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Aliases for APH1A Gene

Aliases for APH1A Gene

  • Aph-1 Homolog A, Gamma Secretase Subunit 2 3 5
  • Presenilin-Stabilization Factor 3 4
  • APH1A Gamma Secretase Subunit 2 3
  • Aph-1alpha 3 4
  • APH-1A 3 4
  • Anterior Pharynx Defective 1 Homolog A (C. Elegans) 2
  • Anterior Pharynx Defective 1 Homolog A 3
  • 6530402N02Rik 3
  • CGI-78 3
  • APH-1 3
  • PSF 4

External Ids for APH1A Gene

Previous GeneCards Identifiers for APH1A Gene

  • GC01M147051
  • GC01M148504
  • GC01M150237
  • GC01M121616

Summaries for APH1A Gene

Entrez Gene Summary for APH1A Gene

  • This gene encodes a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1 homolog B (APH1B), along with the presenilin, nicastrin, and presenilin enhancer-2 proteins. The precise function of this seven-transmembrane-domain protein is unknown though it is suspected of facilitating the association of nicastrin and presenilin in the gamma secretase complex as well as interacting with substrates of the gamma secretase complex prior to their proteolytic processing. Polymorphisms in a promoter region of this gene have been associated with an increased risk for developing sporadic Alzheimer's disease. Alternative splicing results in multiple protein-coding and non-protein-coding transcript variants. [provided by RefSeq, Aug 2011]

GeneCards Summary for APH1A Gene

APH1A (Aph-1 Homolog A, Gamma Secretase Subunit) is a Protein Coding gene. Diseases associated with APH1A include alzheimer disease. Among its related pathways are Alzheimer's disease and Notch signaling pathway (KEGG). GO annotations related to this gene include endopeptidase activity. An important paralog of this gene is APH1B.

UniProtKB/Swiss-Prot for APH1A Gene

  • Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for APH1A Gene

Genomics for APH1A Gene

Regulatory Elements for APH1A Gene

Enhancers for APH1A Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around APH1A on UCSC Golden Path with GeneCards custom track

Promoters for APH1A Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around APH1A on UCSC Golden Path with GeneCards custom track

Genomic Location for APH1A Gene

Chromosome:
1
Start:
150,265,399 bp from pter
End:
150,269,580 bp from pter
Size:
4,182 bases
Orientation:
Minus strand

Genomic View for APH1A Gene

Genes around APH1A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
APH1A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for APH1A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for APH1A Gene

Proteins for APH1A Gene

  • Protein details for APH1A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96BI3-APH1A_HUMAN
    Recommended name:
    Gamma-secretase subunit APH-1A
    Protein Accession:
    Q96BI3
    Secondary Accessions:
    • B4DQK0
    • Q5TB22
    • Q5TB23
    • Q969R6
    • Q9BVG0
    • Q9Y386

    Protein attributes for APH1A Gene

    Size:
    265 amino acids
    Molecular mass:
    28996 Da
    Quaternary structure:
    • 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.
    SequenceCaution:
    • Sequence=AAD34072.1; Type=Frameshift; Positions=243; Evidence={ECO:0000305}; Sequence=AAN63816.1; Type=Frameshift; Positions=243; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for APH1A Gene

    Alternative splice isoforms for APH1A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for APH1A Gene

Proteomics data for APH1A Gene at MOPED

Post-translational modifications for APH1A Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for APH1A Gene

Antibody Products

No data available for DME Specific Peptides for APH1A Gene

Domains & Families for APH1A Gene

Protein Domains for APH1A Gene

InterPro:
Blocks:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

Q96BI3

UniProtKB/Swiss-Prot:

APH1A_HUMAN :
  • Belongs to the APH-1 family.
Family:
  • Belongs to the APH-1 family.
genes like me logo Genes that share domains with APH1A: view

No data available for Gene Families for APH1A Gene

Function for APH1A Gene

Molecular function for APH1A Gene

UniProtKB/Swiss-Prot Function:
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.
genes like me logo Genes that share phenotypes with APH1A: view

Animal Models for APH1A Gene

MGI Knock Outs for APH1A:

Animal Model Products

  • Taconic Biosciences Mouse Models for APH1A

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for APH1A Gene

Localization for APH1A Gene

Subcellular locations from UniProtKB/Swiss-Prot for APH1A Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus, Golgi stack membrane; Multi-pass membrane protein. Note=Predominantly located in the endoplasmic reticulum and in the cis-Golgi.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for APH1A Gene COMPARTMENTS Subcellular localization image for APH1A gene
Compartment Confidence
plasma membrane 4

Gene Ontology (GO) - Cellular Components for APH1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016021 integral component of membrane IEA --
GO:0032580 Golgi cisterna membrane IEA --
genes like me logo Genes that share ontologies with APH1A: view

Pathways & Interactions for APH1A Gene

genes like me logo Genes that share pathways with APH1A: view

SIGNOR curated interactions for APH1A Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for APH1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001656 metanephros development IEA --
GO:0006509 membrane protein ectodomain proteolysis IDA 15274632
GO:0007220 Notch receptor processing TAS 15274632
GO:0007411 axon guidance TAS --
GO:0031293 membrane protein intracellular domain proteolysis TAS --
genes like me logo Genes that share ontologies with APH1A: view

Drugs & Compounds for APH1A Gene

(13) Drugs for APH1A Gene - From: DrugBank, ApexBio, and DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
E2012 Investigational Pharma Target 0
BMS-708163 (Avagacestat) Pharma γ-secretase inhibitor 0
LY2811376 Pharma Non-peptidic BACE1 inhibitor 0
LY-411575 Pharma Gamma secretase inhibitor 0
MK-0752 Pharma γ-secretase inhibitor 0

(6) ApexBio Compounds for APH1A Gene

Compound Action Cas Number
BMS-708163 (Avagacestat) γ-secretase inhibitor 1146699-66-2
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
YO-01027 (Dibenzazepine, DBZ) γ-secretase inhibitor 209984-56-5
genes like me logo Genes that share compounds with APH1A: view

Transcripts for APH1A Gene

Unigene Clusters for APH1A Gene

Anterior pharynx defective 1 homolog A (C. elegans):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for APH1A Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5a · 5b · 5c · 5d ^ 6a · 6b · 6c ^ 7
SP1: - - - - -
SP2: - - -
SP3: - -
SP4: - - - - -
SP5: -
SP6: -

Relevant External Links for APH1A Gene

GeneLoc Exon Structure for
APH1A
ECgene alternative splicing isoforms for
APH1A

Expression for APH1A Gene

mRNA expression in normal human tissues for APH1A Gene

Protein differential expression in normal tissues from HIPED for APH1A Gene

This gene is overexpressed in Adrenal (64.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MOPED, and MaxQB for APH1A Gene



SOURCE GeneReport for Unigene cluster for APH1A Gene Hs.108408

mRNA Expression by UniProt/SwissProt for APH1A Gene

Q96BI3-APH1A_HUMAN
Tissue specificity: Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain. Isoform 1 and isoform 2 are nearly expressed at the same level.
genes like me logo Genes that share expression patterns with APH1A: view

Protein tissue co-expression partners for APH1A Gene

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for APH1A Gene

Orthologs for APH1A Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for APH1A Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia APH1A 35
  • 95.93 (n)
  • 98.37 (a)
APH1A 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia APH1 35
  • 96.73 (n)
  • 99.25 (a)
APH1A 36
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Aph1a 35
  • 94.72 (n)
  • 99.25 (a)
Aph1a 16
Aph1a 36
  • 99 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia APH1A 35
  • 99.75 (n)
  • 100 (a)
APH1A 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Aph1a 35
  • 93.36 (n)
  • 98.78 (a)
oppossum
(Monodelphis domestica)
Mammalia APH1A 36
  • 89 (a)
OneToOne
chicken
(Gallus gallus)
Aves LOC431243 35
  • 72.96 (n)
  • 78.11 (a)
APH1A 36
  • 78 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia APH1A 36
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia aph1a 35
  • 67.61 (n)
  • 72.87 (a)
Str.2748 35
zebrafish
(Danio rerio)
Actinopterygii aph1b 35
  • 65.19 (n)
  • 63.86 (a)
APH1A 36
  • 62 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2866 35
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009816 35
  • 52.18 (n)
  • 47.26 (a)
fruit fly
(Drosophila melanogaster)
Insecta aph-1 35
  • 54.69 (n)
  • 49.35 (a)
aph-1 36
  • 48 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea aph-1 35
  • 43.55 (n)
  • 37.19 (a)
aph-1 36
  • 24 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G31440 35
  • 46.53 (n)
  • 29.21 (a)
rice
(Oryza sativa)
Liliopsida Os02g0272600 35
  • 48.35 (n)
  • 32.67 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.7022 36
  • 43 (a)
OneToMany
Species with no ortholog for APH1A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • platypus (Ornithorhynchus anatinus)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for APH1A Gene

ENSEMBL:
Gene Tree for APH1A (if available)
TreeFam:
Gene Tree for APH1A (if available)

Paralogs for APH1A Gene

Paralogs for APH1A Gene

(1) SIMAP similar genes for APH1A Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with APH1A: view

Variants for APH1A Gene

Sequence variations from dbSNP and Humsavar for APH1A Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs9658936 -- 150,266,588(+) GCCCA(A/G)AGCCC nc-transcript-variant, reference, synonymous-codon
rs9658939 -- 150,266,615(+) GCATA(A/G)ATGGG nc-transcript-variant, reference, synonymous-codon
rs11548265 -- 150,266,450(-) AGCCC(G/T)GGTCC intron-variant, nc-transcript-variant, utr-variant-3-prime
rs11548267 -- 150,266,299(-) TCTGC(A/G)CTTAT intron-variant, nc-transcript-variant, utr-variant-3-prime
rs17849449 -- 150,266,560(+) TCGGA(G/T)GGACC nc-transcript-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for APH1A Gene

Variant ID Type Subtype PubMed ID
nsv872415 CNV Loss 21882294

Variation tolerance for APH1A Gene

Residual Variation Intolerance Score: 48.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.54; 64.87% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for APH1A Gene

HapMap Linkage Disequilibrium report
APH1A
Human Gene Mutation Database (HGMD)
APH1A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for APH1A Gene

Disorders for APH1A Gene

MalaCards: The human disease database

(1) MalaCards diseases for APH1A Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
alzheimer disease
  • alzheimer disease, late-onset
- elite association - COSMIC cancer census association via MalaCards
Search APH1A in MalaCards View complete list of genes associated with diseases

Relevant External Links for APH1A

Genetic Association Database (GAD)
APH1A
Human Genome Epidemiology (HuGE) Navigator
APH1A
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
APH1A
genes like me logo Genes that share disorders with APH1A: view

No data available for UniProtKB/Swiss-Prot and Genatlas for APH1A Gene

Publications for APH1A Gene

  1. aph-1 and pen-2 are required for Notch pathway signaling, gamma- secretase cleavage of betaAPP, and presenilin protein accumulation. (PMID: 12110170) Francis R. … Curtis D. (Dev. Cell 2002) 2 3 4 67
  2. Chemical cross-linking provides a model of the gamma-secretase complex subunit architecture and evidence for close proximity of the C-terminal fragment of presenilin with APH-1. (PMID: 18801744) Steiner H. … Haass C. (J. Biol. Chem. 2008) 3 23
  3. Identification of distinct gamma-secretase complexes with different APH-1 variants. (PMID: 15286082) Shirotani K. … Steiner H. (J. Biol. Chem. 2004) 3 23
  4. APH1, PEN2, and nicastrin increase Abeta levels and gamma-secretase activity. (PMID: 12763021) Marlow L. … Sambamurti K. (Biochem. Biophys. Res. Commun. 2003) 3 23
  5. Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. (PMID: 10810093) Lai C.-H. … Lin W.-C. (Genome Res. 2000) 2 3

Products for APH1A Gene

Sources for APH1A Gene

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