ACER2
Chr 9alkaline ceramidase 2
Also known as: ALKCDase2, ASAH3L
The ACER2 protein is a Golgi ceramidase that hydrolyzes ceramides into sphingosine and fatty acids, regulating the balance of bioactive sphingolipids that control cell proliferation, apoptosis, and autophagy. Mutations cause progressive leukodystrophy, which follows autosomal recessive inheritance and typically presents in early childhood with developmental regression and neurological deterioration. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.695), consistent with recessive disease where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
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
ACER2 · 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