CERS1
Chr 19ARceramide synthase 1
Also known as: EPM8, LAG1, LASS1, UOG1
The ceramide synthase enzyme catalyzes the synthesis of C18 ceramide from acyl-CoA and sphingoid bases, playing a critical role in cerebellar development and Purkinje cell function in the brain. Autosomal recessive mutations cause progressive myoclonic epilepsy type 8, a neurodegenerative disorder involving seizures and dementia. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.692), reflecting its importance in neuronal function.
Moderate evidence — consider for supplementary testing
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CERS1 · 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