Seroatlas · Human Serome Atlas

GSAP

Gamma-secretase-activating protein

Also known as: GSAP_HUMAN, LOC54103, PION

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
A4D1B5
Gene
GSAP
Ensembl
ENSG00000186088
Chromosome
7
Canonical length
854 aa
Protein class
Predicted intracellular proteins
Subcellular location
Vesicles

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

854 residues, UniProt reviewed canonical sequence.

>A4D1B5|GSAP
     1  MALRLVADFD LGKDVLPWLR AQRAVSEASG AGSGGADVLE NDYESLHVLN VERNGNIIYT
    61  YKDDKGNVVF GLYDCQTRQN ELLYTFEKDL QVFSCSVNSE RTLLAASLVQ STKEGKRNEL
   121  QPGSKCLTLL VEIHPVNNVK VLKAVDSYIW VQFLYPHIES HPLPENHLLL ISEEKYIEQF
   181  RIHVAQEDGN RVVIKNSGHL PRDRIAEDFV WAQWDMSEQR LYYIDLKKSR SILKCIQFYA
   241  DESYNLMFEV PLDISLSNSG FKLVNFGCDY HQYRDKFSKH LTLCVFTNHT GSLCVCYSPK
   301  CASWGQITYS VFYIHKGHSK TFTTSLENVG SHMTKGITFL NLDYYVAVYL PGHFFHLLNV
   361  QHPDLICHNL FLTGNNEMID MLPHCPLQSL SGSLVLDCCS GKLYRALLSQ SSLLQLLQNT
   421  CLDCEKMAAL HCALYCGQGA QFLEAQIIQW ISENVSACHS FDLIQEFIIA SSYWSVYSET
   481  SNMDKLLPHS SVLTWNTEIP GITLVTEDIA LPLMKVLSFK GYWEKLNSNL EYVKYAKPHF
   541  HYNNSVVRRE WHNLISEEKT GKRRSAAYVR NILDNAVKVI SNLEARNLGP RLTPLLQEED
   601  SHQRLLMGLM VSELKDHFLR HLQGVEKKKI EQMVLDYISK LLDLICHIVE TNWRKHNLHS
   661  WVLHFNSRGS AAEFAVFHIM TRILEATNSL FLPLPPGFHT LHTILGVQCL PLHNLLHCID
   721  SGVLLLTETA VIRLMKDLDN TEKNEKLKFS IIVRLPPLIG QKICRLWDHP MSSNIISRNH
   781  VTRLLQNYKK QPRNSMINKS SFSVEFLPLN YFIEILTDIE SSNQALYPFE GHDNVDAEFV
   841  EEAALKHTAM LLGL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GSAP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.26
Highest tissue expression
18 nTPM

Expression across tissuesHPA

Tissue

  • spleen: 18 nTPM
  • lung: 17 nTPM
  • liver: 15 nTPM
  • tonsil: 12 nTPM
  • lymph node: 12 nTPM
  • parathyroid gland: 11 nTPM

Single-cell type

  • nk-cells: 285 nCPM
  • b-cells: 248 nCPM
  • kupffer cells: 203 nCPM
  • macrophages: 196 nCPM
  • microglia: 194 nCPM
  • neutrophils: 174 nCPM

Immune cell

  • myeloid DC: 16 nTPM
  • memory B-cell: 16 nTPM
  • NK-cell: 15 nTPM
  • naive B-cell: 14 nTPM
  • classical monocyte: 13 nTPM
  • intermediate monocyte: 12 nTPM

Brain region

  • hypothalamus: 6.9 nTPM
  • white matter: 6.5 nTPM
  • choroid plexus: 5.9 nTPM
  • thalamus: 5.8 nTPM
  • medulla oblongata: 5.7 nTPM
  • midbrain: 5.3 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
1
gnomAD pLI
0
gnomAD missense Z
0.53
DepMap mean gene effect
0.04
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

  • Gamma-secretase-activating protein family
  • Gamma-secretase-activating protein, C-terminal domain
  • gamma-Secretase-activating protein C-term

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of GSAP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads GSAP as an antibody target. Whether an autoantibody or antibody against GSAP could matter depends on whether native GSAP is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

GSAP is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label GSAP as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/GSAP. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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