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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
  • Anterior Pharynx Defective 1 Homolog A (C. Elegans) 2
  • Anterior Pharynx Defective 1 Homolog A 3
  • Gamma-Secretase Subunit APH-1A 3
  • 6530402N02Rik 3
  • APH-1A 3
  • CGI-78 3
  • APH-1a 4
  • 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 Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases and NOTCH2 Activation and Transmission of Signal to the Nucleus. Gene Ontology (GO) annotations related to this gene include endopeptidase activity. An important paralog of this gene is APH1B.

UniProtKB/Swiss-Prot for APH1A Gene

  • Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12297508, PubMed:12522139, PubMed:12763021, PubMed:12679784, PubMed:25043039, PubMed:26280335). Required for normal gamma-secretase assembly (PubMed:12522139, PubMed:12471034, PubMed:12763021, PubMed:19369254). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable).

Additional gene information for APH1A Gene

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

Genomics for APH1A Gene

GeneHancer (GH) Regulatory Elements for APH1A Gene

Promoters and enhancers for APH1A 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
GH01J150266 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 650.7 +1.1 1065 3.3 CLOCK ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B IRF4 YY1 POLR2B APH1A C1orf54 ARNT PIP5K1A PRUNE1 SETDB1 MRPS21 C1orf56 SEMA6C
GH01J150280 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 650.4 -12.5 -12485 3.3 HDGF PKNOX1 CLOCK SIN3A FEZF1 ZBTB7B YY1 GLIS2 ELK1 ZNF207 CIART APH1A SETDB1 ARNT PIP5K1A PRPF3 UBE2D3P3 PRUNE1 GABPB2 SF3B4
GH01J150271 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE 650.7 -3.3 -3255 2.3 PKNOX1 RB1 MZF1 SIN3A BATF IRF4 ZNF335 GLIS2 ZNF366 SCRT2 C1orf54 APH1A SEMA6C MRPS21 CIART
GH01J151068 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 27.6 -800.9 -800906 3.3 CLOCK FEZF1 IRF4 YY1 ZNF213 E2F8 ZNF416 ZNF143 ZNF548 SP3 GABPB2 CDC42SE1 SETDB1 PRPF3 PI4KB PIP5K1A MRPL9 UBE2D3P3 ARNT ZNF687
GH01J150557 Promoter/Enhancer 2.6 EPDnew Ensembl ENCODE dbSUPER 18.7 -299.7 -299724 23.1 CLOCK MLX DMAP1 IRF4 YY1 SLC30A9 E2F8 ZNF143 SP3 NFYC RN7SL600P MCL1 SETDB1 PIP5K1A PI4KB PRPF3 ARNT GOLPH3L HORMAD1 SF3B4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around APH1A on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the APH1A gene promoter:

Genomic Locations for APH1A Gene

Genomic Locations for APH1A Gene
chr1:150,265,399-150,269,580
(GRCh38/hg38)
Size:
4,182 bases
Orientation:
Minus strand
chr1:150,237,799-150,241,980
(GRCh37/hg19)

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:
    • The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2 (PubMed:12297508, PubMed:12740439, PubMed:19369254, PubMed:25043039, PubMed:26623517, PubMed:26280335).
    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

Post-translational modifications for APH1A Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for APH1A Gene

Domains & Families for APH1A Gene

Gene Families for APH1A Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for APH1A Gene

Blocks:
InterPro:
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

Function for APH1A Gene

Molecular function for APH1A Gene

UniProtKB/Swiss-Prot Function:
Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12297508, PubMed:12522139, PubMed:12763021, PubMed:12679784, PubMed:25043039, PubMed:26280335). Required for normal gamma-secretase assembly (PubMed:12522139, PubMed:12471034, PubMed:12763021, PubMed:19369254). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable).

Phenotypes From GWAS Catalog for APH1A Gene

Gene Ontology (GO) - Molecular Function for APH1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IBA --
GO:0005515 protein binding IPI 12297508
genes like me logo Genes that share ontologies with APH1A: view
genes like me logo Genes that share phenotypes with APH1A: view

Animal Models for APH1A Gene

MGI Knock Outs for APH1A:

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , 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. {ECO:0000269 PubMed:12522139}.

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 APH1A gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 5
golgi apparatus 5
lysosome 1
endosome 1

Gene Ontology (GO) - Cellular Components for APH1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IDA 15274632
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005794 Golgi apparatus IDA 15274632
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 15274632
genes like me logo Genes that share ontologies with APH1A: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for APH1A Gene

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:0007219 Notch signaling pathway TAS,IBA --
GO:0007220 Notch receptor processing TAS,IMP 15274632
GO:0016485 protein processing IDA 15274632
genes like me logo Genes that share ontologies with APH1A: view

Drugs & Compounds for APH1A Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
E-2012 Investigational Pharma Target 0
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

(11) ApexBio Compounds for APH1A 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
LY-411575 isomer 1 209984-58-7
LY-411575 isomer 2
LY-411575 isomer 3
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 APH1A: view

Drug Products

Transcripts for APH1A Gene

Unigene Clusters for APH1A Gene

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

Clone Products

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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, MaxQB, and MOPED for APH1A Gene



Protein tissue co-expression partners for APH1A Gene

NURSA nuclear receptor signaling pathways regulating expression of APH1A Gene:

APH1A

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.

Evidence on tissue expression from TISSUES for APH1A Gene

  • Nervous system(4.9)
  • Lung(4.7)
  • Eye(4.4)
  • Thyroid gland(4.4)
  • Adrenal gland(4.3)
  • Intestine(3.6)
  • Skin(2.9)
  • Blood(2.7)
  • Kidney(2.4)
  • Liver(2)
genes like me logo Genes that share expression patterns with APH1A: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
chimpanzee
(Pan troglodytes)
Mammalia APH1A 34 33
  • 99.75 (n)
OneToOne
dog
(Canis familiaris)
Mammalia APH1A 34
  • 99 (a)
OneToOne
APH1 33
  • 96.73 (n)
cow
(Bos Taurus)
Mammalia APH1A 34 33
  • 95.93 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Aph1a 16 34 33
  • 94.72 (n)
rat
(Rattus norvegicus)
Mammalia Aph1a 33
  • 93.36 (n)
oppossum
(Monodelphis domestica)
Mammalia APH1A 34
  • 89 (a)
OneToOne
chicken
(Gallus gallus)
Aves APH1A 34
  • 78 (a)
OneToOne
LOC431243 33
  • 72.96 (n)
lizard
(Anolis carolinensis)
Reptilia APH1A 34
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia aph1a 33
  • 67.61 (n)
Str.2748 33
zebrafish
(Danio rerio)
Actinopterygii aph1b 33 33
  • 65.19 (n)
APH1A 34
  • 62 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2866 33
fruit fly
(Drosophila melanogaster)
Insecta aph-1 34 33
  • 54.69 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009816 33
  • 52.18 (n)
worm
(Caenorhabditis elegans)
Secernentea aph-1 34 33
  • 43.55 (n)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G31440 33
  • 46.53 (n)
rice
(Oryza sativa)
Liliopsida Os02g0272600 33
  • 48.35 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.7022 34
  • 43 (a)
OneToMany
Species where no ortholog for APH1A was found in the sources mined by GeneCards:
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for APH1A: view image

Paralogs for APH1A Gene

Paralogs for APH1A Gene

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

  • APH1A_HUMAN
  • Q5TB21_HUMAN
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 Variation AA Info Type
rs1000017680 -- 150,268,281(-) G/C intron_variant
rs1000163033 -- 150,280,513(-) G/A genic_upstream_transcript_variant, intron_variant
rs1000336066 -- 150,273,175(-) G/A genic_upstream_transcript_variant, intron_variant
rs1001581857 -- 150,279,212(-) C/T genic_upstream_transcript_variant, intron_variant
rs1002071391 -- 150,265,979(-) C/T 3_prime_UTR_variant, non_coding_transcript_variant

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

Variant ID Type Subtype PubMed ID
nsv1009508 CNV loss 25217958
nsv1011223 CNV gain 25217958

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)

Additional Variant Information for APH1A Gene

Human Gene Mutation Database (HGMD)
APH1A
SNPedia medical, phenotypic, and genealogical associations of SNPs for
APH1A

SNP Genotyping and Copy Number Assay Products

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
  • ad
- elite association - COSMIC cancer census association via MalaCards
Search APH1A in MalaCards View complete list of genes associated with diseases

Additional Disease Information for APH1A

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 APH1A: view

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

Publications for APH1A Gene

  1. APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity. (PMID: 12763021) Marlow L … Sambamurti K (Biochemical and biophysical research communications 2003) 3 4 22 58
  2. 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 (Developmental cell 2002) 2 3 4 58
  3. Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. (PMID: 10810093) Lai CH … Lin W (Genome research 2000) 2 3 4 58
  4. An atomic structure of human γ-secretase. (PMID: 26280335) Bai XC … Shi Y (Nature 2015) 3 4 58
  5. Three-dimensional structure of human γ-secretase. (PMID: 25043039) Lu P … Shi Y (Nature 2014) 3 4 58

Products for APH1A Gene

Sources for APH1A Gene

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