ACSL3
Chr 2acyl-CoA synthetase long chain family member 3
Also known as: ACS3, FACL3, LACS 3, LACS3, PRO2194
ACSL3 encodes a long-chain fatty-acid-coenzyme A ligase that converts free fatty acids into fatty acyl-CoA esters for lipid biosynthesis and fatty acid degradation, with high expression in brain and preference for substrates including myristate and arachidonate. Mutations cause autosomal recessive intellectual disability with onset in infancy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.55), consistent with its role in brain lipid metabolism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
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
125 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 31 | 0 | 31 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 62 | 1 | 0 | 63 |
Likely Benign | 0 | 4 | 0 | 1 | 5 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 0 | 66 | 33 | 3 | 102 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ACSL3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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