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GSAP gamma-secretase activating protein [ Homo sapiens (human) ]

Gene ID: 54103, updated on 27-Nov-2024

Summary

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Official Symbol
GSAPprovided by HGNC
Official Full Name
gamma-secretase activating proteinprovided by HGNC
Primary source
HGNC:HGNC:28042
See related
Ensembl:ENSG00000186088 MIM:613552; AllianceGenome:HGNC:28042
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PION
Summary
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]
Expression
Ubiquitous expression in lung (RPKM 10.9), spleen (RPKM 10.4) and 25 other tissues See more
Orthologs
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Genomic context

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See GSAP in Genome Data Viewer
Location:
7q11.23
Exon count:
37
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (77310751..77416630, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (78561812..78667706, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (76940068..77045666, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene coiled-coil domain containing 146 Neighboring gene uncharacterized LOC105375359 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18319 Neighboring gene uncharacterized LOC102723791 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:76900911-76901093 Neighboring gene NANOG hESC enhancer GRCh37_chr7:76945409-76945910 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr7:76977350-76977924 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:77021860-77023059 Neighboring gene uncharacterized LOC101927243 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18320 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18321 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18322 Neighboring gene small nucleolar RNA U13 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:77054393-77055091 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:77055092-77055789 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr7:77056489-77057185 Neighboring gene glucosaminyl (N-acetyl) transferase 1 pseudogene 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Frontal Cortex and Hippocampal γ-Secretase Activating Protein Levels in Prodromal Alzheimer Disease. Perez SE, et al. Neurodegener Dis, 2017. PMID 28743126, Free PMC Article
  2. Common GSAP promoter variant contributes to Alzheimer's disease liability. Zhu M, et al. Neurobiol Aging, 2014 Nov. PMID 25037285
  3. Purification and characterization of the human γ-secretase activating protein. Deatherage CL, et al. Biochemistry, 2012 Jun 26. PMID 22681044, Free PMC Article
  4. Immunohistochemical characterization of γ-secretase activating protein expression in Alzheimer's disease brains. Satoh J, et al. Neuropathol Appl Neurobiol, 2012 Apr. PMID 21718343
  5. GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease. Xu P, et al. J Exp Med, 2021 Aug 2. PMID 34156424, Free PMC Article

See all (15) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease.
    Title: GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease.
  2. These data demonstrate that GSAP proteins are differentially dysregulated in severe Alzheimer Disease, but only the full-length form was associated with cognitive test scores in Alzheimer Disease.
    Title: Frontal Cortex and Hippocampal γ-Secretase Activating Protein Levels in Prodromal Alzheimer Disease.
  3. GSAP cleavage via caspase-3 is regulated and depend upon the availability of 5-Lipoxygenase in Alzheimer's disease.
    Title: Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence.
  4. Its promoter variant contributes to Alzheimer's disease liability.
    Title: Common GSAP promoter variant contributes to Alzheimer's disease liability.
  5. gamma-secretase activating protein (GSAP) and imatinib have roles in the regulation of gamma-secretase activity and amyloid-beta generation
    Title: The role of γ-secretase activating protein (GSAP) and imatinib in the regulation of γ-secretase activity and amyloid-β generation.
  6. Protocols for recombinant bacterial expression and purification of potentially important protein GSAP are not successful in generating soluble forms of GSAP that contain well-ordered and homogeneous tertiary structure.
    Title: Purification and characterization of the human γ-secretase activating protein.
  7. Aberrant regulation of gamma-secretase activating protein expression plays a key role in acceleration of gamma-cleavage of beta-secretase-cleaved C-terminal fragment of amyloid precursor protein and accumulation of Abeta in AD brains
    Title: Immunohistochemical characterization of γ-secretase activating protein expression in Alzheimer's disease brains.
  8. A gamma-secretase activating protein (GSAP) that selectively increases amyloid-beta production via interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment.
    Title: Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease.
Submit: New GeneRIF Correction

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC126548, DKFZp667B242

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables amyloid-beta binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in positive regulation of amyloid-beta formation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of amyloid-beta formation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in trans-Golgi network IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in trans-Golgi network IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
gamma-secretase-activating protein
Names
pigeon homolog
protein pigeon homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001350896.2 → NP_001337825.1  gamma-secretase-activating protein isoform b

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635
    Conserved Domains (1) summary
    pfam14959
    Location:642 → 749
    GSAP-16; gamma-Secretase-activating protein C-term

  2. NM_001350897.2 → NP_001337826.1  gamma-secretase-activating protein isoform c

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635
    Conserved Domains (1) summary
    pfam14959
    Location:624 → 731
    GSAP-16; gamma-Secretase-activating protein C-term

  3. NM_001350898.2 → NP_001337827.1  gamma-secretase-activating protein isoform d

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635
    Conserved Domains (1) summary
    pfam14959
    Location:623 → 730
    GSAP-16; gamma-Secretase-activating protein C-term

  4. NM_001350899.2 → NP_001337828.1  gamma-secretase-activating protein isoform e

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635
    Conserved Domains (1) summary
    pfam14959
    Location:642 → 749
    GSAP-16; gamma-Secretase-activating protein C-term

  5. NM_001350900.2 → NP_001337829.1  gamma-secretase-activating protein isoform f

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635
    Conserved Domains (1) summary
    pfam14959
    Location:427 → 534
    GSAP-16; gamma-Secretase-activating protein C-term

  6. NM_001350901.2 → NP_001337830.1  gamma-secretase-activating protein isoform g

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635
    Conserved Domains (1) summary
    pfam14959
    Location:395 → 502
    GSAP-16; gamma-Secretase-activating protein C-term

  7. NM_017439.4 → NP_059135.2  gamma-secretase-activating protein isoform a

    See identical proteins and their annotated locations for NP_059135.2

    Status: VALIDATED

    Source sequence(s)
    BC110797, BM842423, DB498013
    Consensus CDS
    CCDS34672.2
    UniProtKB/Swiss-Prot
    A4D1B5, A4D1B6, Q3MJC0, Q8ND73, Q9UMH3, Q9Y4L9
    Related
    ENSP00000257626.7, ENST00000257626.12
    Conserved Domains (1) summary
    pfam14959
    Location:642 → 749
    GSAP-16; gamma-Secretase-activating protein C-term

RNA

  1. NR_146937.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635

  2. NR_146938.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC004921, AC073635

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    77310751..77416630 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047420491.1 → XP_047276447.1  gamma-secretase-activating protein isoform X6

  2. XM_047420494.1 → XP_047276450.1  gamma-secretase-activating protein isoform X8

  3. XM_047420493.1 → XP_047276449.1  gamma-secretase-activating protein isoform X7

  4. XM_047420490.1 → XP_047276446.1  gamma-secretase-activating protein isoform X6

  5. XM_017012346.2 → XP_016867835.1  gamma-secretase-activating protein isoform X6

    Conserved Domains (1) summary
    pfam14959
    Location:445 → 552
    GSAP-16; gamma-Secretase-activating protein C-term

  6. XM_047420487.1 → XP_047276443.1  gamma-secretase-activating protein isoform X3

  7. XM_011516327.3 → XP_011514629.1  gamma-secretase-activating protein isoform X2

    Conserved Domains (1) summary
    pfam14959
    Location:660 → 767
    GSAP-16; gamma-Secretase-activating protein C-term

  8. XM_011516325.3 → XP_011514627.1  gamma-secretase-activating protein isoform X1

    Conserved Domains (1) summary
    pfam14959
    Location:660 → 767
    GSAP-16; gamma-Secretase-activating protein C-term

  9. XM_047420492.1 → XP_047276448.1  gamma-secretase-activating protein isoform X6

  10. XM_011516330.3 → XP_011514632.1  gamma-secretase-activating protein isoform X6

    Conserved Domains (1) summary
    pfam14959
    Location:445 → 552
    GSAP-16; gamma-Secretase-activating protein C-term

  11. XM_047420489.1 → XP_047276445.1  gamma-secretase-activating protein isoform X5

  12. XM_047420488.1 → XP_047276444.1  gamma-secretase-activating protein isoform X4

  13. XM_047420495.1 → XP_047276451.1  gamma-secretase-activating protein isoform X11

  14. XM_017012351.3 → XP_016867840.1  gamma-secretase-activating protein isoform X12

  15. XM_017012350.3 → XP_016867839.1  gamma-secretase-activating protein isoform X10

  16. XM_011516332.4 → XP_011514634.1  gamma-secretase-activating protein isoform X9

    See identical proteins and their annotated locations for XP_011514634.1

  17. XM_011516331.4 → XP_011514633.1  gamma-secretase-activating protein isoform X9

    See identical proteins and their annotated locations for XP_011514633.1

RNA

  1. XR_007060056.1 RNA Sequence

  2. XR_927479.4 RNA Sequence

  3. XR_001744817.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    78561812..78667706 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054358449.1 → XP_054214424.1  gamma-secretase-activating protein isoform X6

  2. XM_054358453.1 → XP_054214428.1  gamma-secretase-activating protein isoform X8

  3. XM_054358452.1 → XP_054214427.1  gamma-secretase-activating protein isoform X7

  4. XM_054358448.1 → XP_054214423.1  gamma-secretase-activating protein isoform X6

  5. XM_054358447.1 → XP_054214422.1  gamma-secretase-activating protein isoform X6

  6. XM_054358444.1 → XP_054214419.1  gamma-secretase-activating protein isoform X3

  7. XM_054358443.1 → XP_054214418.1  gamma-secretase-activating protein isoform X2

  8. XM_054358442.1 → XP_054214417.1  gamma-secretase-activating protein isoform X1

  9. XM_054358450.1 → XP_054214425.1  gamma-secretase-activating protein isoform X6

  10. XM_054358451.1 → XP_054214426.1  gamma-secretase-activating protein isoform X6

  11. XM_054358446.1 → XP_054214421.1  gamma-secretase-activating protein isoform X5

  12. XM_054358445.1 → XP_054214420.1  gamma-secretase-activating protein isoform X4

  13. XM_054358457.1 → XP_054214432.1  gamma-secretase-activating protein isoform X11

  14. XM_054358458.1 → XP_054214433.1  gamma-secretase-activating protein isoform X12

  15. XM_054358456.1 → XP_054214431.1  gamma-secretase-activating protein isoform X10

  16. XM_054358455.1 → XP_054214430.1  gamma-secretase-activating protein isoform X9

  17. XM_054358454.1 → XP_054214429.1  gamma-secretase-activating protein isoform X9

RNA

  1. XR_008487643.1 RNA Sequence

  2. XR_008487642.1 RNA Sequence

  3. XR_008487644.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
A4D1B5.2 GenPept UniProtKB/Swiss-Prot:A4D1B5

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