SGPL1

Chr 10AR

sphingosine-1-phosphate lyase 1

Also known as: NPHS14, RENI, S1PL, SPL

NCBI Gene: 8879 ENSG00000166224 UniProt: O95470 OMIM: 603729

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in RENI syndrome. [provided by Alliance of Genome Resources, Jun 2026]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

RENI syndromeMIM #617575

Clinical highlights

Gene-disease validity (ClinGen)

nephrotic syndrome 14 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.55

LOEUF

Mechanism· predicted

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GeneReview available — SGPL1