PSAP

Chr 10

prosaposin

Also known as: GLBA, PARK24, PSAPD, SAP1, SAP2

NCBI Gene: 5660ENSG00000197746UniProt: Q9NZJ7

This gene encodes a highly conserved preproprotein that is proteolytically processed to generate four main cleavage products including saposins A, B, C, and D. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. Mutations in this gene have been associated with Gaucher disease and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

GeneReviewsResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)
metachromatic leukodystrophy due to saposin B deficiency · ARDefinitivesufficient evidence for diagnostic panels4 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
104
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.28
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — PSAP
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.28LOEUF
pLI 0.991
Z-score 4.30
OE 0.11 (0.05–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
-0.52Z-score
OE missense 1.09 (0.99–1.19)
314 obs / 288.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.11 (0.05–0.28)
0≤0.351.4
Missense OE?1.09 (0.99–1.19)
0≤0.61.4
Synonymous OE?1.16
0≤1.21.6
LoF obs/exp: 3 / 27.2Missense obs/exp: 314 / 288.9Syn Z: -1.34

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PSAP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients