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Symbol PSAP contributors: mct - updated : 05-07-2017
HGNC name prosaposin
HGNC id 9498
Corresponding disease
SAPA saposin A deficiency
SAPB saposin B deficiency
SAPC Gaucher disease, variant C
SAPD saposin D deficiency
Location 10q22.1      Physical location : 73.576.055 - 73.611.082
Synonym name
  • sphingolipid activator protein 1
  • cerebroside sulfate activator protein
  • Synonym symbol(s) SAP1, GLBA, SAPA, SAP2, SAPC, MGC110993, SGP-1
    TYPE functioning gene
    text multicystronic
    STRUCTURE 35.03 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - D10S1672 - [D10S1688 - D10S556 - D10S607 ] - D10S1786 - qter
    Text [PSAP ]
    Physical map
    OT7T022 10q21-q22 neuropeptide FF 1; RFamide-related peptide receptor FLJ10751 10q22.2 hypothetical protein FLJ10751 LOC221017 10q22.2 similar to chromosome 6 open reading frame 182 EIF4EBP2 10q21-q22 eukaryotic translation initiation factor 4E binding protein 2 NODAL 10q21.1-q22.2 nodal homolog (mouse) KIAA1274 10q22.1 nodal homolog (mouse) PRF1 10q22.2 perforin 1 (pore forming protein) ADAMTS14 10q21.3 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 14 C10orf27 10q22.2 chromosome 10 open reading frame 27 LOC338611 10q22.2 similar to 40S ribosomal protein S26 SGPL1 10q22 sphingosine-1-phosphate lyase 1 PCBD 10q22 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (TCF1) UNC5B 10q22.2 unc-5 homolog B (C. elegans) SLC29A3 10q22.2 solute carrier family 29 (nucleoside transporters), member 3 CDH23 10q22.3 cadherin related 23 PSAP 10q22.1 prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy) CHST3 10q22.1 carbohydrate (chondroitin 6) sulfotransferase 3 SPOCK2 10pter-q25.3 sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2 CGI-18 10pter-q25.3 CGI-18 protein LOC119504 10q22.2 hypothetical protein LOC119504 RTP801 DNAJB12 10q22.3 DnaJ (Hsp40) homolog, subfamily B, member 12 CBARA1 10q22.3 calcium binding atopy-related autoantigen 1 C10orf42 10q22.2 chromosome 10 open reading frame 42 FLJ39116 10q22.2-q22.3 oncoprotein induced transcript 3 PLA2G13 10q22.3 phospholipase A2, group XIII LOC148854 10q22.3 similar to 60S ribosomal protein L17 (L23) P4HA1 10q22.3 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide I NUDT13 10q22.3 nudix (nucleoside diphosphate linked moiety X)-type motif 13 HSGT1 10q22.3 nudix (nucleoside diphosphate linked moiety X)-type motif 13 DNAJC9 10q22.3 DnaJ (Hsp40) homolog, subfamily C, member 9 MRPS16 10q22.1 mitochondrial ribosomal protein S16 LOC118491 10q22.3 tetratricopeptide repeat-containing protein
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 2848 - 527 - 2009 19267410
    15 - 2845 - 526 - 2009 19267410
    14 - 2839 55 524 - 2009 19267410
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Endocrinethyroid   highly
    Hearing/Equilibriumearinnervestibulesacculehighly Mus musculus
     earinnervestibuleutricule  Mus musculus
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    fluid/secretion found to be expressed in other fluids of the body such as pancreatic juice, bile, cerebrospinal fluid, milk and seminal fluid
    at STAGE
  • polyfunctional protein, four homologous sphingolipid activator protein (SAPA, B, C, D) domains each of approximately 80 AAs
  • cysteine and proline residues, potential glycosylation sites
  • six cysteine residues, forming three disulfide bridges, that affect its structure and function
  • C terminal signal peptide, and the first half of the C-terminus contains a motif required for its binding to sortilin and its transport to the lysosomes
  • conjugated GlycoP
    mono polymer oligo
    isoforms Precursor precursor for 4 saposins A, B, C, and D
    interspecies homolog to murine Psap
    homolog to rattus psap
    CATEGORY enzyme , regulatory
        plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • synthesized as a 55 kDa protein in the endoplasmic reticulum, post-translationally modified to a 65 kDa glycosylated form and further glycosylated in the Golgi compartment to a 70 kDa product
