ACSL4

Summary

ACSL4 (acyl-CoA synthetase long chain family member 4, HGNC:3571) is a protein-coding gene on chromosome Xq23, encoding Long-chain-fatty-acid–CoA ligase 4 (O60488). 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.

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.

Source: NCBI Gene 2182 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-syndromic X-linked intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 367 total — 24 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001318510

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3571
Approved symbol	ACSL4
Name	acyl-CoA synthetase long chain family member 4
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	ACS4, LACS4
Ensembl gene	ENSG00000068366
Ensembl biotype	protein_coding
OMIM	300157
Entrez	2182

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 24 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000340800, ENST00000348502, ENST00000439581, ENST00000469796, ENST00000502391, ENST00000504383, ENST00000505075, ENST00000505855, ENST00000508092, ENST00000514500, ENST00000671846, ENST00000672282, ENST00000672401, ENST00000673016, ENST00000682031, ENST00000683559, ENST00000684030, ENST00000684414, ENST00000851255, ENST00000851256, ENST00000851257, ENST00000851258, ENST00000915898, ENST00000915899, ENST00000915900, ENST00000953314, ENST00000953315, ENST00000953316, ENST00000953317, ENST00000953318, ENST00000953319

RefSeq mRNA: 4 — MANE Select: NM_001318510 NM_001318509, NM_001318510, NM_004458, NM_022977

CCDS: CCDS14548, CCDS14549

Canonical transcript exons

ENST00000672401 — 16 exons

Exon	Start	End
ENSE00000674526	109669034	109669173
ENSE00000674527	109668101	109668273
ENSE00000674528	109665420	109665494
ENSE00000674532	109659354	109659511
ENSE00000895425	109677988	109678111
ENSE00000895428	109678265	109678415
ENSE00000895431	109680998	109681136
ENSE00000895440	109681266	109681375
ENSE00000895444	109682719	109682896
ENSE00000979252	109674402	109674473
ENSE00000979255	109663211	109663402
ENSE00001159638	109696144	109696196
ENSE00001699022	109661531	109661645
ENSE00002053298	109683136	109683375
ENSE00003892017	109641335	109644186
ENSE00003893060	109733139	109733257

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 97.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.1970 / max 6809.8709, expressed in 1746 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200131	53.8063	1727
200130	11.4606	1626
200132	10.9589	1646
200135	0.2600	23
200134	0.2580	101
200133	0.2306	95
200136	0.1386	18
200137	0.0840	10

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.41	gold quality
monocyte	CL:0000576	94.73	gold quality
mononuclear cell	CL:0000842	94.25	gold quality
colonic epithelium	UBERON:0000397	94.08	gold quality
leukocyte	CL:0000738	93.91	gold quality
cortical plate	UBERON:0005343	93.60	gold quality
calcaneal tendon	UBERON:0003701	93.00	gold quality
right adrenal gland	UBERON:0001233	92.98	gold quality
adrenal gland	UBERON:0002369	92.63	gold quality
left adrenal gland	UBERON:0001234	92.60	gold quality
right adrenal gland cortex	UBERON:0035827	92.40	gold quality
islet of Langerhans	UBERON:0000006	92.37	gold quality
gall bladder	UBERON:0002110	92.18	gold quality
left adrenal gland cortex	UBERON:0035825	92.14	gold quality
adrenal cortex	UBERON:0001235	91.76	gold quality
right lung	UBERON:0002167	91.21	gold quality
omental fat pad	UBERON:0010414	90.91	gold quality
peritoneum	UBERON:0002358	90.86	gold quality
upper lobe of left lung	UBERON:0008952	90.86	gold quality
upper lobe of lung	UBERON:0008948	90.79	gold quality
stromal cell of endometrium	CL:0002255	90.42	gold quality
lower lobe of lung	UBERON:0008949	90.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.94	gold quality
vermiform appendix	UBERON:0001154	89.08	gold quality
pericardium	UBERON:0002407	88.95	gold quality
prefrontal cortex	UBERON:0000451	88.76	gold quality
gastrocnemius	UBERON:0001388	88.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.32	gold quality
left coronary artery	UBERON:0001626	88.26	gold quality
metanephros cortex	UBERON:0010533	88.15	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	743.86
E-CURD-119	yes	48.57
E-CURD-88	yes	25.52
E-ANND-3	yes	18.90
E-GEOD-130148	yes	14.10
E-CURD-112	yes	13.85
E-MTAB-9067	yes	13.28
E-CURD-122	yes	11.32
E-MTAB-9801	yes	7.58
E-HCAD-10	yes	6.81
E-GEOD-135922	yes	6.50
E-CURD-46	yes	5.75
E-MTAB-5061	yes	4.04
E-MTAB-6142	no	138.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, MYC, SP1, TCF3

miRNA regulators (miRDB)

261 targeting ACSL4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Fatty acid CoA ligase 4 is up-regulated in colon adenocarcinoma. (PMID:11731423)
• FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation (PMID:11889465)
• FACL4 is highly expressed in hippocampal and cerebellar neurons and may have a role in X linked mental retardation. (PMID:12525535)
• Overexpression of Fatty acid-CoA ligase 4 is associated with human hepatocellular carcinoma (PMID:12824887)
• FACL4 is involved in the hepatocellular carcinoma tumorigenesis and both cAMP and p38 MAPK pathways are associated with the regulation of FACL4 (PMID:15849811)
• Disruption of DMD and the absence of ACSL4 in a patient are responsible for neuromuscular disease and cognitive impairment. (PMID:16276108)
• FACL4 affects HCC cell growth and suggest that modulation of FACL4 expression/activity is an approach for treatment of HCC. (PMID:17934335)
• FACL4 might play a role in the growth of hepatic cancer cells. (PMID:18059177)
• No association between polymorphisms in the FACL4 (fatty acid-CoA ligase 4) gene and nonspecific mental retardation in Qin-Ba mountain region of China. (PMID:18614287)
• The common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered Fatty Acid composition of plasma phosphatidylcholines in patients with metabolic syndrome . (PMID:19346733)
• ACSL4 can substitute the functions of dAcsl(l(2)44DEa in organismal viability, lipid storage and the neural wiring in visual center. (PMID:19617635)
• This study found no significant relationship between FACL4 and cognitive function. (PMID:20452052)
• Data suggest that the development of combinatory therapies that profit from the ACSL4, lipooxygenase and COX-2 synergistic action may allow for lower medication doses and avoidance of side effects. (PMID:21085606)
• CSL4 modulates PGE release from human erial smooth muscle cells. (PMID:21242590)
• A total of six novel and 11 known single nucleotide polymorphisms were identified. Further studies are warranted to analyze the candidate genes at Xq11.1-q21.33. (PMID:21384559)
• the involvement of SHP2 activity in the regulation of the expression of the fatty acid-metabolizing enzyme ACSL4 (PMID:21903867)
• The functional interaction between Acyl-CoA synthetase 4, 5-lipooxygenase and cyclooxygenase-2 controls tumor growth. (PMID:22808264)
• ACSL4 can serve as both a biomarker for, and mediator of, an aggressive breast cancer phenotype. (PMID:24155918)
• conclude that in our model system exogenous fatty acids are channeled preferentially towards phosphatidylinositol by ACSL4 overexpression (PMID:24201376)
• MiR-205 down-regulates ACSL4 through targeting its 3’UTR in hepatoma cells. (PMID:24576478)
• studies have identified a novel substrate-induced posttranslational regulatory mechanism by which AA downregulates ACSL4 protein expression in hepatic cells. (PMID:24879802)
• Upregulation of ACSL4 is responsible for the increase in triacylglycerol species containing long polyunsaturated fatty acids during activation of hepatic stellate cells. (PMID:25500141)
• Report PPARdelta-mediated regulatory mechanism for ACSL4 expression in liver tissue and cultured hepatic cells. (PMID:25645621)
• In vitro analysis showed that a recombinant COX-2 enzyme more effectively metabolized 5(S)-HETE to 5-11-diHETE compared to COX-1 enzyme. (PMID:26282205)
• we demonstrate that ACSL4 can be considered a novel activator of the mTOR pathway (PMID:26536660)
• Suggest role for ACSL4 expression in development of castration-resistant prostate cancer. (PMID:26636648)
• ACSL4 plays a tumor-suppressive role in gastric cancer. (PMID:26949059)
• ACSL4 is not only a sensitive monitor of ferroptosis, but also an important contributor of ferroptosis. (PMID:27565726)
• Data show that ELOVL7, SOCS3, ACSL4 and CLU were upregulated while PRKAR1A and ABCG1 were downregulated in the phlegm-dampness group. (PMID:27928700)
• ACLS4 and ACLS3 have roles in insulin secretion (PMID:28193492)
• Silencing of ACSL4 eliminated the 17beta-estradiol-induced increase in AA and EPA uptake. (PMID:28334272)
• These results suggest that ACSL1, ACSL4 and ACSL5 expression is regulated by ER signaling pathways and ACSL5 is a potential novel biomarker for predicting prognosis of breast cancer patients. (PMID:28498416)
• Study demonstrated that ACSL4 was overexpressed in HCC. (PMID:28887439)
• ACSL3 distribution closely overlapped with proteins involved in trafficking from the trans-Golgi network and endosomes. In contrast, the ACSL4 localisation pattern more closely followed that of calnexin which is an endoplasmic reticulum resident chaperone. (PMID:29450800)
• The regulatory network among peroxisomal ABCD2:ACSL4:VLCFA serves as a novel regulator of cartilage homeostasis, and these data may provide novel insights into the role of peroxisomal fatty acid metabolism in pathogenesis of human osteoarthritis (OA). (PMID:30264402)
• ACSL4 role in the drug resistance in breast cancer cell lines. (PMID:30414939)
• the A20-ACSL4 axis plays important roles in erastin-induced endothelial ferroptosis. (PMID:31160087)
• Regulatory mechanisms leading to differential Acyl-CoA synthetase 4 expression in breast cancer cells. (PMID:31311992)
• LncRNA NEAT1 promotes docetaxel resistance in prostate cancer by regulating ACSL4 via sponging miR-34a-5p and miR-204-5p. (PMID:31672604)
• Study shows that the expression of ACSL4 is downregulated in human glioma tissues and cells and demonstrates that ACSL4 protects glioma cells and exerts antiproliferative effects by activating a ferroptosis pathway. These results also highlight the pivotal role of ferroptosis regulation by ACSL4 in its protective effects on glioma. (PMID:31789401)

Cross-species orthologs

28 orthologs

Organism	Symbol	Gene ID
danio_rerio	acsl4a	ENSDARG00000004078
danio_rerio	acsl4b	ENSDARG00000010752
mus_musculus	Acsl4	ENSMUSG00000031278
rattus_norvegicus	Acsl4	ENSRNOG00000019180
drosophila_melanogaster	bgm	FBGN0027348
drosophila_melanogaster	pdgy	FBGN0027601
drosophila_melanogaster	CG8834	FBGN0033733
drosophila_melanogaster	CG17999	FBGN0034552
drosophila_melanogaster	CG9993	FBGN0034553
drosophila_melanogaster	Fatp3	FBGN0034999
drosophila_melanogaster	CG4563	FBGN0035006
drosophila_melanogaster	CG5568	FBGN0035641
drosophila_melanogaster	CG18586	FBGN0035642
drosophila_melanogaster	CG4830	FBGN0037996
drosophila_melanogaster	Acsx1L	FBGN0038730
drosophila_melanogaster	Acsx1R	FBGN0038731
drosophila_melanogaster	Acsx2	FBGN0038732
drosophila_melanogaster	Acsx3	FBGN0038733
drosophila_melanogaster	Acsx4	FBGN0038734
drosophila_melanogaster	Fatp2	FBGN0265187
drosophila_melanogaster	Fatp1	FBGN0267828
drosophila_melanogaster	hll	FBGN0286723
caenorhabditis_elegans		WBGENE00007082
caenorhabditis_elegans		WBGENE00008669
caenorhabditis_elegans		WBGENE00009218
caenorhabditis_elegans		WBGENE00011173
caenorhabditis_elegans		WBGENE00019920
caenorhabditis_elegans		WBGENE00022849

Paralogs (12): SLC27A5 (ENSG00000083807), ACSBG1 (ENSG00000103740), SLC27A6 (ENSG00000113396), ACSL3 (ENSG00000123983), SLC27A1 (ENSG00000130304), ACSBG2 (ENSG00000130377), SLC27A2 (ENSG00000140284), SLC27A3 (ENSG00000143554), ACSL1 (ENSG00000151726), ACSL6 (ENSG00000164398), SLC27A4 (ENSG00000167114), ACSL5 (ENSG00000197142)

Protein

Protein identifiers

Long-chain-fatty-acid–CoA ligase 4 — O60488 (reviewed: O60488)

Alternative names: Arachidonate–CoA ligase, Long-chain acyl-CoA synthetase 4

All UniProt accessions (5): O60488, A0A804HI36, D6RDA8, D6RF95, H0Y9A0

UniProt curated annotations — full annotation on UniProt →

Function. 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. Preferentially activates arachidonate and eicosapentaenoate as substrates. Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs. Modulates prostaglandin E2 secretion. 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.

Subcellular location. Mitochondrion outer membrane. Endoplasmic reticulum membrane. Cell membrane.

Post-translational modifications. Phosphorylation at Thr-328 by isoform Beta-II of PRKCB promotes activation and lipid peroxidation, thereby inducing ferroptosis. Phosphorylation at Thr-679 by PCK2 promotes ferroptosis.

Disease relevance. Intellectual developmental disorder, X-linked 63 (XLID63) [MIM:300387] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked intellectual disability, while syndromic forms presents with associated physical, neurological and/or psychiatric manifestations. The disease is caused by variants affecting the gene represented in this entry. AMME complex (ATS-MR) [MIM:300194] An X-linked contiguous gene deletion syndrome characterized by glomerulonephritis, sensorineural hearing loss, intellectual disability, midface hypoplasia and elliptocytosis. The gene represented in this entry may be involved in disease pathogenesis.

Activity regulation. Both triacsin C and rosiglitazone inhibit arachidonoyl-CoA ligase activity. Specifically inhibited by thiazolidinediones, preventing ferroptosis.

Similarity. Belongs to the ATP-dependent AMP-binding enzyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60488-1	Long, V2	yes
O60488-2	Short, V1

RefSeq proteins (4): NP_001305438, NP_001305439, NP_004449, NP_075266 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000873	AMP-dep_synth/lig_dom	Domain
IPR020845	AMP-binding_CS	Conserved_site
IPR042099	ANL_N_sf	Homologous_superfamily
IPR045851	AMP-b_sf	Homologous_superfamily

Pfam: PF00501

Enzyme classification (BRENDA):

• EC 6.2.1.15 — arachidonate-CoA ligase (BRENDA: 5 organisms, 10 substrates, 16 inhibitors, 20 Km, 0 kcat entries)
• EC 6.2.1.3 — long-chain-fatty-acid-CoA ligase (BRENDA: 48 organisms, 205 substrates, 100 inhibitors, 159 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

52 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.025–12.21	28
COA	0.0005–4.7	21
PALMITATE	0.0002–6	19
OLEATE	0.0014–3	9
ARACHIDONATE	0.0058–0.0793	7
ATP	0.029–2.39	6
COA	0.005–0.15	6
ARACHIDONATE	0.0065–9.7	6
STEARATE	0.0002–0.12	6
DECANOATE	0.004–0.0083	4
LAURATE	0.0005–0.002	4
LINOLEATE	0.0022–0.041	4
MYRISTATE	0.0002–0.0024	4
OCTANOATE	0.0007–0.0408	4
LAURIC ACID	0.0017–0.0163	3

Catalyzed reactions (Rhea), 12 shown:

• a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate (RHEA:15421)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate (RHEA:19713)
• hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate (RHEA:30751)
• (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate (RHEA:36139)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate (RHEA:44932)
• 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate (RHEA:52008)
• 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate (RHEA:52012)
• 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate (RHEA:52016)
• 5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate (RHEA:52088)
• 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate (RHEA:52108)
• 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate (RHEA:52112)
• 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate (RHEA:52116)

UniProt features (13 total): modified residue 3, sequence variant 3, mutagenesis site 2, chain 1, transmembrane region 1, sequence conflict 1, topological domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60488-F1	90.46	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 328, 447, 679

Mutagenesis-validated functional residues (2):

Position	Phenotype
328	abolished phosphorylation by isoform beta-ii of prkcb, preventing ferroptosis.
679	abolished phosphorylation by pck2, preventing ferroptosis.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-434313	Intracellular metabolism of fatty acids regulates insulin secretion
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-400451	Free fatty acids regulate insulin secretion
R-HSA-422356	Regulation of insulin secretion
R-HSA-556833	Metabolism of lipids
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 527 (showing top): AHRARNT_01, GGGACCA_MIR133A_MIR133B, RNGTGGGC_UNKNOWN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_ICOSANOID_SECRETION, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PROSTAGLANDIN_SECRETION, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, RORA1_01, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_INSULIN_SECRETION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (16): long-chain fatty acid metabolic process (GO:0001676), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), unsaturated fatty acid biosynthetic process (GO:0006636), lipid biosynthetic process (GO:0008610), neuron differentiation (GO:0030182), positive regulation of cell growth (GO:0030307), positive regulation of insulin secretion (GO:0032024), negative regulation of prostaglandin secretion (GO:0032307), long-chain fatty-acyl-CoA metabolic process (GO:0035336), long-chain fatty-acyl-CoA biosynthetic process (GO:0035338), alpha-linolenic acid metabolic process (GO:0036109), long-chain fatty acid biosynthetic process (GO:0042759), embryonic process involved in female pregnancy (GO:0060136), positive regulation of ferroptosis (GO:0160020), fatty acid derivative biosynthetic process (GO:1901570)

GO Molecular Function (7): long-chain fatty acid-CoA ligase activity (GO:0004467), ATP binding (GO:0005524), very long-chain fatty acid-CoA ligase activity (GO:0031957), arachidonate-CoA ligase activity (GO:0047676), palmitoyl-CoA ligase activity (GO:0090433), nucleotide binding (GO:0000166), ligase activity (GO:0016874)

GO Cellular Component (12): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), peroxisomal membrane (GO:0005778), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), plasma membrane (GO:0005886), membrane (GO:0016020), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), extracellular exosome (GO:0070062), peroxisome (GO:0005777)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Metabolism	2
Free fatty acids regulate insulin secretion	1
Fatty acyl-CoA biosynthesis	1
Regulation of insulin secretion	1
Integration of energy metabolism	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
long-chain fatty acid metabolic process	3
lipid metabolic process	2
fatty acid biosynthetic process	2
unsaturated fatty acid metabolic process	2
fatty acid-CoA ligase activity	2
long-chain fatty acid-CoA ligase activity	2
cellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
fatty acid metabolic process	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
biosynthetic process	1
cell differentiation	1
generation of neurons	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
negative regulation of icosanoid secretion	1
regulation of prostaglandin secretion	1
prostaglandin secretion	1
negative regulation of secretion by cell	1
fatty-acyl-CoA metabolic process	1
long-chain fatty-acyl-CoA metabolic process	1
fatty-acyl-CoA biosynthetic process	1
olefinic compound metabolic process	1
female pregnancy	1
embryo development	1
embryo development ending in birth or egg hatching	1
multicellular organismal reproductive process	1
positive regulation of programmed cell death	1
ferroptosis	1
regulation of ferroptosis	1
lipid biosynthetic process	1
fatty acid derivative metabolic process	1

Protein interactions and networks

STRING

2624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSL4	AMMECR1	Q9Y4X0	929
ACSL4	CPT1A	P50416	873
ACSL4	GPX4	P36969	834
ACSL4	SLC27A2	O14975	828
ACSL4	LPCAT3	Q6P1A2	823
ACSL4	DGAT1	O75907	819
ACSL4	COL4A5	P29400	806
ACSL4	AASDH	Q4L235	785
ACSL4	KCNE5	Q9UJ90	782
ACSL4	ASCL4	Q6XD76	722
ACSL4	COASY	Q13057	715
ACSL4	AIFM2	Q9BRQ8	700
ACSL4	FASN	P49327	694
ACSL4	SLC7A11	Q9UPY5	676
ACSL4	ABCD1	P33897	675

IntAct

144 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ACSL4	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ACSL4	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
ACSL4	DSE	psi-mi:“MI:0915”(physical association)	0.370
ACSL4	ACSL3	psi-mi:“MI:0914”(association)	0.350
FOXA3	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXL2	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXQ1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXI2	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXJ1	ACSL4	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350

BioGRID (272): ACSL4 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS), ACSL4 (Co-fractionation), ACSL3 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS), BRF1 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), ABCG1 (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), MRPS15 (Affinity Capture-MS), TJAP1 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS)

ESM2 similar proteins: A1L1K7, A7DZP8, B2KWI3, F4HUK6, I3PB36, M4IRL4, M4IS88, M4IS92, M4ISH1, M4ISH2, O22898, O35547, O60488, O80658, O95573, P30624, P35571, P39002, P39518, P47912, Q0P4F7, Q2KHW5, Q2XU92, Q4R4P9, Q4WR83, Q5FVE4, Q5R668, Q5ZKR7, Q63151, Q7ZYC4, Q8VCW8, Q8W471, Q924N5, Q96GR2, Q99PU5, Q9C7W4, Q9C8D4, Q9C9G2, Q9CAP8, Q9CZW4

Diamond homologs: A0A017SQ41, A0A0C1E6T8, A0A1B2CTC5, A0A1E3B0T2, A0A1L9NGU5, A0A1M3T4K3, A0A2I1D2N0, A0A2I2F262, A0A317VEE1, A0A318Z3U0, A0A319BQC1, A0A348AXX4, A0A395I3F8, A0A5K6CNB8, A0A823A819, A8M6W3, A8NS27, A8NVB7, B0CN26, B0XWK8, B6HLU1, B8NY88, C0LTL9, D4AU31, D9XF47, D9XF49, E9F8M3, G3XNF4, G7XQ31, M1WCQ3, O30408, O30409, O31782, O31827, O35547, O60488, O68006, O68007, O68008, O80658

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ACSL4	up-regulates	Ferroptosis
miR-3173-5p	“down-regulates quantity by repression”	ACSL4	“translation regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metal ion SLC transporters	5	30.7×	7e-05
R-HSA-425366	8	14.8×	3e-05
NCAM signaling for neurite out-growth	5	13.9×	1e-03
SLC-mediated transmembrane transport	10	6.0×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	26.2×	4e-04
neurotransmitter transport	6	18.9×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

367 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	10
Uncertain significance	135
Likely benign	29
Benign	13

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11564	NM_001318510.2(ACSL4):c.1585C>A (p.Arg529Ser)	Pathogenic
11565	NM_001318510.2(ACSL4):c.1003-2A>G	Pathogenic
1180512	GRCh37/hg19 Xq22.3-23(chrX:108168780-109606201)x0	Pathogenic
146790	GRCh38/hg38 Xq22.1-23(chrX:100597687-111651116)x4	Pathogenic
1526838	GRCh37/hg19 Xq22.2-23(chrX:103158718-111556067)	Pathogenic
1675197	NM_001318510.2(ACSL4):c.802del (p.Leu268fs)	Pathogenic
1808673	GRCh37/hg19 Xq21.33-24(chrX:93805850-118913329)x1	Pathogenic
1809431	GRCh37/hg19 Xq23(chrX:108922296-111549785)x1	Pathogenic
221776	GRCh37/hg19 Xq22.1-24(chrX:99931059-120328627)x1	Pathogenic
2684996	GRCh37/hg19 Xq21.1-24(chrX:77212972-118576590)x3	Pathogenic
2685715	GRCh37/hg19 Xq21.31-25(chrX:91274467-126799984)x1	Pathogenic
281523	NM_001318510.2(ACSL4):c.845_846del (p.His282fs)	Pathogenic
3342837	NM_001318510.2(ACSL4):c.727C>T (p.Arg243Ter)	Pathogenic
3382992	NM_001318510.2(ACSL4):c.1235dup (p.Met413fs)	Pathogenic
3391957	GRCh37/hg19 Xq21.31-23(chrX:91004293-111532472)x1	Pathogenic
394085	GRCh37/hg19 Xq22.3-23(chrX:107370001-110989043)x1	Pathogenic
394846	GRCh37/hg19 Xq21.33-26.1(chrX:95498487-129063677)x3	Pathogenic
4076021	GRCh37/hg19 Xq21.33-24(chrX:94003368-117218485)x1	Pathogenic
441843	GRCh37/hg19 Xq13.3-24(chrX:74560735-116609286)	Pathogenic
443106	GRCh37/hg19 Xq21.31-23(chrX:86776682-114054291)x1	Pathogenic
548953	GRCh37/hg19 Xq23(chrX:108919564-108929311)	Pathogenic
58661	GRCh38/hg38 Xq21.1-25(chrX:81261589-126519353)x3	Pathogenic
58667	GRCh38/hg38 Xq23(chrX:109690866-110088881)x2	Pathogenic
979829	GRCh37/hg19 Xq21.1-25(chrX:77514079-127770854)x1	Pathogenic
11566	NM_001318510.2(ACSL4):c.1001C>T (p.Pro334Leu)	Likely pathogenic
1328107	GRCh37/hg19 Xq22.3-23(chrX:104782507-112949573)x2	Likely pathogenic
1691846	NM_001318510.2(ACSL4):c.1653_1654insT (p.Lys552Ter)	Likely pathogenic
1709879	NM_001318510.2(ACSL4):c.1072_1073del (p.Leu358fs)	Likely pathogenic
1710150	NM_001318510.2(ACSL4):c.257del (p.Asn86fs)	Likely pathogenic
3362695	NM_001318510.2(ACSL4):c.1315+1G>A	Likely pathogenic

SpliceAI

2211 predictions. Top by Δscore:

Variant	Effect	Δscore
X:109659348:A:AC	donor_gain	1.0000
X:109659349:C:CC	donor_gain	1.0000
X:109659349:CTTA:C	donor_gain	1.0000
X:109659352:A:AC	donor_gain	1.0000
X:109659352:AC:A	donor_loss	1.0000
X:109659352:ACTGG:A	donor_gain	1.0000
X:109659353:C:CA	donor_gain	1.0000
X:109659353:CT:C	donor_gain	1.0000
X:109659353:CTG:C	donor_gain	1.0000
X:109659353:CTGG:C	donor_gain	1.0000
X:109659353:CTGGC:C	donor_gain	1.0000
X:109659507:GATCA:G	acceptor_gain	1.0000
X:109659509:TCA:T	acceptor_gain	1.0000
X:109659510:CA:C	acceptor_gain	1.0000
X:109659510:CAC:C	acceptor_gain	1.0000
X:109659512:C:CC	acceptor_gain	1.0000
X:109659521:C:CT	acceptor_gain	1.0000
X:109659522:A:T	acceptor_gain	1.0000
X:109661527:TTACC:T	donor_loss	1.0000
X:109661529:A:AT	donor_loss	1.0000
X:109661530:C:A	donor_loss	1.0000
X:109661642:CGAT:C	acceptor_gain	1.0000
X:109661643:GATC:G	acceptor_loss	1.0000
X:109661647:T:G	acceptor_loss	1.0000
X:109663205:TCTGA:T	donor_loss	1.0000
X:109663206:CTGAC:C	donor_loss	1.0000
X:109663207:TGAC:T	donor_loss	1.0000
X:109663210:CC:C	donor_loss	1.0000
X:109663213:ATAAT:A	donor_gain	1.0000
X:109663227:T:TA	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000045784 (X:109675740 T>C), RS1000108129 (X:109664063 T>C), RS1000118090 (X:109671841 G>A), RS1000141308 (X:109703314 C>G), RS1000142335 (X:109710205 T>C), RS1000172317 (X:109671525 G>A,C), RS1000195179 (X:109709771 G>A), RS1000333740 (X:109681531 T>C), RS1000393082 (X:109641754 C>A,G,T), RS1000437938 (X:109682548 C>T), RS1000466811 (X:109642315 T>C), RS1000583254 (X:109713218 G>A), RS1000660457 (X:109684096 T>C), RS1000723429 (X:109644532 C>A), RS1000774772 (X:109684423 G>A)

Disease associations

OMIM: gene MIM:300157 | disease phenotypes: MIM:300387, MIM:309530

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 63	Strong	X-linked
non-syndromic X-linked intellectual disability	Moderate	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
non-syndromic X-linked intellectual disability	Definitive	XL

Mondo (6): intellectual disability, X-linked 63 (MONDO:0010313), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), primary ovarian failure (MONDO:0005387), non-syndromic X-linked intellectual disability (MONDO:0019181), ischemic stroke (MONDO:1060198)

Orphanet (4): X-linked non-syndromic intellectual disability (Orphanet:777), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000365	Hearing impairment
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000545	Myopia
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000944	Abnormal metaphysis morphology
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001347	Hyperreflexia
HP:0001423	X-linked dominant inheritance
HP:0001595	Abnormal hair morphology
HP:0001643	Patent ductus arteriosus
HP:0001646	Abnormal aortic valve morphology
HP:0002907	Microscopic hematuria
HP:0004445	Elliptocytosis
HP:0005280	Depressed nasal bridge
HP:0010864	Severe intellectual disability
HP:0011069	Supernumerary tooth
HP:0011463	Childhood onset
HP:0012471	Thick vermilion border
HP:0100820	Glomerulopathy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002395_644	Mean platelet volume	2.000000e-10

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C564522	Mental Retardation, X-Linked 63 (supp.)
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680022 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

119 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ferrostatin-1	decreases reaction, increases abundance, decreases expression, affects reaction, increases expression	7
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
Valproic Acid	decreases expression, increases expression, decreases methylation, increases methylation, affects reaction	5
sodium arsenite	increases abundance, affects reaction, decreases expression, increases expression, decreases reaction (+1 more)	4
bisphenol A	decreases expression, increases expression, affects expression	3
deoxynivalenol	decreases expression, increases expression	3
methylmercuric chloride	decreases expression	2
trichostatin A	affects cotreatment, increases expression	2
cobaltous chloride	affects cotreatment, increases expression, decreases expression	2
Resveratrol	increases expression, affects cotreatment	2
Caffeine	affects phosphorylation, decreases expression	2
Chloroquine	decreases reaction, increases abundance, increases expression	2
Deferoxamine	increases expression, decreases reaction	2
Nickel	increases expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
Oleic Acid	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
aurantio-obtusin	increases expression	1
bisphenol F	increases expression	1
beauvericin	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	decreases reaction, increases expression	1
lead acetate	decreases expression	1
nuciferine	decreases reaction, increases expression	1
leonurine	decreases reaction, increases expression	1
arsenite	affects binding, decreases reaction	1
Firemaster BP-6	decreases reaction, increases expression, affects reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
beryllium sulfate	increases expression, decreases reaction, affects reaction, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4678695	Binding	Inhibition of recombinant human ACSL4 assessed as reduction in acetyl-coA prodution incubated for 120 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	Discovery of a benzimidazole series as the first highly potent and selective ACSL1 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5JF	HAP1 ACSL4 (-) 2	Cancer cell line	Male
CVCL_D7FT	Abcam A-431 ACSL4 KO	Cancer cell line	Female
CVCL_DX21	HAP1 ACSL3 (-) ACSL4 (-)	Cancer cell line	Male
CVCL_E0X3	Ubigene L-02 ACSL4 KO	Cancer cell line	Female
CVCL_F1LR	HyCyte A-549 KO-hACSL4	Cancer cell line	Male
CVCL_F1TU	HyCyte THP-1 KO-hACSL4	Cancer cell line	Male
CVCL_XK99	HAP1 ACSL4 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
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