SGPL1: Sphingosine-1-Phosphate Lyase 1
Key enzyme in sphingolipid metabolism, associated with nephrotic syndrome and primary adrenal insufficiency
Gene Information Card
| Symbol | SGPL1 |
|---|---|
| Full Name | Sphingosine-1-Phosphate Lyase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 8879 ncbi.nlm.nih.gov/gene/8879 |
| Ensembl ID | ENSG00000166224 |
| UniProt ID | O95470 |
| OMIM ID | 603729 |
| HGNC ID | 10817 |
| Aliases | SPL, S1PL, hSPL, S1P lyase |
Description
SGPL1 encodes sphingosine-1-phosphate lyase 1, an enzyme that catalyzes the irreversible cleavage of sphingosine-1-phosphate (S1P) into phosphoethanolamine and hexadecenal, a key step in sphingolipid degradation. This enzyme regulates cellular S1P levels, influencing cell survival, migration, and immune function. Loss-of-function mutations cause SGPL1 deficiency (sphingolipidosis), leading to nephrotic syndrome, primary adrenal insufficiency, and neurological abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nephrotic syndrome type 14 (NPHS14) | Loss-of-function mutations impair S1P degradation, causing S1P accumulation and podocyte dysfunction | OMIM #617575; ClinVar |
| Primary adrenal insufficiency (SGPL1 deficiency) | Disrupted sphingolipid metabolism leads to adrenal cortex cell death | OMIM #617575; ClinVar |
| Sphingolipidosis with neurological involvement | Accumulation of sphingolipids in neural tissue due to enzyme deficiency | OMIM #603729; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 9.8 | High |
| Adrenal gland | 8.2 | High |
| Small intestine | 6.4 | Medium |
| Brain | 4.1 | Medium |
| Heart | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HepG2 | 11.0 | High expression |
| A549 | 7.8 | Medium expression |
| K562 | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.665G>A (p.Arg222Gln) | Missense | Rare | Loss of function; associated with nephrotic syndrome |
| c.1045C>T (p.Arg349*) | Nonsense | Rare | Premature stop; loss of function; adrenal insufficiency |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein production; severe phenotype |
| c.1274_1275del (p.Glu425Glyfs*2) | Frameshift | Rare | Loss of function; neurological involvement |
Mutation functional classification
Loss of Function (LOF)
Most reported SGPL1 mutations are loss-of-function, leading to reduced or absent enzyme activity and S1P accumulation.
Gain of Function (GOF)
No gain-of-function mutations have been reported in SGPL1.
Dominant Negative (DN)
No dominant-negative mutations have been described; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Sphingolipid metabolism (KEGG: hsa00600)
• Sphingosine-1-phosphate signaling (Reactome: R-HSA-428157)
Protein Summary
SGPL1 encodes a 568-amino acid protein localized to the endoplasmic reticulum. It is a pyridoxal phosphate-dependent lyase that cleaves sphingosine-1-phosphate, a bioactive lipid that regulates cell proliferation, migration, and immune responses. The enzyme is critical for maintaining sphingolipid homeostasis. Deficiency leads to accumulation of S1P and related sphingolipids, causing multi-organ pathology primarily affecting kidneys, adrenal glands, and nervous system.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SGPL1 Knockout HEK293 Cell Line | EDJ-KQ1755 | Human | 8879 | Details Get a Quote |
| SGPL1 Knockout A-549 Cell Line | EDJ-KQ21629 | Human | 8879 | Details Get a Quote |
| SGPL1 Knockout HCT 116 Cell Line | EDJ-KQ21630 | Human | 8879 | Details Get a Quote |
| SGPL1 Knockout HeLa Cell Line | EDJ-KQ21631 | Human | 8879 | Details Get a Quote |
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