SPTLC1
Chr 9ADserine palmitoyltransferase long chain base subunit 1
Also known as: ALS27, HSAN1, HSN1, LBC1, LCB1, SPT1, SPTI
The protein is the long chain base subunit 1 of serine palmitoyltransferase, which catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine with activated acyl-CoA. Mutations cause hereditary sensory and autonomic neuropathy type IA and juvenile amyotrophic lateral sclerosis, both inherited in an autosomal dominant pattern. The gene shows very low constraint against loss-of-function variants (pLI near 0), suggesting the pathogenic variants likely affect protein function through other mechanisms.
Definitive — sufficient evidence for diagnostic panels
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SPTLC1 · 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