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APP Gene(Protein Coding)

Amyloid Beta Precursor Protein

GCID:
GC21M025880
GIFtS:
59
Genes Participants
UDN Logo

Aliases for APP Gene

Aliases for APP Gene

  • Amyloid Beta Precursor Protein 2 3 5
  • Amyloid Beta (A4) Precursor Protein 2 3
  • Alzheimer Disease Amyloid Protein 3 4
  • Cerebral Vascular Amyloid Peptide 3 4
  • Amyloid Precursor Protein 3 4
  • Peptidase Nexin-II 2 3
  • Protease Nexin-II 3 4
  • PreA4 3 4
  • PN-II 3 4
  • ABPP 3 4
  • APPI 3 4
  • CVAP 3 4
  • AD1 3 4
  • Beta-Amyloid Precursor Protein 3
  • Testicular Tissue Protein Li 2 3
  • Amyloid-Beta Precursor Protein 4
  • Beta-Amyloid Peptide(1-40) 3
  • Beta-Amyloid Peptide(1-42) 3
  • Amyloid Beta A4 Protein 3
  • Amyloid-Beta A4 Protein 3
  • Beta-Amyloid Peptide 3
  • Alzheimer Disease 2
  • CTFgamma 3
  • ABETA 3
  • AAA 3
  • PN2 3
  • A4 4

External Ids for APP Gene

Previous HGNC Symbols for APP Gene

  • AD1

Previous GeneCards Identifiers for APP Gene

  • GC21M023831
  • GC21M026174
  • GC21M027252
  • GC21M012656

Summaries for APP Gene

Entrez Gene Summary for APP Gene

  • This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2014]

GeneCards Summary for APP Gene

APP (Amyloid Beta Precursor Protein) is a Protein Coding gene. Diseases associated with APP include Cerebral Amyloid Angiopathy, App-Related and Alzheimer Disease. Among its related pathways are Activated TLR4 signalling and Reelin Pathway (Cajal-Retzius cells). Gene Ontology (GO) annotations related to this gene include identical protein binding and enzyme binding. An important paralog of this gene is APLP2.

UniProtKB/Swiss-Prot for APP Gene

  • Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.

  • Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.

  • Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.

  • The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.

  • N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).

Tocris Summary for APP Gene

  • Amyloid beta (Abeta) peptides are the major component of amyloid plaques found in the brains of Alzheimer's patients. Abeta is formed from the progressive cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase. Two Abeta peptides are formed from APP degradation.

Gene Wiki entry for APP Gene

Additional gene information for APP Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for APP Gene

Genomics for APP Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for APP Gene

Promoters and enhancers for APP Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH21J026166 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 655.4 +2.3 2312 5.3 PKNOX1 FOXA2 ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 ZNF213 APP GC21M026165 ADAMTS5 GABPA RNU6-926P ENSG00000233783 ENSG00000273492 ENSG00000224541
GH21J026171 Enhancer 0.4 FANTOM5 dbSUPER 653.8 -0.7 -671 0.2 APP ENSG00000273492 ENSG00000233783 ENSG00000224541 GC21P026191
GH21J026138 Enhancer 1.3 Ensembl ENCODE dbSUPER 20.5 +31.1 31144 3.3 FOXA2 FEZF1 FOS ATF7 RXRA ZNF662 REST ZNF491 ATF4 ZNF610 GABPA APP ADAMTS5 ENSG00000224541 GC21P025992
GH21J026115 Enhancer 1.1 Ensembl ENCODE dbSUPER 19.8 +54.4 54359 3 NFIB CTBP1 GATA3 RCOR1 RUNX3 SMARCE1 RFX1 JUNB DPF2 ZNF217 APP ENSG00000224541 RNU6-926P ENSG00000233783 GC21P025992
GH21J026123 Enhancer 1.1 Ensembl ENCODE dbSUPER 19.6 +46.0 46021 3.4 PKNOX1 MZF1 FEZF1 GATA3 ZNF366 ZSCAN5C PRDM10 RCOR1 ZNF600 TCF7L2 APP ENSG00000224541 RNU6-926P GC21P025992
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around APP on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the APP gene promoter:
  • TBP

Genomic Locations for APP Gene

Genomic Locations for APP Gene
chr21:25,880,550-26,171,128
(GRCh38/hg38)
Size:
290,579 bases
Orientation:
Minus strand
chr21:27,252,861-27,543,446
(GRCh37/hg19)
Size:
290,586 bases
Orientation:
Minus strand

Genomic View for APP Gene

Genes around APP on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for APP Gene

Proteins for APP Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

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

    Protein Symbol:
    P05067-A4_HUMAN
    Recommended name:
    Amyloid-beta A4 protein
    Protein Accession:
    P05067
    Secondary Accessions:
    • B2R5V1
    • B4DII8
    • D3DSD1
    • D3DSD2
    • D3DSD3
    • P09000
    • P78438
    • Q13764
    • Q13778
    • Q13793
    • Q16011
    • Q16014
    • Q16019
    • Q16020
    • Q6GSC0
    • Q8WZ99
    • Q9BT38
    • Q9UC33
    • Q9UCA9
    • Q9UCB6
    • Q9UCC8
    • Q9UCD1
    • Q9UQ58

    Protein attributes for APP Gene

    Size:
    770 amino acids
    Molecular mass:
    86943 Da
    Quaternary structure:
    • Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity). Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, FPRL1, APPBP1, IB1, KNS2 (via its TPR domains) (By similarity), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1. Amyloid-beta protein 42 binds CHRNA7 in hippocampal neurons. Amyloid-beta associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Interacts with CPEB1 and AGER (By similarity). Interacts with ANKS1B and TNFRSF21. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; this is promoted by heparin binding. Amyloid-beta protein 40 interacts with S100A9. CTF-alpha product of APP interacts with GSAP. Interacts with SORL1. Interacts with PLD3. Interacts with VDAC1 (PubMed:25168729). Interacts with NSG1; could regulate APP processing (By similarity).
    Miscellaneous:
    • Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between amyloid-beta molecules resulting in amyloid-beta-metal aggregates. The affinity for copper is much higher than for other transient metals and is increased under acidic conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding.
    SequenceCaution:
    • Sequence=AAA58727.1; Type=Miscellaneous discrepancy; Note=Contamination by an Alu repeat.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for APP Gene

    Alternative splice isoforms for APP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for APP Gene

Protein Expression for APP Gene

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

Post-translational modifications for APP Gene

  • Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686.
  • Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-6, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides.
  • N- and O-glycosylated. O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate.
  • Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific. Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins. Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta. The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members. Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin.
  • Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of hydrogen peroxide results in an increased production of amyloid-beta-containing peptides.
  • Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).
  • Amyloid-beta peptides are degraded by IDE.
  • Glycosylation at posLast=697697, Ser679, Ser667, posLast=663663, posLast=659659, posLast=656656, Thr652, posLast=651651, posLast=633633, posLast=628628, posLast=623623, Ser614, Thr600, Asn571, posLast=542542, Thr381, Thr371, Thr366, posLast=352352, and Thr107
  • Ubiquitination at posLast=763763 and Lys751
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • A4_HUMAN (49)

Other Protein References for APP Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for APP Gene

Domains & Families for APP Gene

Gene Families for APP Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Transporters

Protein Domains for APP Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for APP Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P05067

UniProtKB/Swiss-Prot:

A4_HUMAN :
  • The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.
  • Belongs to the APP family.
Domain:
  • The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.
  • The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The NPXY site is also involved in clathrin-mediated endocytosis.
Family:
  • Belongs to the APP family.
genes like me logo Genes that share domains with APP: view

Function for APP Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for APP Gene

UniProtKB/Swiss-Prot Function:
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.
UniProtKB/Swiss-Prot Function:
Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.
UniProtKB/Swiss-Prot Function:
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.
UniProtKB/Swiss-Prot Function:
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
UniProtKB/Swiss-Prot Function:
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
UniProtKB/Swiss-Prot Induction:
Increased levels during neuronal differentiation.
GENATLAS Biochemistry:
amyloid beta (A4) precursor protein (APP 695) undergoing proteolytic cleavages by either alpha,beta or gamma secretases in or near the transmembrane domain,to yield several secreted derivatives,including soluble APP,4kDa,beta peptide (A beta) and a related,3 kDa,protein,expressed ubiquitously by neuronal and non neuronal cells and sorted to axons in neurons and the basolateral surface in epithelial cells (see PN2)

Gene Ontology (GO) - Molecular Function for APP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding ISS --
GO:0004867 serine-type endopeptidase inhibitor activity IDA,IEA 10652580
GO:0005102 signaling receptor binding IPI 19849849
GO:0005515 protein binding IPI 2119582
GO:0008201 heparin binding IEA --
genes like me logo Genes that share ontologies with APP: view
genes like me logo Genes that share phenotypes with APP: view

Human Phenotype Ontology for APP Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for APP Gene

MGI Knock Outs for APP:
  • App App<tm1Dbo>
  • App App<tm1b(KOMP)Wtsi>
  • App App<tm1Cwe>
  • App App<tm1.2Zhe>
  • App App<tm1.2Tlyp>
  • App App<tm2Cwe>
  • App App<tm2Umu>
  • App App<tm3.2Umu>
  • App App<tm1Somm>

Animal Model Products

miRNA for APP Gene

miRTarBase miRNAs that target APP

Clone Products

  • Addgene plasmids for APP

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for APP Gene

Localization for APP Gene

Subcellular locations from UniProtKB/Swiss-Prot for APP Gene

Membrane; Single-pass type I membrane protein. Membrane, clathrin-coated pit. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Amyloid-beta protein 42 associates with FRPL1 at the cell surface and the complex is then rapidly internalized. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions.

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 APP gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 5
endoplasmic reticulum 5
cytosol 5
golgi apparatus 5
endosome 5
cytoskeleton 4
lysosome 3
mitochondrion 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for APP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA 23921129
GO:0005641 nuclear envelope lumen IDA 21989385
GO:0005737 cytoplasm ISS --
GO:0005768 endosome IDA 18353773
genes like me logo Genes that share ontologies with APP: view

Pathways & Interactions for APP Gene

SuperPathways for APP Gene

PathCards logo More details on SuperPathways for APP
SuperPathway Contained pathways
1 Activated TLR4 signalling
Toll Like Receptor 9 (TLR9) Cascade
.94
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
.94
Activated TLR4 signalling
.91
Toll Like Receptor 4 (TLR4) Cascade
.91
MyD88 cascade initiated on plasma membrane
.88
Toll Like Receptor 10 (TLR10) Cascade
.88
Toll Like Receptor 5 (TLR5) Cascade
.88
MyD88 dependent cascade initiated on endosome
.86
Toll Like Receptor 7/8 (TLR7/8) Cascade
.86
MyD88-independent TLR3/TLR4 cascade
.86
Toll Like Receptor 3 (TLR3) Cascade
.86
TRIF-mediated TLR3/TLR4 signaling
.86
MyD88-Mal cascade initiated on plasma membrane
.85
Toll Like Receptor 2 (TLR2) Cascade
.85
Toll Like Receptor TLR1-TLR2 Cascade
.85
Toll Like Receptor TLR6-TLR2 Cascade
.85
Toll-Like Receptors Cascades
.82
2 Cytosolic sensors of pathogen-associated DNA
RIP-mediated NFkB activation via ZBP1
.84
ZBP1(DAI) mediated induction of type I IFNs
.84
TRAF6 mediated NF-kB activation
.53
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
.47
Cytosolic sensors of pathogen-associated DNA
.36
DEx/H-box helicases activate type I IFN and inflammatory cytokines production
.01
3 Peptide ligand-binding receptors
Class A/1 (Rhodopsin-like receptors)
.71
GPCR ligand binding
.71
Peptide ligand-binding receptors
.58
G alpha (i) signalling events
.42
Formyl peptide receptors bind formyl peptides and many other ligands
.01
4 Response to elevated platelet cytosolic Ca2+
Platelet activation, signaling and aggregation
.49
Response to elevated platelet cytosolic Ca2+
.49
Platelet degranulation
.47
Hemostasis
.44
5 Clathrin derived vesicle budding
Clathrin derived vesicle budding
.78
trans-Golgi Network Vesicle Budding
.78
Lysosome Vesicle Biogenesis
.49
genes like me logo Genes that share pathways with APP: view

