APP
amyloid beta precursor protein | alpha-sAPP, AD1

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]

Member of: DE-3 DE-3.33
Biological processes 310 terms
DNA binding (GO:0003677)G protein-coupled receptor binding (GO:0001664)G protein-coupled receptor signaling pathway (GO:0007186)G protein-coupled receptor signaling pathway (GO:0007186)Golgi apparatus (GO:0005794)Golgi apparatus (GO:0005794)Golgi apparatus (GO:0005794)Golgi apparatus (GO:0005794)Golgi lumen (GO:0005796)Golgi-associated vesicle (GO:0005798)NMDA selective glutamate receptor signaling pathway (GO:0098989)PTB domain binding (GO:0051425)RAGE receptor binding (GO:0050786)acetylcholine receptor activator activity (GO:0030549)acetylcholine receptor binding (GO:0033130)adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189)adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193)adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193)adult locomotory behavior (GO:0008344)amylin binding (GO:0097645)amyloid fibril formation (GO:1990000)amyloid fibril formation (GO:1990000)amyloid-beta complex (GO:0106003)amyloid-beta complex (GO:0106003)amyloid-beta complex (GO:0106003)amyloid-beta complex (GO:0106003)antibacterial humoral response (GO:0019731)antifungal humoral response (GO:0019732)antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844)apolipoprotein binding (GO:0034185)associative learning (GO:0008306)astrocyte activation (GO:0048143)astrocyte activation (GO:0048143)astrocyte activation involved in immune response (GO:0002265)astrocyte projection (GO:0097449)axo-dendritic transport (GO:0008088)axon (GO:0030424)axon (GO:0030424)axon midline choice point recognition (GO:0016199)axonogenesis (GO:0007409)axonogenesis (GO:0007409)calcium ion transport (GO:0006816)calcium-mediated signaling (GO:0019722)calcium-mediated signaling (GO:0019722)cell body (GO:0044297)cell surface (GO:0009986)cell surface (GO:0009986)cell surface (GO:0009986)cell surface (GO:0009986)cellular response to amyloid-beta (GO:1904646)cellular response to amyloid-beta (GO:1904646)cellular response to cAMP (GO:0071320)cellular response to copper ion (GO:0071280)cellular response to manganese ion (GO:0071287)cellular response to nerve growth factor stimulus (GO:1990090)cellular response to norepinephrine stimulus (GO:0071874)central nervous system development (GO:0007417)chemical synaptic transmission (GO:0007268)chemoattractant activity (GO:0042056)chromatin binding (GO:0003682)clathrin-coated pit (GO:0005905)cognition (GO:0050890)collateral sprouting in absence of injury (GO:0048669)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasmic vesicle (GO:0031410)cytosol (GO:0005829)defense response to Gram-negative bacterium (GO:0050829)defense response to Gram-positive bacterium (GO:0050830)dendrite (GO:0030425)dendrite (GO:0030425)dendrite development (GO:0016358)dendrite membrane (GO:0032590)dendrite membrane (GO:0032590)dendritic shaft (GO:0043198)dendritic spine (GO:0043197)early endosome (GO:0005769)early endosome (GO:0005769)early endosome (GO:0005769)early endosome (GO:0005769)early endosome membrane (GO:0031901)endocytosis (GO:0006897)endoplasmic reticulum (GO:0005783)endoplasmic reticulum (GO:0005783)endoplasmic reticulum lumen (GO:0005788)endosome (GO:0005768)endosome lumen (GO:0031904)endosome to plasma membrane transport vesicle (GO:0070381)enzyme binding (GO:0019899)ephrin receptor binding (GO:0046875)external side of plasma membrane (GO:0009897)extracellular exosome (GO:0070062)extracellular matrix organization (GO:0030198)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)frizzled binding (GO:0005109)growth cone (GO:0030426)growth cone filopodium (GO:1990812)growth cone lamellipodium (GO:1990761)growth factor receptor binding (GO:0070851)heparan sulfate binding (GO:1904399)heparan sulfate proteoglycan binding (GO:0043395)heparin binding (GO:0008201)high-density lipoprotein particle (GO:0034364)high-density lipoprotein particle (GO:0034364)hippocampal neuron apoptotic process (GO:0110088)identical protein binding (GO:0042802)innate immune response (GO:0045087)insulin receptor binding (GO:0005158)integrin binding (GO:0005178)intermediate-density lipoprotein particle (GO:0034363)intermediate-density lipoprotein particle (GO:0034363)intracellular copper ion homeostasis (GO:0006878)ionotropic glutamate receptor signaling pathway (GO:0035235)learning (GO:0007612)learning or memory (GO:0007611)learning or memory (GO:0007611)learning or memory (GO:0007611)lipoprotein metabolic process (GO:0042157)lipoprotein particle (GO:1990777)locomotory behavior (GO:0007626)low-density lipoprotein particle (GO:0034362)low-density lipoprotein particle mediated signaling (GO:0055096)low-density lipoprotein particle receptor binding (GO:0050750)lysosome (GO:0005764)main axon (GO:0044304)mating behavior (GO:0007617)membrane (GO:0016020)membrane (GO:0016020)membrane raft (GO:0045121)membrane raft (GO:0045121)memory (GO:0007613)microglia development (GO:0014005)microglial cell activation (GO:0001774)microglial cell activation (GO:0001774)mitochondrial inner membrane (GO:0005743)mitochondrion (GO:0005739)modulation of excitatory postsynaptic potential (GO:0098815)molecular function activator activity (GO:0140677)negative regulation of Wnt signaling pathway (GO:0030178)negative regulation of amyloid-beta formation (GO:1902430)negative regulation of blood circulation (GO:1903523)negative regulation of canonical Wnt signaling pathway (GO:0090090)negative regulation of cell population proliferation (GO:0008285)negative regulation of dendritic spine maintenance (GO:1902951)negative regulation of dendritic spine maintenance (GO:1902951)negative regulation of gene expression (GO:0010629)negative regulation of gene expression (GO:0010629)negative regulation of gene expression (GO:0010629)negative regulation of long-term synaptic potentiation (GO:1900272)negative regulation of long-term synaptic potentiation (GO:1900272)negative regulation of long-term synaptic potentiation (GO:1900272)negative regulation of miRNA transcription (GO:1902894)negative regulation of protein localization to nucleus (GO:1900181)negative regulation of transcription by RNA polymerase II (GO:0000122)neuron projection (GO:0043005)neuron projection (GO:0043005)neuron projection development (GO:0031175)neuron projection development (GO:0031175)neuron projection maintenance (GO:1990535)neuron remodeling (GO:0016322)neuronal dense core vesicle (GO:0098992)nuclear envelope lumen (GO:0005641)nucleus (GO:0005634)nucleus (GO:0005634)peptidase activator activity (GO:0016504)peptidase inhibitor activity (GO:0030414)perikaryon (GO:0043204)perinuclear region of cytoplasm (GO:0048471)phospholipase D-activating G protein-coupled receptor signaling pathway (GO:0031583)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)platelet alpha granule (GO:0031091)platelet alpha granule lumen (GO:0031093)positive chemotaxis (GO:0050918)positive regulation of ERK1 and ERK2 cascade (GO:0070374)positive regulation of ERK1 and ERK2 cascade (GO:0070374)positive regulation of ERK1 and ERK2 cascade (GO:0070374)positive regulation of G protein-coupled receptor internalization (GO:1904022)positive regulation of G protein-coupled receptor signaling pathway (GO:0045745)positive regulation of JNK cascade (GO:0046330)positive regulation of MAPK cascade (GO:0043410)positive regulation of MAPK cascade (GO:0043410)positive regulation of MAPK cascade (GO:0043410)positive regulation of T cell migration (GO:2000406)positive regulation of Toll signaling pathway (GO:0045752)positive regulation of amyloid fibril formation (GO:1905908)positive regulation of amyloid precursor protein catabolic process (GO:1902993)positive regulation of apoptotic process (GO:0043065)positive regulation of apoptotic process (GO:0043065)positive regulation of apoptotic process (GO:0043065)positive regulation of apoptotic process (GO:0043065)positive regulation of cAMP/PKA signal transduction (GO:0141163)positive regulation of calcium-mediated signaling (GO:0050850)positive regulation of cell activation (GO:0050867)positive regulation of chemokine production (GO:0032722)positive regulation of endothelin production (GO:1904472)positive regulation of excitatory postsynaptic potential (GO:2000463)positive regulation of extrinsic apoptotic signaling pathway (GO:2001238)positive regulation of gene expression (GO:0010628)positive regulation of gene expression (GO:0010628)positive regulation of gene expression (GO:0010628)positive regulation of gene expression (GO:0010628)positive regulation of gene expression, epigenetic (GO:0141137)positive regulation of glycolytic process (GO:0045821)positive regulation of inflammatory response (GO:0050729)positive regulation of interleukin-1 beta production (GO:0032731)positive regulation of interleukin-6 production (GO:0032755)positive regulation of long-term synaptic depression (GO:1900454)positive regulation of long-term synaptic depression (GO:1900454)positive regulation of long-term synaptic potentiation (GO:1900273)positive regulation of membrane protein ectodomain proteolysis (GO:0051044)positive regulation of membrane protein ectodomain proteolysis (GO:0051044)positive regulation of mitotic cell cycle (GO:0045931)positive regulation of monocyte chemotaxis (GO:0090026)positive regulation of monocyte chemotaxis (GO:0090026)positive regulation of neuron apoptotic process (GO:0043525)positive regulation of neuron apoptotic process (GO:0043525)positive regulation of neuron differentiation (GO:0045666)positive regulation of neuron differentiation (GO:0045666)positive regulation of nitric oxide biosynthetic process (GO:0045429)positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224)positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)positive regulation of protein import (GO:1904591)positive regulation of protein metabolic process (GO:0051247)positive regulation of protein metabolic process (GO:0051247)positive regulation of protein metabolic process (GO:0051247)positive regulation of protein metabolic process (GO:0051247)positive regulation of response to endoplasmic reticulum stress (GO:1905898)positive regulation of superoxide anion generation (GO:0032930)positive regulation of synaptic transmission, cholinergic (GO:0032224)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of tumor necrosis factor production (GO:0032760)positive regulation of type II interferon production (GO:0032729)postsynapse (GO:0098794)presynapse (GO:0098793)protein binding (GO:0005515)protein heterodimerization activity (GO:0046982)protein homodimerization activity (GO:0042803)protein homooligomerization (GO:0051260)protein serine/threonine kinase binding (GO:0120283)protein tetramerization (GO:0051262)protein tetramerization (GO:0051262)protein trimerization (GO:0070206)protein trimerization (GO:0070206)protein-containing complex (GO:0032991)protein-containing complex (GO:0032991)protein-folding chaperone binding (GO:0051087)receptor ligand activity (GO:0048018)receptor ligand activity (GO:0048018)recycling endosome (GO:0055037)regulation of MAPK cascade (GO:0043408)regulation of Wnt signaling pathway (GO:0030111)regulation of amyloid fibril formation (GO:1905906)regulation of amyloid-beta clearance (GO:1900221)regulation of calcium ion transmembrane transport via high voltage-gated calcium channel (GO:1902514)regulation of dendritic spine maintenance (GO:1902950)regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway (GO:1903381)regulation of gene expression (GO:0010468)regulation of gene expression (GO:0010468)regulation of long-term neuronal synaptic plasticity (GO:0048169)regulation of multicellular organism growth (GO:0040014)regulation of neuron apoptotic process (GO:0043523)regulation of neurotransmitter uptake (GO:0051580)regulation of presynapse assembly (GO:1905606)regulation of presynapse assembly (GO:1905606)regulation of protein metabolic process (GO:0051246)regulation of response to calcium ion (GO:1905945)regulation of spontaneous synaptic transmission (GO:0150003)regulation of synapse structure or activity (GO:0050803)regulation of toll-like receptor signaling pathway (GO:0034121)regulation of transcription by RNA polymerase II (GO:0006357)regulation of translation (GO:0006417)response to auditory stimulus (GO:0010996)response to ethanol (GO:0045471)response to insulin-like growth factor stimulus (GO:1990418)response to interleukin-1 (GO:0070555)response to interleukin-1 (GO:0070555)response to lead ion (GO:0010288)response to yeast (GO:0001878)serine-type endopeptidase inhibitor activity (GO:0004867)serine-type endopeptidase inhibitor activity (GO:0004867)signaling receptor activator activity (GO:0030546)signaling receptor activator activity (GO:0030546)signaling receptor binding (GO:0005102)signaling receptor binding (GO:0005102)signaling receptor complex (GO:0043235)swimming behavior (GO:0036269)synapse (GO:0045202)synapse organization (GO:0050808)synaptic cleft (GO:0043083)synaptic membrane (GO:0097060)trans-Golgi network membrane (GO:0032588)transition metal ion binding (GO:0046914)very-low-density lipoprotein particle (GO:0034361)visual learning (GO:0008542)
Expression (TPM)
APP — as a Regulated Gene

TFs regulating APP 0 TFs

Transcription factors with Perturb-seq knockdown data for APP. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = APP upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to APP

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of APP, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr21:25,801,218–25,801,857 369.1 kb Distal (>10kb) Multiome 381
chr21:25,997,730–25,998,922 172.4 kb Distal (>10kb) Multiome 297
chr21:26,169,141–26,171,427 24 bp At TSS Multiome 747

Genome Browser

Genomic view of the APP locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr21:25,791,218 – 26,181,427
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq