PSAP
prosaposin, the group of Receptor ligands
Basic information
Region (hg38): 10:71816298-71851251
Previous symbols: [ "SAP1", "GLBA", "SAP2" ]
Links
Phenotypes
GenCC
Source:
- Krabbe disease due to saposin A deficiency (Definitive), mode of inheritance: AR
- Krabbe disease due to saposin A deficiency (Strong), mode of inheritance: AR
- combined PSAP deficiency (Strong), mode of inheritance: AR
- Gaucher disease due to saposin C deficiency (Strong), mode of inheritance: AR
- metachromatic leukodystrophy due to saposin B deficiency (Strong), mode of inheritance: AR
- Gaucher disease due to saposin C deficiency (Moderate), mode of inheritance: AR
- metachromatic leukodystrophy due to saposin B deficiency (Moderate), mode of inheritance: AR
- combined PSAP deficiency (Supportive), mode of inheritance: AR
- Parkinson disease 24, autosomal dominant, susceptibility to (Limited), mode of inheritance: Unknown
- combined PSAP deficiency (Strong), mode of inheritance: AR
- Gaucher disease due to saposin C deficiency (Strong), mode of inheritance: AR
- Krabbe disease due to saposin A deficiency (Limited), mode of inheritance: AR
- metachromatic leukodystrophy due to saposin B deficiency (Strong), mode of inheritance: AR
- metachromatic leukodystrophy due to saposin B deficiency (Definitive), mode of inheritance: AR
- Krabbe disease due to saposin A deficiency (Moderate), mode of inheritance: AR
- Gaucher disease due to saposin C deficiency (Definitive), mode of inheritance: AR
- combined PSAP deficiency (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Parkinson disease 24, autosomal dominant, susceptibility to | AD | Neurologic | Individuals with Parkinson disease may respond to levodopa | Biochemical; Gastrointestinal; Musculoskeletal; Neurologic | 41211; 6126151; 2060627; 3024666; 2615292; 2514102; 2764035; 1371116; 8460394; 8554069; 9672525; 9930900; 10682309; 11309366; 15856305; 15773042; 17919309; 19267410; 19955343; 20484222; 22652185 |
| BMT has been described for some allelic conditions; The evidence of the association of variants with Parkinson disease is unclear |
ClinVar
This is a list of variants' phenotypes submitted to
- Sphingolipid_activator_protein_1_deficiency (765 variants)
- Metachromatic_leukodystrophy (118 variants)
- not_provided (86 variants)
- Inborn_genetic_diseases (78 variants)
- Combined_PSAP_deficiency (75 variants)
- Gaucher_disease_due_to_saposin_C_deficiency (63 variants)
- Krabbe_disease_due_to_saposin_A_deficiency (62 variants)
- Parkinson_disease_24,_autosomal_dominant,_susceptibility_to (27 variants)
- PSAP-related_disorder (22 variants)
- not_specified (11 variants)
- Galactosylceramide_beta-galactosidase_deficiency (6 variants)
- Atypical_Gaucher_Disease (3 variants)
- Neuromuscular_disease (2 variants)
- Parkinson_disease,_late-onset (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSAP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002778.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | 252 | 269 | |||
| missense | 10 | 257 | 17 | 291 | ||
| nonsense | 11 | 16 | ||||
| start loss | 2 | 1 | 3 | |||
| frameshift | 18 | 24 | ||||
| splice donor/acceptor (+/-2bp) | 24 | 32 | ||||
| Total | 39 | 46 | 275 | 269 | 6 |
Highest pathogenic variant AF is 0.000037174446
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PSAP | protein_coding | protein_coding | ENST00000394936 | 14 | 35072 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.991 | 0.00949 | 125739 | 0 | 9 | 125748 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.525 | 314 | 289 | 1.09 | 0.0000176 | 3458 |
| Missense in Polyphen | 72 | 82.713 | 0.87048 | 1083 | ||
| Synonymous | -1.34 | 137 | 118 | 1.16 | 0.00000847 | 991 |
| Loss of Function | 4.30 | 3 | 27.2 | 0.110 | 0.00000121 | 343 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000185 | 0.000185 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000529 | 0.0000527 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.; FUNCTION: Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).; FUNCTION: Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.;
- Disease
- DISEASE: Combined saposin deficiency (CSAPD) [MIM:611721]: Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement. {ECO:0000269|PubMed:11309366, ECO:0000269|PubMed:1371116}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leukodystrophy metachromatic due to saposin-B deficiency (MLD-SAPB) [MIM:249900]: An atypical form of metachromatic leukodystrophy. It is characterized by tissue accumulation of cerebroside-3-sulfate, demyelination, periventricular white matter abnormalities, peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotor regression, seizures, cognitive decline and spastic quadriparesis. {ECO:0000269|PubMed:10196694, ECO:0000269|PubMed:10682309, ECO:0000269|PubMed:2019586, ECO:0000269|PubMed:2302219, ECO:0000269|PubMed:2320574}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Gaucher disease, atypical, due to saposin C deficiency (AGD) [MIM:610539]: A disease characterized by marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease. Gaucher disease is a lysosomal storage disorder characterized by skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement. {ECO:0000269|PubMed:17919309, ECO:0000269|PubMed:2060627}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Krabbe disease, atypical, due to saposin A deficiency (AKRD) [MIM:611722]: A disorder of galactosylceramide metabolism. Clinical features include neurologic regression around age 3 months, loss of spontaneous movements, hyporeflexia, generalized brain atrophy, and diffuse white matter dysmyelination. {ECO:0000269|PubMed:15773042}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).;
- Pathway
- Lysosome - Homo sapiens (human);Signaling by GPCR;Neutrophil degranulation;Signal Transduction;Metabolism of lipids;Innate Immune System;Immune System;Metabolism;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis;G alpha (i) signalling events;Glycosphingolipid metabolism;Sphingolipid metabolism;GPCR downstream signalling
(Consensus)
Recessive Scores
- pRec
- 0.406
Intolerance Scores
- loftool
- 0.0907
- rvis_EVS
- -1
- rvis_percentile_EVS
- 8.47
Haploinsufficiency Scores
- pHI
- 0.201
- hipred
- Y
- hipred_score
- 0.594
- ghis
- 0.556
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.855
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Psap
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype;
Gene ontology
- Biological process
- platelet degranulation;corneocyte development;galactosylceramide catabolic process;glycosphingolipid metabolic process;lipid transport;G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;sensory perception of sound;regulation of autophagy;regulation of lipid metabolic process;myelination;neutrophil degranulation;positive regulation of MAPK cascade;neuromuscular process controlling balance;positive regulation of hydrolase activity;micturition;prostate gland growth;epithelial cell differentiation involved in prostate gland development;cellular response to organic substance;cochlea development;walking behavior;negative regulation of hydrogen peroxide-induced cell death;cornified envelope assembly;ganglioside GM1 transport to membrane
- Cellular component
- extracellular region;extracellular space;lysosome;lysosomal membrane;plasma membrane;azurophil granule membrane;lysosomal lumen;intracellular membrane-bounded organelle;collagen-containing extracellular matrix;extracellular exosome
- Molecular function
- G protein-coupled receptor binding;beta-galactosidase activity;protein binding;phospholipid binding;enzyme activator activity;lipid binding;protein homodimerization activity;ganglioside GM1 binding;ganglioside GM2 binding;ganglioside GM3 binding;ganglioside GT1b binding;ganglioside GP1c binding