  • basic FUNCTION
  • required for glucosylceramide degradation
  • required for degradation of some sphyngolipids with short carbohydrate chains
  • playing a role in the process of carcinogenesis or cancer progression in the prostate
  • playing a role in ceramide metabolism
  • saposin C required for normal resistance of acid beta-glucosidase to proteolytic degradation
  • indispensable cofactor for the intralysosomal degradation of a number of sphingolipids and seem to interact directly with the specific lipid hydrolases and/or facilitate presentation of the lipid substrates to these enzymes
  • non-essential enhancer for glucosylceramide degradation
  • has multiple roles in glycosphingolipid (GSL) catabolism as well as a prominent function in CNS and axonal integrity independent of its role as an optimizer/stabilizer of acid beta-glucosidase (Sun 2010)
  • essential role played in modulating the GCase (glucosylceramidase) function
  • plays an important role in the localization/interaction of the enzyme with the lysosomal membranes
  • important for normal adult cochlear innervation and the maintenance of normal hearing
  • plays likely a role not only in the maintenance of normal hearing but also an important role in the neuronal maturation processes of the vestibular sensory epithelium and the maintenance of normal vestibular system function
  • might likely enhance estrogen receptor alpha-mediated signaling axis and play a role in breast cancer development and progression
  • might play a crucial role in Gaucher disease-related Parkinson
  • is a precursor of four sphingolipid activator proteins (saposins A-D) that are essential for lysosomal hydrolysis of sphingolipids
  • epidermal PRSS3 and CASP14 work cooperatively in PSAP processing and they thereby contribute likely to permeability barrier formation
  • multifunctional protein that plays roles both intracellularly, as a regulator of lysosomal enzyme function, and extracellularly, as a secreted factor with neuroprotective and glioprotective effects
  • is not only a house keeping lysosomal protein but an essential factor in the development and maintenance of the nervous systems and other systems of the body
    metabolism lipid/lipoprotein
    a component
  • oligomerization of prosaposin is crucial for its entry into the secretory pathway
    small molecule
  • is a prominent endogenous UGGT1 substrate (UGGT1 may aid in the folding of sequential domain-containing proteins such as prosaposin)
  • GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and PSAP
  • PSAP a protein vital for GBA activity, protects GBA against SNCA inhibition
  • GPR37 and GPR37L1 have been shown to mediate signaling induced by both prosaposin and a fragment of PSAP known as prosaptide
  • facilitates sortilin-independent lysosomal trafficking of GRN
  • lysosomal enzyme cathepsin D (CTSD) mediates the proteolytic cleavage of PSAP precursor into saposins A-D 77)
  • role of GRN in PSAP lysosomal trafficking, suggesting that impaired lysosomal trafficking of PSAP is an underlying disease mechanism for NCL and FTLD due to GRN mutations
  • GRN and PSAP facilitate each other lysosomal trafficking, and interaction between GRN and PSAP is mediated by granulins and the linker region between saposin B and C
  • cell & other
    activated by proteolytic cleavage into four peptides
    corresponding disease(s) SAPC , SAPB , SAPA , SAPD
    related resource Tel-Aviv University Human Genetic Disease Database (Gaucher Disease)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    in cancer of the prostate, in progression
    constitutional     --low gain of function
    both PSAP reduction and overexpression lead to significantly elevated extracellular GRN levels
    tumoral     --over  
    in breast cancer cell lines
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • Psap deficiency in mice leads to severe Grn trafficking defects and a drastic increase in serum Pgrn levels