ACSL6

Chr 5

acyl-CoA synthetase long chain family member 6

Also known as: ACS2, FACL6, LACS 6, LACS2, LACS5

NCBI Gene: 23305ENSG00000164398UniProt: Q9UKU0

The protein encoded by this gene catalyzes the formation of acyl-CoA from fatty acids, ATP, and CoA, using magnesium as a cofactor. The encoded protein plays a major role in fatty acid metabolism in the brain. Translocations with the ETV6 gene are causes of myelodysplastic syndrome with basophilia, acute myelogenous leukemia with eosinophilia, and acute eosinophilic leukemia. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2011]

101
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ACSL6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 73 VUS of 101 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.47LOEUF
pLI 0.003
Z-score 4.29
OE 0.30 (0.19–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.76Z-score
OE missense 0.76 (0.69–0.83)
321 obs / 422.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.19–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.69–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 13 / 43.5Missense obs/exp: 321 / 422.7Syn Z: -1.23

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS73
Likely Benign8
Benign4
14
Pathogenic
2
Likely Pathogenic
73
VUS
8
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
71
2
0
73
Likely Benign
0
3
1
4
8
Benign
0
0
2
2
4
Total074216101

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ACSL6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ACSL family: The regulatory mechanisms and therapeutic implications in cancer.
Quan J et al.·Eur J Pharmacol
2021Review
ETV6::ACSL6 translocation-driven super-enhancer activation leads to eosinophilia in acute lymphoblastic leukemia through IL-3 overexpression.
Xu W et al.·Haematologica
2024
Blocking ACSL6 Compromises Autophagy via FLI1-Mediated Downregulation of COLs to Radiosensitize Lung Cancer.
Ding W et al.·Adv Sci (Weinh)
2024
Myeloid neoplasm with ETV6::ACSl6 fusion: landscape of molecular and clinical features.
Su Z et al.·Hematology
2022Review
ETV6-ACSL6 fusion gene in myeloid neoplasms: clinical spectrum, current practice, and outcomes.
Wu X et al.·Orphanet J Rare Dis
2020
Increased ACSL6 Expression Predicts a Favorable Prognosis in Triple-negative Breast Cancer.
Hua H et al.·Curr Med Chem
2025
Imatinib-Induced Clinical Response in ETV6::ACSL6 Myeloid Neoplasm with Eosinophilic Pneumonitis: A Case Report.
Hoff FW et al.·Am J Case Rep
2025Case report
The therapeutic and biomarker significance of ferroptosis in chronic myeloid leukemia.
Zhong F et al.·Front Immunol
2024
Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets.
Deng X et al.·Mol Biomed
2025Review
NSUN2 knockdown ameliorates hepatic glucose and lipid metabolism disorders in type 2 diabetes mellitus through the Inhibition of ACSL6 m5C methylation.
Jiang X et al.·Lipids Health Dis
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools