Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amylo... See more...

Aliases for GSAP Gene

Aliases for GSAP Gene

  • Gamma-Secretase Activating Protein 2 3 5
  • Gamma-Secretase-Activating Protein 3 4
  • Protein Pigeon Homolog 3 4
  • PION 3 4
  • Pigeon Homolog (Drosophila) 2
  • Pigeon Homolog 3

External Ids for GSAP Gene

Previous HGNC Symbols for GSAP Gene

  • PION

Previous GeneCards Identifiers for GSAP Gene

  • GC07M076941

Summaries for GSAP Gene

Entrez Gene Summary for GSAP Gene

  • Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]

GeneCards Summary for GSAP Gene

GSAP (Gamma-Secretase Activating Protein) is a Protein Coding gene. Diseases associated with GSAP include Alzheimer Disease. Gene Ontology (GO) annotations related to this gene include amyloid-beta binding.

UniProtKB/Swiss-Prot Summary for GSAP Gene

  • Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid-beta, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD.

Gene Wiki entry for GSAP Gene

Additional gene information for GSAP Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GSAP Gene

Genomics for GSAP Gene

GeneHancer (GH) Regulatory Elements for GSAP Gene

Promoters and enhancers for GSAP 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
GH07J077412 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 797.8 +1.4 1413 5.1 CTCF RBPJ POU5F1 ZNF652 NKRF POLR2A MAFK ZSCAN21 ZNF687 PRDM1 GSAP ENSG00000273341 LOC101927243 PTPN12 PMS2P9 lnc-CCDC146-3
GH07J077326 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 771.8 +88.8 88812 3.2 MYC HLF MAX MNT CEBPG CEBPA IKZF2 CEBPB EED BCL11A GSAP FGL2 PTPN12 DTX2 lnc-FGL2-6-001 lnc-FGL2-6-002 piR-53029-119 CCDC146
GH07J077425 Promoter/Enhancer 1.6 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 38.1 -11.0 -10993 4.6 IKZF1 RNF2 RXRA PRDM10 SOX13 EED RUNX3 FOS NR2F2 ZSCAN9 lnc-GSAP-6 GSAP PTPN12 RF01210-360 ENSG00000273341 LOC101927243
GH07J077408 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 43.6 +6.2 6150 4.1 SIN3A LCORL FOXA1 MLX NR2F6 CREB1 MIXL1 HLF RAD21 SREBF1 GSAP PTPN12 LOC101927243 lnc-CCDC146-3
GH07J077453 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 29.5 -44.2 -44193 16 ZNF24 CTCF FOXA1 MLX NR2F6 MIXL1 ETV6 HLF RAD21 RERE GCNT1P5 lnc-PTPN12-2 GSAP PTPN12 FGL2 piR-42491-209
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GSAP on UCSC Golden Path with GeneCards custom track

Genomic Locations for GSAP Gene

Genomic Locations for GSAP Gene
chr7:77,310,751-77,416,408
(GRCh38/hg38)
Size:
105,658 bases
Orientation:
Minus strand
chr7:76,940,068-77,045,717
(GRCh37/hg19)
Size:
105,650 bases
Orientation:
Minus strand

Genomic View for GSAP Gene

Genes around GSAP on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for GSAP Gene

Proteins for GSAP Gene

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

    Protein Symbol:
    A4D1B5-GSAP_HUMAN
    Recommended name:
    Gamma-secretase-activating protein
    Protein Accession:
    A4D1B5
    Secondary Accessions:
    • A4D1B6
    • Q3MJC0
    • Q8ND73
    • Q9UMH3
    • Q9Y4L9

    Protein attributes for GSAP Gene

    Size:
    854 amino acids
    Molecular mass:
    97802 Da
    Quaternary structure:
    • Interacts with APP; specifically interacts with the CTF-alpha product of APP. Interacts with the gamma-secretase complex.
    Miscellaneous:
    • The gamma-secretase regulator activity is specifically inhibited by imatinib (also known as STI571 or Gleevec), an anticancer drug that selectively decreases amyloid-beta protein production. Imatinib binds PION/GSAP and acts by preventing PION/GSAP interaction with the gamma-secretase substrate, CTF-alpha (PubMed:20811458).
    • Its role as an activator of amyloid-beta protein production makes it a promising therapeutic target for the treatment of Alzheimer disease.
    SequenceCaution:
    • Sequence=CAD39023.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for GSAP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GSAP Gene

Post-translational modifications for GSAP Gene

  • The protein is first synthesized as a holoprotein form of 98 kDa and rapidly processed into the gamma-secretase-activating protein 16 kDa C-terminal form, which constitutes the predominant form.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for GSAP Gene

Domains & Families for GSAP Gene

Gene Families for GSAP Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for GSAP Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GSAP Gene

GenScript: Design optimal peptide antigens:
  • Protein pigeon homolog (GSAP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

A4D1B5

UniProtKB/Swiss-Prot:

GSAP_HUMAN :
  • Belongs to the GSAP family.
Family:
  • Belongs to the GSAP family.
genes like me logo Genes that share domains with GSAP: view

Function for GSAP Gene

Molecular function for GSAP Gene

UniProtKB/Swiss-Prot Function:
Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid-beta, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD.

Phenotypes From GWAS Catalog for GSAP Gene

Gene Ontology (GO) - Molecular Function for GSAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001540 amyloid-beta binding IDA 20811458
GO:0005515 protein binding IPI 20811458
genes like me logo Genes that share ontologies with GSAP: view
genes like me logo Genes that share phenotypes with GSAP: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

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

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for GSAP Gene

Localization for GSAP Gene

Subcellular locations from UniProtKB/Swiss-Prot for GSAP Gene

Golgi apparatus, trans-Golgi network.

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 GSAP gene
Compartment Confidence
golgi apparatus 5
nucleus 2
cytosol 2
plasma membrane 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GSAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005794 Golgi apparatus IEA --
GO:0005802 trans-Golgi network IDA 20811458
genes like me logo Genes that share ontologies with GSAP: view

Pathways & Interactions for GSAP Gene

PathCards logo

SuperPathways for GSAP Gene

No Data Available

Gene Ontology (GO) - Biological Process for GSAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0030162 regulation of proteolysis IDA 20811458
GO:1902004 positive regulation of amyloid-beta formation IDA 20811458
genes like me logo Genes that share ontologies with GSAP: view

No data available for Pathways by source and SIGNOR curated interactions for GSAP Gene

Drugs & Compounds for GSAP Gene

No Compound Related Data Available

Transcripts for GSAP Gene

CRISPR Products

Inhibitory RNA Products

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

Clone Products

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

No ASD Table

Relevant External Links for GSAP Gene

GeneLoc Exon Structure for
GSAP
ECgene alternative splicing isoforms for
GSAP

Expression for GSAP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for GSAP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for GSAP Gene

This gene is overexpressed in Peripheral blood mononuclear cells (59.8) and Brain (9.2).

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



Protein tissue co-expression partners for GSAP Gene

NURSA nuclear receptor signaling pathways regulating expression of GSAP Gene:

GSAP

mRNA Expression by UniProt/SwissProt for GSAP Gene:

A4D1B5-GSAP_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for GSAP Gene

  • Nervous system(4.4)
  • Lymph node(4.2)
genes like me logo Genes that share expression patterns with GSAP: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for GSAP Gene

Orthologs for GSAP Gene

This gene was present in the common ancestor of animals.

Orthologs for GSAP Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PION 33 32
  • 99.18 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GSAP 33 32
  • 88.28 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PION 33 32
  • 87.51 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Gsap 17 33 32
  • 79.92 (n)
rat
(Rattus norvegicus)
Mammalia Gsap 32
  • 78.89 (n)
oppossum
(Monodelphis domestica)
Mammalia GSAP 33
  • 66 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 33
  • 57 (a)
OneToMany
-- 33
  • 50 (a)
OneToMany
chicken
(Gallus gallus)
Aves PION 32
  • 65.87 (n)
GSAP 33
  • 57 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GSAP 33
  • 49 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii gsap 33 32
  • 54.24 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008636 32
  • 40.04 (n)
fruit fly
(Drosophila melanogaster)
Insecta pigeon 33 32
  • 39.63 (n)
OneToOne
Species where no ortholog for GSAP 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)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for GSAP Gene

ENSEMBL:
Gene Tree for GSAP (if available)
TreeFam:
Gene Tree for GSAP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GSAP: view image

Paralogs for GSAP Gene

(2) SIMAP similar genes for GSAP Gene using alignment to 3 proteins:

  • GSAP_HUMAN
  • C9JRG7_HUMAN
  • H7C0Q7_HUMAN
genes like me logo Genes that share paralogs with GSAP: view

No data available for Paralogs for GSAP Gene

Variants for GSAP Gene

Sequence variations from dbSNP and Humsavar for GSAP Gene

SNP ID Clin Chr 07 pos Variation AA Info Type
rs56314229 benign, not specified 77,377,401(-) AAAAAAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAA/AAAAAAAAAAAAAA/AAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAAAAAAAAA/AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA intron_variant
rs1000009606 -- 77,381,366(-) AAACAAAGAAA/AAA genic_upstream_transcript_variant, intron_variant, upstream_transcript_variant
rs1000015116 -- 77,353,170(-) T/G intron_variant
rs1000037356 -- 77,414,613(-) C/A genic_upstream_transcript_variant, intron_variant
rs1000046717 -- 77,394,411(-) T/C genic_upstream_transcript_variant, intron_variant

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

Variant ID Type Subtype PubMed ID
esv3308017 CNV mobile element insertion 20981092
esv3343961 CNV insertion 20981092
esv3613797 CNV loss 21293372
nsv1022292 CNV gain 25217958
nsv1032907 CNV gain 25217958
nsv1137259 CNV deletion 24896259
nsv366800 CNV deletion 16902084
nsv951364 CNV duplication 24416366

Variation tolerance for GSAP Gene

Residual Variation Intolerance Score: 32.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.97; 87.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GSAP Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GSAP

SNP Genotyping and Copy Number Assay Products

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

Disorders for GSAP Gene

MalaCards: The human disease database

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

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

Additional Disease Information for GSAP

genes like me logo Genes that share disorders with GSAP: view

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

Publications for GSAP Gene

  1. Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. (PMID: 20811458) He G … Greengard P (Nature 2010) 2 3 4 56
  2. Human chromosome 7: DNA sequence and biology. (PMID: 12690205) Scherer SW … Tsui LC (Science (New York, N.Y.) 2003) 3 4 56
  3. Frontal Cortex and Hippocampal γ-Secretase Activating Protein Levels in Prodromal Alzheimer Disease. (PMID: 28743126) Perez SE … Mufson EJ (Neuro-degenerative diseases 2017) 3 56
  4. Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence. (PMID: 26076991) Chu J … Praticò D (Scientific reports 2015) 3 56
  5. Prolyl oligopeptidase enhances α-synuclein dimerization via direct protein-protein interaction. (PMID: 25555914) Savolainen MH … Huttunen HJ (The Journal of biological chemistry 2015) 3 56

Products for GSAP Gene

Sources for GSAP Gene