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

    Gene ID: 54103, updated on 2-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
    mouse all
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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 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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    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)

    Genotypes

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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