ACSL4

Chr X

acyl-CoA synthetase long chain family member 4

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

NCBI Gene: 2182ENSG00000068366UniProt: O60488

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. This isozyme preferentially utilizes arachidonate as substrate. The absence of this enzyme may contribute to the cognitive disability or Alport syndrome. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jan 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, X-linked 63
UniProtAMME complex

Clinical highlights

Gene-disease validity (ClinGen)
non-syndromic X-linked intellectual disability · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
1422
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.31
LOEUF· LoF intol.
LOF
Mechanism· G2P
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.31LOEUF
pLI 0.981
Z-score 4.11
OE 0.12 (0.05–0.31)
Highly constrained

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

Missense Constraint?
2.59Z-score
OE missense 0.55 (0.48–0.63)
143 obs / 260.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.12 (0.05–0.31)
0≤0.351.4
Missense OE?0.55 (0.48–0.63)
0≤0.61.4
Synonymous OE?0.99
0≤1.21.6
LoF obs/exp: 3 / 25.3Missense obs/exp: 143 / 260.7Syn Z: 0.07

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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