139(+) G/C
NM_000021.4(PSEN1):c.1254G>C (p.Leu418Phe) 		MISSENSE
853657 Uncertain Significance: Frontotemporal dementia; Pick's disease; Alzheimer disease, type 3; Acne inversa, familial, 3 73,219,204(+) C/A
NM_000021.4(PSEN1):c.1319C>A (p.Thr440Asn) 		MISSENSE
861139 Uncertain Significance: Frontotemporal dementia; Pick's disease; Alzheimer disease, type 3; Acne inversa, familial, 3 73,173,702(+) T/C
NM_000021.4(PSEN1):c.475T>C (p.Tyr159His) 		MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PSEN1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PSEN1 Gene

Variant ID Type Subtype PubMed ID
esv3551762 CNV deletion 23714750
nsv1035460 CNV gain 25217958
nsv1049819 CNV gain 25217958
nsv479045 CNV novel sequence insertion 20440878
nsv507760 OTHER sequence alteration 20534489

Variation tolerance for PSEN1 Gene

Residual Variation Intolerance Score: 42.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.58; 30.57% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PSEN1 Gene

Human Gene Mutation Database (HGMD)
PSEN1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PSEN1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PSEN1 Gene

Disorders for PSEN1 Gene

MalaCards: The human disease database

(59) MalaCards diseases for PSEN1 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search PSEN1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PSN1_HUMAN
  • Alzheimer disease 3 (AD3) [MIM:607822]: A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269 PubMed:10025789, ECO:0000269 PubMed:10090481, ECO:0000269 PubMed:10200054, ECO:0000269 PubMed:10208579, ECO:0000269 PubMed:10439444, ECO:0000269 PubMed:10441572, ECO:0000269 PubMed:10447269, ECO:0000269 PubMed:10533070, ECO:0000269 PubMed:10631141, ECO:0000269 PubMed:10644793, ECO:0000269 PubMed:11027672, ECO:0000269 PubMed:11524469, ECO:0000269 PubMed:11561050, ECO:0000269 PubMed:11568920, ECO:0000269 PubMed:11701593, ECO:0000269 PubMed:11710891, ECO:0000269 PubMed:11796781, ECO:0000269 PubMed:11920851, ECO:0000269 PubMed:12048239, ECO:0000269 PubMed:12058025, ECO:0000269 PubMed:12370477, ECO:0000269 PubMed:12484344, ECO:0000269 PubMed:12493737, ECO:0000269 PubMed:12552037, ECO:0000269 PubMed:15004326, ECO:0000269 PubMed:15122701, ECO:0000269 PubMed:15364419, ECO:0000269 PubMed:15534188, ECO:0000269 PubMed:15534260, ECO:0000269 PubMed:15851849, ECO:0000269 PubMed:16305624, ECO:0000269 PubMed:16344340, ECO:0000269 PubMed:16628450, ECO:0000269 PubMed:16752394, ECO:0000269 PubMed:16897084, ECO:0000269 PubMed:16959576, ECO:0000269 PubMed:17366635, ECO:0000269 PubMed:17428795, ECO:0000269 PubMed:17502474, ECO:0000269 PubMed:18430735, ECO:0000269 PubMed:19667325, ECO:0000269 PubMed:19797784, ECO:0000269 PubMed:20164095, ECO:0000269 PubMed:20460383, ECO:0000269 PubMed:21335660, ECO:0000269 PubMed:21501661, ECO:0000269 PubMed:22461631, ECO:0000269 PubMed:22503161, ECO:0000269 PubMed:22529981, ECO:0000269 PubMed:23123781, ECO:0000269 PubMed:23843529, ECO:0000269 PubMed:24121961, ECO:0000269 PubMed:24495933, ECO:0000269 PubMed:24582897, ECO:0000269 PubMed:25394380, ECO:0000269 PubMed:26145164, ECO:0000269 PubMed:26280335, ECO:0000269 PubMed:26549787, ECO:0000269 PubMed:27073747, ECO:0000269 PubMed:27930341, ECO:0000269 PubMed:29175279, ECO:0000269 PubMed:29404783, ECO:0000269 PubMed:29466804, ECO:0000269 PubMed:30180983, ECO:0000269 PubMed:30200536, ECO:0000269 PubMed:7550356, ECO:0000269 PubMed:7596406, ECO:0000269 PubMed:7651536, ECO:0000269 PubMed:8634711, ECO:0000269 PubMed:8634712, ECO:0000269 PubMed:8733303, ECO:0000269 PubMed:8837617, ECO:0000269 PubMed:9172170, ECO:0000269 PubMed:9225696, ECO:0000269 PubMed:9298817, ECO:0000269 PubMed:9384602, ECO:0000269 PubMed:9507958, ECO:0000269 PubMed:9521423, ECO:0000269 PubMed:9719376, ECO:0000269 PubMed:9831473, ECO:0000269 PubMed:9833068, ECO:0000269 Ref.93}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Frontotemporal dementia (FTD) [MIM:600274]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269 PubMed:11094121}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Cardiomyopathy, dilated 1U (CMD1U) [MIM:613694]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269 PubMed:17186461, ECO:0000269 PubMed:27930341}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Acne inversa, familial, 3 (ACNINV3) [MIM:613737]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269 PubMed:20929727}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Pick disease of the brain (PIDB) [MIM:172700]: A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration. {ECO:0000269 PubMed:15122701}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Additional Disease Information for PSEN1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with PSEN1: view

No data available for Genatlas for PSEN1 Gene

Publications for PSEN1 Gene

  1. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. (PMID: 7550356) Alzheimer's Disease Collaborative Group (Nature genetics 1995) 3 4 23 74
  2. Gamma-secretase gene mutations in familial acne inversa. (PMID: 20929727) Wang B … Zhang X (Science (New York, N.Y.) 2010) 3 4 74
  3. Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. (PMID: 18667258) Guerreiro RJ … Clarimón J (Neurobiology of aging 2010) 3 23 41
  4. Assessment of Alzheimer's disease case-control associations using family-based methods. (PMID: 18830724) Schjeide BM … Bertram L (Neurogenetics 2009) 3 23 41
  5. High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. (PMID: 20008660) Villemagne VL … Rowe CC (Archives of neurology 2009) 3 23 41

ExternalLinks

View latest publications for PSEN1 gene in Mastermind

Products for PSEN1 Gene

  • Biorbyt antibodies for PSEN1