SGPP2
Chr 2sphingosine-1-phosphate phosphatase 2
Also known as: SPP2, SPPase2
The protein is a sphingosine-1-phosphate phosphatase that degrades the bioactive signaling molecule sphingosine-1-phosphate, regulating sphingolipid metabolism and inflammatory signaling pathways. Mutations cause autosomal recessive spastic paraplegia with onset typically in childhood or adolescence, characterized by progressive lower limb spasticity and weakness. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
92 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 31 | 0 | 31 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 50 | 2 | 0 | 52 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 54 | 34 | 0 | 88 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SGPP2 · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools