SPNS1
Chr 16SPNS lysolipid transporter 1, lysophospholipid
Also known as: HSpin1, LAT, PP2030, SLC62A1, SLC63A1, SPIN1, SPINL, nrs
SPNS1 encodes a lysosomal membrane transporter that mediates the efflux of lysophospholipids from lysosomes to the cytosol, playing a critical role in phospholipid salvage pathways and lysosomal homeostasis. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.596), and the associated neurological phenotype reflects the essential role of lysosomal phospholipid metabolism in brain development and function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function 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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SPNS1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools