PSAP Gene: Prosaposin - Function, Disease Associations, and Clinical Significance
Comprehensive guide to the PSAP gene, its protein product prosaposin, associated disorders, expression patterns, and mutations.
Gene Information Card
| Symbol | PSAP |
|---|---|
| Full Name | Prosaposin |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 5660 ncbi.nlm.nih.gov/gene/5660 |
| Ensembl ID | ENSG00000197746 |
| UniProt ID | P07602 |
| OMIM ID | 176801 |
| HGNC ID | 9498 |
| Aliases | GLBA, SAP1, SAP2, Saposin A, Saposin B, Saposin C, Saposin D |
Description
The PSAP gene encodes prosaposin, a precursor protein that is proteolytically cleaved into four functional sphingolipid activator proteins (SAPs): saposins A, B, C, and D. These saposins are essential for the lysosomal degradation of glycosphingolipids. Saposin A is required for galactocerebrosidase activity, saposin B acts as a cofactor for arylsulfatase A, saposin C stimulates glucocerebrosidase, and saposin D is involved in ceramide degradation. Mutations in PSAP can lead to various lysosomal storage disorders, including Gaucher disease, metachromatic leukodystrophy, and combined saposin deficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gaucher Disease (variant) | Mutations in the saposin C domain of PSAP impair the activation of glucocerebrosidase, leading to the accumulation of glucosylceramide in macrophages. | OMIM #610539; Multiple case reports |
| Metachromatic Leukodystrophy (variant) | Mutations in the saposin B domain of PSAP impair the function of arylsulfatase A, leading to the accumulation of sulfatides in the nervous system. | OMIM #249900; Case reports |
| Combined Saposin Deficiency | Mutations that prevent the processing of prosaposin into all four saposins, leading to a severe, early-onset form of lysosomal storage disease with features of Gaucher, Fabry, and metachromatic leukodystrophy. | OMIM #611721; Case reports |
| Krabbe Disease (variant) | Mutations in the saposin A domain of PSAP impair galactocerebrosidase activity, leading to the accumulation of galactosylceramide and psychosine. | OMIM #611722; Case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 39.0 | High |
| Kidney | 35.0 | High |
| Liver | 30.0 | High |
| Lung | 25.0 | Medium |
| Heart | 20.0 | Medium |
| Spleen | 18.0 | Medium |
| Testis | 15.0 | Medium |
| Pancreas | 10.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | 45.0 | High expression |
| A549 (Lung) | 30.0 | Moderate expression |
| MCF7 (Breast) | 25.0 | Moderate expression |
| K562 (Leukemia) | 20.0 | Moderate expression |
| HeLa (Cervical) | 15.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.577C>T (p.Arg193Ter) | Nonsense | Rare | Premature stop codon leading to loss of saposin B and C function. |
| c.802G>A (p.Gly268Ser) | Missense | Rare | Affects saposin C domain, reducing glucocerebrosidase activation. |
| c.1129C>T (p.Arg377Ter) | Nonsense | Rare | Premature stop codon leading to loss of saposin D function. |
| c.155C>T (p.Pro52Leu) | Missense | Rare | Affects saposin A domain, impairing galactocerebrosidase activation. |
| c.1A>G (p.Met1?) | Start codon loss | Rare | Loss of translation initiation, leading to complete loss of prosaposin. |
Mutation functional classification
Loss of Function (LOF)
Most PSAP mutations are loss-of-function, leading to reduced or absent saposin activity. This results in the accumulation of specific glycosphingolipids in lysosomes, causing cellular toxicity and tissue damage.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PSAP.
Dominant Negative (DN)
PSAP mutations are typically inherited in an autosomal recessive manner. A dominant-negative effect is not a common mechanism for PSAP-related disorders.
View complete mutation data：
Gene Ontology (GO)
| • sphingolipid activator protein activity | • lipid binding |
| • enzyme activator activity | • lysosome |
| • extracellular space | • endoplasmic reticulum |
| • Golgi apparatus | • sphingolipid metabolic process |
| • glycosphingolipid metabolic process | • lysosomal lumen |
Pathways
• Sphingolipid metabolism
• Glycosphingolipid metabolism
• Lysosome
Protein Summary
Prosaposin is a 524-amino acid glycoprotein that is synthesized in the endoplasmic reticulum and processed in the Golgi apparatus. It is secreted as a full-length protein or targeted to lysosomes where it is cleaved into four saposins (A, B, C, D). Each saposin is a small, heat-stable protein with a conserved saposin domain. Saposins are essential cofactors for specific lysosomal hydrolases, facilitating the degradation of glycosphingolipids. Prosaposin also has neurotrophic and neuroprotective functions, independent of its role as a saposin precursor.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSAP Knockout HEK293 Cell Line | EDJ-KQ2673 | Human | 5660 | Details Get a Quote |
| PRPSAP1 Knockout HEK293 Cell Line | EDJ-KQ5549 | Human | 5635 | Details Get a Quote |
| PRPSAP2 Knockout HEK293 Cell Line | EDJ-KQ5554 | Human | 5636 | Details Get a Quote |
| PSAPL1 Knockout HEK293 Cell Line | EDJ-KQ14946 | Human | 768239 | Details Get a Quote |
| PSAP Knockout A-549 Cell Line | EDJ-KQ24854 | Human | 5660 | Details Get a Quote |
| PSAP Knockout HCT 116 Cell Line | EDJ-KQ24856 | Human | 5660 | Details Get a Quote |
| PSAP Knockout HeLa Cell Line | EDJ-KQ24857 | Human | 5660 | Details Get a Quote |
| PRPSAP1 Knockout HCT 116 Cell Line | EDJ-KQ27558 | Human | 5635 | Details Get a Quote |
| PRPSAP1 Knockout A-549 Cell Line | EDJ-KQ28810 | Human | 5635 | Details Get a Quote |
| PRPSAP1 Knockout HeLa Cell Line | EDJ-KQ28812 | Human | 5635 | Details Get a Quote |
| PRPSAP2 Knockout A-549 Cell Line | EDJ-KQ28819 | Human | 5636 | Details Get a Quote |
| PRPSAP2 Knockout HCT 116 Cell Line | EDJ-KQ28820 | Human | 5636 | Details Get a Quote |
| PRPSAP2 Knockout HeLa Cell Line | EDJ-KQ28821 | Human | 5636 | Details Get a Quote |
| PSAPL1 Knockout HeLa Cell Line | EDJ-KQ60782 | Human | 768239 | Details Get a Quote |
| PSAPL1 Knockout A-549 Cell Line | EDJ-KQ69251 | Human | 768239 | Details Get a Quote |
Displaying Records 1 To 15 Of 16 Records
