ACSL1

Chr 4

acyl-CoA synthetase long chain family member 1

Also known as: ACS1, FACL1, FACL2, LACS, LACS1, LACS2

NCBI Gene: 2180ENSG00000151726UniProt: P33121

The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

Research Assistant →
0
Active trials
130
Pubs (1 yr)
105
P/LP submissions
0%
P/LP missense
0.48
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ACSL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
105 unique Pathogenic / Likely Pathogenic· 77 VUS of 216 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.002
Z-score 4.37
OE 0.30 (0.20–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.40Z-score
OE missense 0.80 (0.73–0.88)
330 obs / 410.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.20–0.48)
0≤0.351.4
Missense OE0.80 (0.73–0.88)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 14 / 46.0Missense obs/exp: 330 / 410.0Syn Z: 0.44
DN
0.6939th %ile
GOF
0.6344th %ile
LOF
0.3066th %ile

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.

DNprediction above median
GOFprediction above median

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

216 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic9
VUS77
Likely Benign11
Benign3
96
Pathogenic
9
Likely Pathogenic
77
VUS
11
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
0
9
0
9
VUS
0
64
13
0
77
Likely Benign
0
9
1
1
11
Benign
0
0
0
3
3
Total0731194196

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

View in ClinVar →

Protein Context — Lollipop Plot

ACSL1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Disposable Plastic-Alcohol Leachates as Emerging Neurotoxicants: Evidence for the miR-330-3p/Acsl1 Pathway in Cognitive Performance.
Zhang J et al.·Environ Res
2026
Identification of plasma inflammatory biomarkers for Alzheimer's disease reveals IFN-γ as a regulator of ACSL1-mediated microglia phenotype.
Huang R et al.·Front Immunol
2026Open Access
ACSL1-Dependent Microglial Lipoimmunometabolic Reprogramming Underlies Cognitive Deficits in Alcohol Use Disorder.
Hao L et al.·Adv Sci (Weinh)
2026
Dysregulation of miR-140-3p is involved in the pathogenesis of pulpitis via the regulation of ACSL1.
Li S et al.·Odontology
2026
Myricanol modulates PPARγ/ACSL1/SCD1 metabolic signaling pathway to promote mitochondria biogenesis and fatty acid β-oxidation in high-fat diet-induced obese mice.
Zhang X et al.·J Ethnopharmacol
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients