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This gene encodes a multi-pass transmembrane protein that is a functional component of the gamma-secretase complex, which also contains presenilin and nicastrin. This protein represents a stabilizing cofactor for the presenilin holoprotein in the complex. The gamma-secretase complex catalyzes the cleavage of integral proteins such as notch receptors and beta-amyloid precursor p... See more...
Aliases for APH1B Gene
Aliases for APH1B Gene
External Ids for APH1B Gene
- HGNC: 24080
- Entrez Gene: 83464
- Ensembl: ENSG00000138613
- OMIM: 607630
- UniProtKB: Q8WW43
Previous GeneCards Identifiers for APH1B Gene
- GC15P061357
- GC15P063569
- GC15P040392
- GC15P063647
- GC15P064360
- GC15P064873
- GC15P065755
- GC15P063467
- GC15P063778
- GC15P069507
- GC15P069615
- GC15P069677
- GC15P071873
- GC15P064282
- GC15P066328
- GC15P066882
- GC15P067411
- GC15P067937
- GC15P068426
- GC15P068936
- GC15P069397
Summaries for APH1B Gene
-
This gene encodes a multi-pass transmembrane protein that is a functional component of the gamma-secretase complex, which also contains presenilin and nicastrin. This protein represents a stabilizing cofactor for the presenilin holoprotein in the complex. The gamma-secretase complex catalyzes the cleavage of integral proteins such as notch receptors and beta-amyloid precursor protein. [provided by RefSeq, Sep 2011]
GeneCards Summary for APH1B Gene
APH1B (Aph-1 Homolog B, Gamma-Secretase Subunit) is a Protein Coding gene. Diseases associated with APH1B include Alzheimer Disease and Aortic Valve Disease 1. Among its related pathways are Signaling by GPCR and Development NOTCH1-mediated pathway for NF-KB activity modulation. Gene Ontology (GO) annotations related to this gene include peptidase activity. An important paralog of this gene is APH1A.
UniProtKB/Swiss-Prot Summary for APH1B Gene
-
Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A.
Additional gene information for APH1B Gene
- HGNC(24080)
- Entrez Gene(83464)
- Ensembl(ENSG00000138613)
- OMIM(607630)
- UniProtKB(Q8WW43)
- Open Targets Platform(ENSG00000138613)
- Monarch Initiative
- Search for APH1B at DataMed
- Search for APH1B at HumanCyc
No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for APH1B Gene
Genomics for APH1B Gene
GeneHancer (GH) Regulatory Elements Pubs
Promoters and enhancers for APH1B 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 APH1B on the GeneHancer Hub at the UCSC Golden Path
Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for APH1B
- Top Transcription factor binding sites by QIAGEN in the APH1B gene promoter:
-
- AML1a
- FOXF2
- GATA-3
- HNF-3beta
- IRF-1
- LCR-F1
- Nkx2-5
- p53
- SRY
Genomic Locations for APH1B Gene
Genomic Locations for APH1B Gene
- chr15:63,276,018-63,309,126
- (GRCh38/hg38)
- Size:
- 33,109 bases
- Orientation:
- Plus strand
- chr15:63,568,217-63,601,325
- (GRCh37/hg19)
- Size:
- 33,109 bases
- Orientation:
- Plus strand
Genomic View for APH1B Gene
Genes around APH1B on UCSC Golden Path with GeneCards custom track
- Cytogenetic band:
-
- 15q22.2 by HGNC
- 15q22.2 by Entrez Gene
- 15q22.2 by Ensembl
APH1B Gene in genomic location: bands according to
Ensembl, locations according to GeneLoc
(and/or Entrez Gene and/or Ensembl if different)
Genomic Neighborhood
• Exon Structure
• Gene Density
RefSeq DNA sequence for APH1B Gene
Proteins for APH1B Gene
-
Protein details for APH1B Gene (UniProtKB/Swiss-Prot)
- Protein Symbol:
- Q8WW43-APH1B_HUMAN
- Recommended name:
- Gamma-secretase subunit APH-1B
- Protein Accession:
- Q8WW43
- A8K589
- Q564N3
- Q6UWQ1
- Q9H0S0
Protein attributes for APH1B Gene
- Size:
- 257 amino acids
- Molecular mass:
- 28460 Da
- Quaternary structure:
-
- Probable component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist (By similarity). Interacts with PSEN1 and PSEN2.
- Miscellaneous:
-
- [Isoform 2]: Expressed at low levels in most tissues.
Protein Expression for APH1B Gene
Post-translational modifications for APH1B Gene
Other Protein References for APH1B Gene
- ENSEMBL proteins:
- REFSEQ proteins:
Antibody Products
- Creative Diagnostics Anti-APH1B monoclonal antibody
- Creative Biolabs Recombinant Anti-human APH1B VHH Single Domain Antibody
-
Custom Antibody ServicesOriGene Antibodies for APH1B
- Novus Biologicals Antibodies for APH1B
-
Abcam antibodies for APH1B
- Invitrogen Antibodies for APH1B (AFLGC-APH1B)
Protein Products
- Search Origene for Purified Proteins, MassSpec and Protein Over-expression Lysates for APH1B
- Origene Custom Protein Services for APH1B
No data available for DME Specific Peptides for APH1B Gene
Domains & Families for APH1B Gene
Gene Families for APH1B Gene
- Human Protein Atlas (HPA):
-
- Predicted membrane proteins
Suggested Antigen Peptide Sequences for APH1B Gene
- GenScript: Design optimal peptide antigens:
-
- Presenilin-stabilization factor-like (APH1B_HUMAN)
Graphical View of Domain Structure for InterPro Entry
Q8WW43- Family:
-
- Belongs to the APH-1 family.
Function for APH1B Gene
Molecular function for APH1B Gene
- UniProtKB/Swiss-Prot Function:
- Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A.
Phenotypes From GWAS Catalog for APH1B Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0004175 | endopeptidase activity | IBA | 21873635 |
| GO:0005515 | protein binding | IPI | 12297508 |
| GO:0008233 | peptidase activity | IDA | 12297508 |
Phenotypes for APH1B Gene
- MGI mutant phenotypes for APH1B:
- inferred from 1 alleles
- GenomeRNAi human phenotypes for APH1B:
Animal Models for APH1B Gene
- MGI Knock Outs for APH1B:
-
- Aph1b Aph1b<tm1Bdes>
Animal Model Products
- Taconic Biosciences: Generate A Custom CRISPR Mouse Model For Your Study
CRISPR Products
- Applied Biological Materials (abm): CRISPR Clones for APH1B - Select products 50% OFF >
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-
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-
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miRNA for APH1B Gene
- miRTarBase miRNAs that target APH1B
miRNA Products
Inhibitory RNA Products
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Clone Products
- Applied Biological Materials (abm): Clones for APH1B - Select products 50% OFF >
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- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
- Sino Biological Human cDNA Clone for APH1B
- Addgene plasmids for APH1B
- Search GeneCopoeia for ORF cDNA, lentivirus, AAV viral particles and/or promoter clone products for APH1B
Cell Line Products
-
Horizon Cell Lines for APH1B
No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for APH1B Gene
Localization for APH1B Gene
Subcellular locations from UniProtKB/Swiss-Prot for APH1B Gene
- Membrane. Multi-pass membrane protein.
| Compartment | Confidence |
|---|---|
| plasma membrane | 5 |
| endosome | 4 |
| endoplasmic reticulum | 3 |
| extracellular | 1 |
| cytoskeleton | 1 |
| mitochondrion | 1 |
| nucleus | 1 |
| cytosol | 1 |
| lysosome | 1 |
| golgi apparatus | 1 |
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0005783 | endoplasmic reticulum | IBA | 21873635 |
| GO:0005886 | plasma membrane | TAS | -- |
| GO:0005887 | integral component of plasma membrane | IBA | 21873635 |
| GO:0010008 | endosome membrane | TAS | -- |
| GO:0016020 | membrane | IEA | -- |
No data available for Subcellular locations from the Human Protein Atlas (HPA) for APH1B Gene
Pathways & Interactions for APH1B Gene
| SuperPathway | Contained pathways | ||
|---|---|---|---|
| 1 | Signaling by NOTCH1 | ||
| 2 | Notch Signaling Pathway (WikiPathways) | ||
| 3 | p75 NTR receptor-mediated signalling | ||
| 4 | NOTCH2 Activation and Transmission of Signal to the Nucleus | ||
| 5 | Developmental Biology |
.51
|
|
Pathways by source for APH1B Gene
1 Sino Biological pathway for APH1B Gene
6 BioSystems pathways for APH1B Gene
2 KEGG pathways for APH1B Gene
3 GeneGo (Thomson Reuters) pathways for APH1B Gene
- Development MAG-dependent inhibition of neurite outgrowth
- Development Notch Signaling Pathway
- Development NOTCH1-mediated pathway for NF-KB activity modulation
3 Qiagen pathways for APH1B Gene
- ErbB4 Pathway
- Molecular Mechanisms of Cancer
- Presenilin-Mediated Signaling
Interacting Proteins for APH1B Gene
Selected Interacting proteins:
Q8WW43-APH1B_HUMAN
ENSP00000261879
for APH1B Gene via
UniProtKB
STRING
IID
GPS-Prot Interaction Network for APH1B
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0007219 | Notch signaling pathway | IBA | 21873635 |
| GO:0007220 | Notch receptor processing | IBA | 21873635 |
| GO:0007626 | locomotory behavior | IEA | -- |
| GO:0016485 | protein processing | IEA,IDA | 12297508 |
| GO:0031293 | membrane protein intracellular domain proteolysis | TAS | -- |
Drugs & Compounds for APH1B Gene
| Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
|---|---|---|---|---|---|---|
| MK-0752 | Investigational | Pharma | γ-secretase inhibitor | 0 | ||
| BMS-906024 | Investigational | Pharma | inhibitor | Gamma-secretase inhibitor | 0 | |
| GSI-136 | Investigational | Pharma | 0 | |||
| BMS-708163 (Avagacestat) | Pharma | γ-secretase inhibitor | 0 | |||
| DAPT (GSI-IX) | Pharma | γ-secretase inhibitor,potent and specific | 0 |
(8) ApexBio Compounds for APH1B Gene
| Compound | Action | Cas Number |
|---|---|---|
| BMS-708163 (Avagacestat) | γ-secretase inhibitor | 1146699-66-2 |
| DAPT (GSI-IX) | γ-secretase inhibitor,potent and specific | 208255-80-5 |
| LY2811376 | Non-peptidic BACE1 inhibitor | 1194044-20-6 |
| LY-411575 | Gamma secretase inhibitor | 209984-57-6 |
| MK-0752 | γ-secretase inhibitor | 471905-41-6 |
| RO4929097 | γ secretase inhibitor | 847925-91-1 |
| Semagacestat (LY450139) | γ-secretase inhibitor | 425386-60-3 |
| YO-01027 (Dibenzazepine, DBZ) | γ-secretase inhibitor | 209984-56-5 |
Transcripts for APH1B Gene
mRNA/cDNA for APH1B Gene
- 2 REFSEQ mRNAs :
- 15 NCBI additional mRNA sequence :
- 10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :
-
- ENST00000560890 758 nts (view in UCSC)
- ENST00000559744 456 nts (view in UCSC)
- ENST00000261879 4138 nts (view in UCSC)
- ENST00000380343 685 nts (view in UCSC)
- ENST00000380340 872 nts (view in UCSC)
CRISPR Products
- Applied Biological Materials (abm): CRISPR Clones for APH1B - Select products 50% OFF >
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-
OriGene CRISPR knockouts for APH1B
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-
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miRNA Products
Inhibitory RNA Products
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Clone Products
- Applied Biological Materials (abm): Clones for APH1B - Select products 50% OFF >
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- Sino Biological Human cDNA Clone for APH1B
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| ExUns: | 1 | ^ | 2a | · | 2b | · | 2c | · | 2d | · | 2e | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6a | · | 6b | · | 6c | ^ | 7 | ^ | 8a | · | 8b | ^ | 9a | · | 9b | · | 9c | · | 9d |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SP1: | - | - | - | - | |||||||||||||||||||||||||||||||||
| SP2: | - | - | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||
| SP3: | - | - | - | - | - | ||||||||||||||||||||||||||||||||
| SP4: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||
| SP5: | - | - | - | - | - | - | |||||||||||||||||||||||||||||||
| SP6: | - | - | |||||||||||||||||||||||||||||||||||
| SP7: | - | ||||||||||||||||||||||||||||||||||||
| SP8: | - |
Relevant External Links for APH1B Gene
- GeneLoc Exon Structure for
- APH1B
Expression for APH1B Gene
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery
-
Testis (Reproductive System)
- Leydig Cells Testis Interstitium
- Seminiferous Tubules
- Testis Interstitium
-
Blood (Hematopoietic System)
- Granulocytes Peripheral Blood
- Brain (Nervous System)
mRNA differential expression in normal tissues according to GTEx for APH1B Gene
This gene is overexpressed in Testis (x5.1).
This gene is overexpressed in Testis (43.2), Peripheral blood mononuclear cells (13.5), and Spinal cord (11.9).
Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for APH1B Gene
Transcriptomic regulation report from SPP (The Signaling Pathways Project) for APH1B
SOURCE GeneReport for Unigene cluster for APH1B Gene:
Hs.511703mRNA Expression by UniProt/SwissProt for APH1B Gene:
Q8WW43-APH1B_HUMAN
Tissue specificity:
Weakly or not expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, colon, skeletal muscle, heart and brain.
Evidence on tissue expression from TISSUES for APH1B Gene
- Nervous system(4.8)
Primer Products
-
OriGene qPCR primer pairs for APH1B
-
OriGene qPCR primer pairs and template standards for APH1B
Gene Expression Assay Products
No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for APH1B Gene
Orthologs for APH1B Gene
This gene was present in the common ancestor of animals.
| Organism | Taxonomy | Gene | Similarity | Type | Details |
|---|---|---|---|---|---|
| Chimpanzee (Pan troglodytes) |
Mammalia | APH1B 30 31 |
|
OneToOne | |
| Mouse (Mus musculus) |
Mammalia | Aph1b 30 17 31 |
|
OneToMany | |
| Aph1c 31 |
|
OneToMany | |||
| Dog (Canis familiaris) |
Mammalia | APH1B 30 31 |
|
OneToOne | |
| Cow (Bos Taurus) |
Mammalia | APH1B 31 |
|
OneToOne | |
| Platypus (Ornithorhynchus anatinus) |
Mammalia | APH1B 31 |
|
OneToOne | |
| Chicken (Gallus gallus) |
Aves | -- 31 |
|
ManyToMany | |
| Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
ManyToMany | |
| Zebrafish (Danio rerio) |
Actinopterygii | aph1b 31 |
|
OneToOne | |
| Fruit Fly (Drosophila melanogaster) |
Insecta | aph-1 31 |
|
OneToMany | |
| Worm (Caenorhabditis elegans) |
Secernentea | aph-1 31 |
|
OneToMany | |
| Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.7022 31 |
|
OneToMany |
- Species where no ortholog for APH1B was found in the sources mined by GeneCards:
-
- A. gosspyii yeast (Eremothecium gossypii)
- Actinobacteria (Mycobacterium tuberculosis)
- African clawed frog (Xenopus laevis)
- 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)
- Oppossum (Monodelphis domestica)
- Orangutan (Pongo pygmaeus)
- Pig (Sus scrofa)
- Rainbow Trout (Oncorhynchus mykiss)
- Rat (Rattus norvegicus)
- Rice (Oryza sativa)
- Rice Blast Fungus (Magnaporthe grisea)
- Schistosome Parasite (Schistosoma mansoni)
- Sea Anemone (Nematostella vectensis)
- Sea Vase (Ciona intestinalis)
- 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)
- Tropical Clawed Frog (Silurana tropicalis)
- Wheat (Triticum aestivum)
Evolution for APH1B Gene
- ENSEMBL:
- Gene Tree for APH1B (if available)
- TreeFam:
- Gene Tree for APH1B (if available)
- Aminode:
- Evolutionary constrained regions (ECRs) for APH1B: view image
Paralogs for APH1B Gene
Variants for APH1B Gene
Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for APH1B Gene
| SNP ID | Clinical significance and condition | Chr 15 pos | Variation | AA Info | Type |
|---|---|---|---|---|---|
| rs1047552 | - | p.Phe217Leu |
| Variant ID | Type | Subtype | PubMed ID |
|---|---|---|---|
| nsv1035441 | CNV | gain | 25217958 |
| nsv428305 | CNV | gain | 18775914 |
Residual Variation Intolerance Score:
77.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score:
5.09;
69.03% of all genes are more intolerant (likely to be disease-causing)
Additional Variant Information for APH1B Gene
SNP Genotyping and Copy Number Assay Products
No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for APH1B Gene
Disorders for APH1B Gene
| Disorder | Aliases | PubMed IDs |
|---|---|---|
| alzheimer disease |
|
|
| aortic valve disease 1 |
|
|
Search APH1B in MalaCards
View complete list of genes associated with diseases
Additional Disease Information for APH1B
- Genetic Association Database
- (GAD)
- Human Genome Epidemiology Navigator
- (HuGE)
- ATLAS of Genetics and Cytogenetics in Oncology and Haematology
- Open Targets Platform
No data available for UniProtKB/Swiss-Prot and Genatlas for APH1B Gene
Publications for APH1B Gene
- Interaction between the APOE epsilon4 allele and the APH-1b c + 651T > G SNP in Alzheimer's disease. (PMID: 17466415) Poli M … Finazzi D (Neurobiology of aging 2008) 3 23 41
- Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. (PMID: 11230166) Wiemann S … Poustka A (Genome research 2001) 2 3 4
- Correlation between HIV-1 seropositivity and prevalence of a gamma-secretase polymorphism in two distinct ethnic populations. (PMID: 19774691) van Loo KM … Martens GJ (Journal of medical virology 2009) 3 41
- Male-specific association between a gamma-secretase polymorphism and premature coronary atherosclerosis. (PMID: 18987747) van Loo KM … Martens GJ (PloS one 2008) 3 41
- Characterization of APH-1 mutants with a disrupted transmembrane GxxxG motif. (PMID: 16757808) Araki W … Murayama KS (Journal of molecular neuroscience : MN 2006) 3 23
ExternalLinks
Products for APH1B Gene
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- antibodies-online: Show 23 available Aph 1b Antibodies ranked by validation data
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- antibodies-online: Show 3 available Aph 1b Proteins ranked by validation data
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Sources for APH1B Gene
- (1) GeneCards
- (2) HGNC
- (3) NCBI Entrez Gene
- (4) UniProtKB/Swiss-Prot
- (5) Ensembl
- (6) OMIM
- (7) GeneLoc
- (8) Gene Wiki
- (9) UCSC
- (10) PhosphoSitePlus
- (11) Cell Signaling Technology
- (12) GO
- (13) UniProtKB/TrEMBL
- (14) InterPro
- (15) ProtoNet
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