SGPL1
Chr 10ARsphingosine-1-phosphate lyase 1
Also known as: NPHS14, RENI, S1PL, SPL
The protein cleaves sphingosine-1-phosphate into fatty aldehydes and phosphoethanolamine, playing a critical role in sphingolipid metabolism, lipid homeostasis, and neuronal autophagy regulation. Mutations cause RENI syndrome, an autosomal recessive disorder characterized by renal involvement (nephrotic syndrome) and neurological manifestations. The gene shows high constraint against loss-of-function variants (LOEUF 0.554), reflecting its essential cellular functions.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SGPL1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools