ACSL4

Chr Xq23

acyl-CoA synthetase long chain family member 4

Aliases:: ACS4, LACS4
MANE:: ENST00000672401.1

OMIM: 300157 ↗NCBI: 2182 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

ACSL4 · O60488

v62025-08-01

Predicted Aligned Error matrix for ACSL4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

90.4/ 100

Very high

711 residues

Confidence breakdown

Very high(≥ 90)66%
Confident(70–90)30%
Low(50–70)3%
Very low(< 50)1%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mitochondrial disorders
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Disease associations (Open Targets)

X-linked non-syndromic intellectual disability
0.73
neurodegenerative disease
0.54
Alport syndrome - intellectual disability - midface hypoplasia - elliptocytosis
0.51
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
0.51
non-syndromic X-linked intellectual disability
0.48
Alzheimer disease
0.38
Parkinson disease
0.38
multiple sclerosis
0.37
lysosomal storage disease
0.37
Intellectual disability
0.31

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Long-chain-fatty-acid--CoA ligase 4

Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:21242590, PubMed:22633490, PubMed:24269233, PubMed:31061331, PubMed:38720107). Preferentially activates arachidonate and eicosapentaenoate as substrates (PubMed:21242590). Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET (PubMed:21242590). Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion (PubMed:21242590). Acts as an activator of ferroptosis by activating polyunsaturated fatty acids, especially arachidonate and adrenate, to their active form, generating the primary lipid-peroxidation substrates that contribute to ferroptosis (PubMed:27842070, PubMed:35027735, PubMed:38720107)