ACSM4
Chr 12acyl-CoA synthetase medium chain family member 4
ACSM4 encodes a mitochondrial enzyme that activates medium-chain fatty acids (C6-12) by conjugating them with coenzyme A, representing the first step in fatty acid metabolism. The gene shows very low constraint against loss-of-function variants, and no definitive disease associations have been established in humans. Clinical significance of ACSM4 variants remains unclear at this time.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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
130 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 | 43 | 0 | 43 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 66 | 9 | 0 | 75 |
Likely Benign | 0 | 3 | 0 | 1 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 69 | 54 | 1 | 124 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ACSM4 · 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