APH1B Gene (Protein Coding)

Aph-1 Homolog B, Gamma-Secretase Subunit

GC15P074045
GIFtS:
43
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

  • Aph-1 Homolog B, Gamma-Secretase Subunit 2 3 5
  • PSFL 2 3 4
  • Gamma-Secretase Subunit APH-1B 3 4
  • APH1B Gamma Secretase Subunit 2 3
  • Aph-1beta 3 4
  • APH-1B 2 3
  • Anterior Pharynx Defective 1 Homolog B (C. Elegans) 2
  • Anterior Pharynx Defective 1 Homolog B 3
  • Presenilin-Stabilization Factor-Like 4
  • DKFZp564D0372 2
  • PRO1328 3
  • TAAV688 3
  • APH-1b 4
  • APH1B 5

External Ids for APH1B Gene

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
  • GC15P072972

Summaries for APH1B Gene

Entrez Gene Summary 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 Immunodeficiency 51 and Aortic Valve Disease 1. Among its related pathways are NOTCH2 Activation and Transmission of Signal to the Nucleus and IL-2 Pathway. 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

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

Download GeneHancer 2017 data
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

Latest Assembly
chr15:63,276,018-63,309,126
(GRCh38/hg38)
Size:
33,109 bases
Orientation:
Plus strand

Previous Assembly
chr15:63,569,804-63,601,325
(GRCh37/hg19 by Entrez Gene)
Size:
31,522 bases
Orientation:
Plus strand

chr15:63,568,217-63,601,325
(GRCh37/hg19 by Ensembl)
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:
APH1B Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for APH1B Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for APH1B Gene

Proteins for APH1B Gene

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  • Protein details for APH1B Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WW43-APH1B_HUMAN
    Recommended name:
    Gamma-secretase subunit APH-1B
    Protein Accession:
    Q8WW43
    Secondary Accessions:
    • 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.

    Alternative splice isoforms for APH1B Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for APH1B Gene

Protein Expression for APH1B Gene

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

Post-translational modifications for APH1B Gene

  • Ubiquitination at Lys247
  • Modification sites at PhosphoSitePlus

Other Protein References for APH1B Gene

ENSEMBL proteins:
REFSEQ proteins:

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

Protein Domains for APH1B Gene

InterPro:
Blocks:
  • Aph-1
ProtoNet:

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

UniProtKB/Swiss-Prot:

APH1B_HUMAN :
  • Belongs to the APH-1 family.
Family:
  • Belongs to the APH-1 family.
genes like me logo Genes that share domains with APH1B: view

Function for APH1B Gene

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  6. Cell Lines for research

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

Gene Ontology (GO) - Molecular Function for APH1B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IBA --
GO:0005515 protein binding IPI 12297508
GO:0008233 peptidase activity IDA 12297508
GO:0030674 protein binding, bridging IMP 12297508
GO:0061133 endopeptidase activator activity IMP 12297508
genes like me logo Genes that share ontologies with APH1B: view
genes like me logo Genes that share phenotypes with APH1B: view

Animal Models for APH1B Gene

MGI Knock Outs for APH1B:

Animal Models for research

miRNA for APH1B Gene

miRTarBase miRNAs that target APH1B

Inhibitory RNAs for research

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

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 APH1B gene
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

Gene Ontology (GO) - Cellular Components for APH1B Gene

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 --
GO:0010008 endosome membrane TAS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with APH1B: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for APH1B Gene

Pathways & Interactions for APH1B Gene

genes like me logo Genes that share pathways with APH1B: view

Pathways by source for APH1B Gene

1 Sino Biological pathway 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

SIGNOR curated interactions for APH1B Gene

Activates:

Gene Ontology (GO) - Biological Process for APH1B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007219 Notch signaling pathway IEA,IBA 21873635
GO:0007220 Notch receptor processing IDA 27608597
GO:0007626 locomotory behavior IEA --
GO:0010950 positive regulation of endopeptidase activity IMP 12297508
GO:0016485 protein processing IEA,IGI 12763021
genes like me logo Genes that share ontologies with APH1B: view

Drugs & Compounds for APH1B Gene

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(13) Drugs for APH1B Gene - From: ApexBio and DGIdb

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
genes like me logo Genes that share compounds with APH1B: view

Drug products for research

Transcripts for APH1B Gene

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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 :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for APH1B

Alternative Splicing Database (ASD) splice patterns (SP) for APH1B Gene

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

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  1. Primer products for research
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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for APH1B Gene

mRNA expression in normal human tissues for APH1B Gene
mRNA expression by GTEx for APH1B GenemRNA expression by BioGPS for APH1B Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for APH1B Gene

This gene is overexpressed in Testis (x5.1).

Protein differential expression in normal tissues from HIPED for APH1B Gene

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



Protein tissue co-expression partners for APH1B Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for APH1B

SOURCE GeneReport for Unigene cluster for APH1B Gene:

Hs.511703

mRNA 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)
genes like me logo Genes that share expression patterns with APH1B: view

Primer products for research

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.

Orthologs for APH1B Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia APH1B 30 31
  • 99.22 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Aph1b 30 17 31
  • 86.64 (n)
 OneToMany
Aph1c 31
  • 81 (a)
 OneToMany
Dog
(Canis familiaris)
 Mammalia APH1B 30 31
  • 86.22 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia APH1B 31
  • 81 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia APH1B 31
  • 59 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves -- 31
  • 55 (a)
 ManyToMany
Lizard
(Anolis carolinensis)
 Reptilia -- 31
  • 62 (a)
 ManyToMany
Zebrafish
(Danio rerio)
 Actinopterygii aph1b 31
  • 63 (a)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta aph-1 31
  • 46 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea aph-1 31
  • 24 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea CSA.7022 31
  • 46 (a)
 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

Paralogs for APH1B Gene

(2) SIMAP similar genes for APH1B Gene using alignment to 4 proteins:

  • APH1B_HUMAN
  • H0YKZ9_HUMAN
  • H0YLT0_HUMAN
  • H0YM95_HUMAN

Pseudogenes.org Pseudogenes for APH1B Gene

genes like me logo Genes that share paralogs with APH1B: view

Variants for APH1B Gene

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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

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for APH1B 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 APH1B Gene

Variant ID Type Subtype PubMed ID
nsv1035441 CNV gain 25217958
nsv428305 CNV gain 18775914

Variation tolerance for APH1B Gene

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

Human Gene Mutation Database (HGMD)
APH1B
SNPedia medical, phenotypic, and genealogical associations of SNPs for
APH1B

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for APH1B Gene

Disorders for APH1B Gene

MalaCards: The human disease database

(2) MalaCards diseases for APH1B Gene - From: COP

Disorder Aliases PubMed IDs
immunodeficiency 51
  • imd51
aortic valve disease 1
  • aovd1
- elite association - COSMIC cancer census association via MalaCards
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
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with APH1B: view

No data available for UniProtKB/Swiss-Prot and Genatlas for APH1B Gene

Publications for APH1B Gene

  1. 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
  2. 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
  3. 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
  4. Male-specific association between a gamma-secretase polymorphism and premature coronary atherosclerosis. (PMID: 18987747) van Loo KM … Martens GJ (PloS one 2008) 3 41
  5. 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

View latest publications for APH1B gene in Mastermind

Products for APH1B Gene

  • Addgene plasmids for APH1B

Sources for APH1B Gene