ACSL4

Chr XXLD

acyl-CoA synthetase long chain family member 4

Also known as: ACS4, FACL4, LACS4, MRX63, MRX68, XLID63

The ACSL4 protein converts long-chain fatty acids (particularly arachidonate) to acyl-CoA esters for lipid biosynthesis and fatty acid degradation, and plays a role in insulin secretion and ferroptosis regulation. Mutations cause X-linked intellectual disability and may contribute to Alport syndrome with sensorineural hearing loss. This gene shows high constraint against loss-of-function variants, indicating that complete loss of protein function is likely deleterious.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismXLDLOEUF 0.311 OMIM phenotype
Clinical SummaryACSL4
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Gene-Disease Validity (ClinGen)
non-syndromic X-linked intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.981
Z-score 4.11
OE 0.12 (0.050.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.59Z-score
OE missense 0.55 (0.480.63)
143 obs / 260.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.12 (0.050.31)
00.351.4
Missense OE0.55 (0.480.63)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 3 / 25.3Missense obs/exp: 143 / 260.7Syn Z: 0.07

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ACSL4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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