SIGNOR curated interactions for APP Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for APP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001934 positive regulation of protein phosphorylation IGI 15457210
GO:0001967 suckling behavior IEA --
GO:0002265 astrocyte activation involved in immune response IGI 23152628
GO:0002576 platelet degranulation TAS --
GO:0006378 mRNA polyadenylation ISS --
genes like me logo Genes that share ontologies with APP: view

Drugs & Compounds for APP Gene

Products:

  1. Drug

(135) Drugs for APP Gene - From: DrugBank, ApexBio, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma Target, aggregation inhibitor 202
Dimercaprol Approved Pharma Target 0
Aluminium Approved, Investigational Pharma Target 0
Deferoxamine Approved, Investigational Pharma Target 47
Florbetaben (18F) Approved Pharma Target, binder 0

(52) Additional Compounds for APP Gene - From: Novoseek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
EGCG
989-51-5
Fe2+
  • FE (II) ion
  • Fe(II)
  • Fe(2+)
  • Ferrous ion
  • Iron ion(2+)
 15438-31-0
Dimebon dihydrochloride
97657-92-6
NQTrp
185351-19-3
SEN 1269
956128-01-1

(5) Tocris Compounds for APP Gene

Compound Action Cas Number
Dimebon dihydrochloride Neuroprotectant; protects against beta-amyloid neurotoxicity 97657-92-6
EGCG Inhibits formation of amyloid fibrils 989-51-5
NQTrp Potent inhibitor of Abeta oligomer and fibril formation 185351-19-3
Ro 90-7501 Inhibitor of Abeta42 fibril formation 293762-45-5
SEN 1269 Amyloid-beta aggregation inhibitor 956128-01-1
genes like me logo Genes that share compounds with APP: view

Drug Products

Transcripts for APP Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for APP Gene

(11) REFSEQ mRNAs :
(28) Additional mRNA sequences :
(1024) Selected AceView cDNA sequences:
(17) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for APP Gene

Amyloid beta (A4) precursor protein:
Representative Sequences:

Clone Products

  • Addgene plasmids for APP

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

No ASD Table

Relevant External Links for APP Gene

GeneLoc Exon Structure for
APP
ECgene alternative splicing isoforms for
APP

Expression for APP Gene

Products:

  1. Primer
  2. Gene Expression Assay

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

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

Protein differential expression in normal tissues from HIPED for APP Gene

This gene is overexpressed in Amniocyte (33.7), Cerebrospinal fluid (11.3), and Serum (7.2).

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



Protein tissue co-expression partners for APP Gene

NURSA nuclear receptor signaling pathways regulating expression of APP Gene:

APP

SOURCE GeneReport for Unigene cluster for APP Gene:

Hs.434980

mRNA Expression by UniProt/SwissProt for APP Gene:

P05067-A4_HUMAN
Tissue specificity: Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex-opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra-striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non-neuronal cells. Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes.

Evidence on tissue expression from TISSUES for APP Gene

  • Nervous system(5)
  • Eye(4.9)
  • Pancreas(4.9)
  • Intestine(4.7)
  • Blood(4.6)
  • Liver(4.6)
  • Bone marrow(4.5)
  • Kidney(4.4)
  • Lung(4.4)
  • Thyroid gland(4.2)
  • Skin(3.6)
  • Adrenal gland(3.5)
  • Lymph node(3.2)
  • Muscle(3.2)
  • Heart(3.1)
  • Stomach(3)
  • Spleen(2.9)
  • Gall bladder(2.4)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cerebellum
  • ear
  • head
  • mouth
  • pharynx
Thorax:
  • esophagus
  • heart
Abdomen:
  • stomach
Limb:
  • foot
  • lower limb
  • upper limb
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with APP: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for APP Gene

Orthologs for APP Gene

This gene was present in the common ancestor of animals.

Orthologs for APP Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia APP 34 33
  • 99.7 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia APP 34 33
  • 91.22 (n)
 OneToOne
dog
(Canis familiaris)
 Mammalia APP 34 33
  • 91.17 (n)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia APP 34
  • 91 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia App 16 34 33
  • 89.36 (n)
rat
(Rattus norvegicus)
 Mammalia App 33
  • 89.27 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia APP 34
  • 70 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves APP 34 33
  • 82.54 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia APP 34
  • 70 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia app 33
  • 78.76 (n)
Str.11113 33
African clawed frog
(Xenopus laevis)
 Amphibia MGC52816 33
zebrafish
(Danio rerio)
 Actinopterygii appb 34 33
  • 69.02 (n)
 OneToMany
appa 34
  • 69 (a)
 OneToMany
APP (1 of 3) 34
  • 62 (a)
 OneToMany
-- 33
fruit fly
(Drosophila melanogaster)
 Insecta Appl 34
  • 20 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea apl-1 34 35 33
  • 45.96 (n)
 OneToMany
Species where no ortholog for APP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for APP Gene

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

Paralogs for APP Gene

Paralogs for APP Gene

(6) SIMAP similar genes for APP Gene using alignment to 10 proteins:

  • A4_HUMAN
  • E9PEV0_HUMAN
  • E9PG40_HUMAN
  • H7C0V9_HUMAN
  • H7C104_HUMAN
  • H7C2L2_HUMAN
  • L7XCZ9_HUMAN
  • L7XE61_HUMAN
  • L8EC46_HUMAN
  • Q9BYY9_HUMAN
genes like me logo Genes that share paralogs with APP: view

Variants for APP Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for APP Gene

SNP ID Clin Chr 21 pos Variation AA Info Type
rs112263157 likely-benign, Early-Onset Familial Alzheimer Disease 25,911,810(-) T/C coding_sequence_variant, missense_variant
rs114675472 likely-benign, Early-Onset Familial Alzheimer Disease 25,975,945(-) A/C/G intron_variant
rs116650065 likely-benign, Early-Onset Familial Alzheimer Disease 25,891,800(-) G/T coding_sequence_variant, synonymous_variant
rs137865262 uncertain-significance, Early-Onset Familial Alzheimer Disease 25,911,961(-) A/G coding_sequence_variant, synonymous_variant
rs145081708 uncertain-significance, conflicting-interpretations-of-pathogenicity, Early-Onset Familial Alzheimer Disease, not specified 26,051,070(-) A/G coding_sequence_variant, missense_variant

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

Variant ID Type Subtype PubMed ID
dgv2372n106 CNV deletion 24896259
dgv2373n106 OTHER inversion 24896259
esv1301961 OTHER inversion 17803354
esv2648254 OTHER inversion 19546169
esv2660354 CNV deletion 23128226
esv2723294 CNV deletion 23290073
esv2723296 CNV deletion 23290073
esv2723297 CNV deletion 23290073
esv2965 OTHER inversion 18987735
esv3328188 OTHER inversion 20981092
esv3365040 OTHER inversion 20981092
esv3557581 CNV deletion 23714750
esv3568139 CNV loss 25503493
esv3568140 CNV loss 25503493
esv3575384 CNV gain 25503493
esv3646725 CNV loss 21293372
esv3646726 CNV loss 21293372
esv3646727 OTHER inversion 21293372
esv3646728 CNV loss 21293372
esv4736 CNV loss 18987735
esv7875 OTHER inversion 19470904
esv998808 OTHER inversion 20482838
nsv1078317 OTHER inversion 25765185
nsv1114275 CNV deletion 24896259
nsv1114276 CNV deletion 24896259
nsv1114277 CNV deletion 24896259
nsv1114278 CNV deletion 24896259
nsv1114279 CNV deletion 24896259
nsv1123543 CNV deletion 24896259
nsv1123544 CNV deletion 24896259
nsv1123545 CNV deletion 24896259
nsv1136617 CNV deletion 24896259
nsv1146320 CNV duplication 26484159
nsv1148130 OTHER inversion 26484159
nsv510502 OTHER sequence alteration 20534489
nsv513715 OTHER inversion 21212237
nsv513716 OTHER inversion 21212237
nsv526774 CNV loss 19592680

Variation tolerance for APP Gene

Residual Variation Intolerance Score: 5.89% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.13; 38.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for APP Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for APP Gene

MalaCards: The human disease database

(60) MalaCards diseases for APP Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
cerebral amyloid angiopathy, app-related
  • amyloidosis, cerebroarterial, app-related
alzheimer disease
  • ad
alzheimer disease type 1
  • ad1
early-onset, autosomal dominant alzheimer disease
  • early-onset autosomal dominant alzheimer disease
early-onset familial alzheimer disease
  • eofad
- elite association - COSMIC cancer census association via MalaCards
Search APP in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

A4_HUMAN
  • Alzheimer disease 1 (AD1) [MIM:104300]: A familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. 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:10097173, ECO:0000269 PubMed:10631141, ECO:0000269 PubMed:10665499, ECO:0000269 PubMed:10867787, ECO:0000269 PubMed:11063718, ECO:0000269 PubMed:11311152, ECO:0000269 PubMed:11528419, ECO:0000269 PubMed:12034808, ECO:0000269 PubMed:1302033, ECO:0000269 PubMed:1303239, ECO:0000269 PubMed:1303275, ECO:0000269 PubMed:1415269, ECO:0000269 PubMed:15201367, ECO:0000269 PubMed:15365148, ECO:0000269 PubMed:15668448, ECO:0000269 PubMed:1671712, ECO:0000269 PubMed:1678058, ECO:0000269 PubMed:1908231, ECO:0000269 PubMed:1925564, ECO:0000269 PubMed:1944558, ECO:0000269 PubMed:8267572, ECO:0000269 PubMed:8290042, ECO:0000269 PubMed:8476439, ECO:0000269 PubMed:8577393, ECO:0000269 PubMed:9328472, ECO:0000269 PubMed:9754958}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cerebral amyloid angiopathy, APP-related (CAA-APP) [MIM:605714]: A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. {ECO:0000269 PubMed:11409420, ECO:0000269 PubMed:12654973, ECO:0000269 PubMed:16178030, ECO:0000269 PubMed:20697050, ECO:0000269 PubMed:2111584}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for APP

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

No data available for Genatlas for APP Gene

Publications for APP Gene

  1. Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP. (PMID: 20697050) Bugiani O … Tagliavini F (Archives of neurology 2010) 3 4 44 58
  2. Association studies testing for risk for late-onset Alzheimer's disease with common variants in the beta-amyloid precursor protein (APP). (PMID: 17427190) Nowotny P … Goate A (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2007) 3 22 44 58
  3. Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein. (PMID: 11784781) White AR … Cappai R (The Journal of neuroscience : the official journal of the Society for Neuroscience 2002) 3 4 22 58
  4. Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. (PMID: 11517218) Ando K … Suzuki T (The Journal of biological chemistry 2001) 3 4 22 58
  5. Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease. (PMID: 11438549) Scheuermann S … Multhaup G (The Journal of biological chemistry 2001) 3 4 22 58

Products for APP Gene