ACSL1

Chr 4

acyl-CoA synthetase long chain family member 1

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

NCBI Gene: 2180 ENSG00000151726 UniProt: P33121 OMIM: 152425

ACSL1 encodes acyl-CoA synthetase long chain family member 1, which catalyzes the conversion of long-chain fatty acids to acyl-CoAs for lipid synthesis and beta-oxidation, with preference for palmitoleate, oleate, and linoleate. The gene is not highly constrained (pLI 0.002, LOEUF 0.476), and no established human disease associations are currently documented in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.48

Clinical Summary— ACSL1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

65 VUS of 98 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 OE?0.30 (0.20–0.48)

0≤0.351.4

Missense OE?0.80 (0.73–0.88)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 14 / 46.0Missense obs/exp: 330 / 410.0Syn Z: 0.44

This gene — mechanism propensity

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

98 submitted variants in ClinVar

ClinVar

Classification Summary

VUS65

Likely Benign10

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	65	0	65
Likely Benign	9	1	10
Benign	0	3	3
Total	74	4	78

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

View in ClinVar →

108 pathogenic / likely-pathogenic (of 122) ClinVar copy-number / structural variants overlap ACSL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →