ACSL3

Summary

ACSL3 (acyl-CoA synthetase long chain family member 3, HGNC:3570) is a protein-coding gene on chromosome 2q36.1, encoding Fatty acid CoA ligase Acsl3 (O95573). Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. It is a selective cancer dependency (DepMap: 30.5% of cell lines).

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 is highly expressed in brain, and preferentially utilizes myristate, arachidonate, and eicosapentaenoate as substrates. The amino acid sequence of this isozyme is 92% identical to that of rat homolog. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 2181 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 97 total — 5 pathogenic
• GTEx eGene: eQTL in 20 tissues, sQTL in 48 (q < 0.05)
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 30.5% of screened cell lines
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.60 (unconstrained)
• MANE Select transcript: NM_004457
• Interaction hub: 2,112 STRING partners (top 6% of genes corpus-wide)
• Notable: 97 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3570
Approved symbol	ACSL3
Name	acyl-CoA synthetase long chain family member 3
Location	2q36.1
Locus type	gene with protein product
Status	Approved
Aliases	ACS3, PRO2194
Ensembl gene	ENSG00000123983
Ensembl biotype	protein_coding
OMIM	602371
Entrez	2181

Gene structure

Transcript identifiers

Ensembl transcripts: 65 — 38 protein_coding, 14 nonsense_mediated_decay, 10 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000357430

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 6, TSL 4: 1, TSL 5: 1

ENST00000357430, ENST00000392066, ENST00000407441, ENST00000413316, ENST00000421680, ENST00000463813, ENST00000474422, ENST00000495541, ENST00000535678, ENST00000540115, ENST00000542810, ENST00000679514, ENST00000679541, ENST00000679545, ENST00000679546, ENST00000679558, ENST00000679932, ENST00000680100, ENST00000680147, ENST00000680251, ENST00000680382, ENST00000680395, ENST00000680420, ENST00000680424, ENST00000680475, ENST00000680525, ENST00000680684, ENST00000680736, ENST00000680921, ENST00000681009, ENST00000681017, ENST00000681292, ENST00000681326, ENST00000681383, ENST00000681697, ENST00000681906, ENST00000903381, ENST00000903382, ENST00000903383, ENST00000903384, ENST00000903385, ENST00000903386, ENST00000938744, ENST00000938745, ENST00000955376, ENST00000955377, ENST00000955378, ENST00000955379, ENST00000955380, ENST00000955381, ENST00000955382, ENST00001012919, ENST00001012920, ENST00001012921, ENST00001012922, ENST00001012923, ENST00001012925, ENST00001077399, ENST00001109488, ENST00001119502, ENST00001119503, ENST00001119504, ENST00001127753, ENST00001127754, ENST00001144534

RefSeq mRNA: 4 — MANE Select: NM_004457 NM_001354158, NM_001354159, NM_004457, NM_203372

CCDS: CCDS2455

Canonical transcript exons

ENST00000357430 — 17 exons

Exon	Start	End
ENSE00000786329	222919064	222919202
ENSE00000786330	222921280	222921430
ENSE00000786331	222922708	222922831
ENSE00000786332	222923078	222923149
ENSE00000786334	222927017	222927189
ENSE00000786335	222928862	222928936
ENSE00000922398	222908733	222909150
ENSE00000922400	222918046	222918155
ENSE00000922405	222924456	222924595
ENSE00000922408	222930621	222930812
ENSE00001405381	222900674	222900780
ENSE00001407067	222887830	222887888
ENSE00001733043	222933166	222933280
ENSE00001902664	222861036	222861258
ENSE00003463885	222916319	222916496
ENSE00003467287	222934530	222934687
ENSE00004805151	222941497	222944639

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 127.4037 / max 642.5973, expressed in 1826 samples.

Highest expression (Bgee): endothelial cell, lateral nuclear group of thalamus, Brodmann (1909) area 23, Brodmann (1909) area 10, Brodmann (1909) area 46.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACSL3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 48 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 68 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	5.9e-128	-1.26	2:222900773:C:T
Muscle Skeletal	sqtl	8.2e-67	-0.99	2:222912809:C:T
Artery Tibial	sqtl	4.8e-65	-1.02	2:222900773:C:T
Skin Sun Exposed Lower leg	sqtl	1.5e-55	+0.97	2:222901561:A:G
Esophagus Mucosa	sqtl	7.9e-51	+0.92	2:222912809:C:T
Adipose Subcutaneous	sqtl	2.9e-50	+0.86	2:222901409:A:G
Adipose Visceral Omentum	sqtl	1.3e-46	-0.98	2:222900773:C:T
Thyroid	sqtl	1.8e-43	+0.85	2:222942539:G:A
Stomach	sqtl	6.0e-43	+1.13	2:222900773:C:T
Cells EBV-transformed lymphocytes	sqtl	1.1e-42	-1.17	2:222912809:C:T
Lung	sqtl	1.9e-42	-0.92	2:222913955:A:G
Colon Transverse	sqtl	7.3e-42	+0.98	2:222892243:A:G
Testis	sqtl	1.5e-40	-1.09	2:222913955:A:G
Skin Not Sun Exposed Suprapubic	sqtl	7.6e-38	+0.85	2:222900773:C:T
Artery Aorta	sqtl	4.0e-36	-1.05	2:222933423:A:C
Breast Mammary Tissue	sqtl	4.2e-36	-0.88	2:222901409:A:G
Nerve Tibial	sqtl	2.7e-28	-0.81	2:222900773:C:T
Minor Salivary Gland	sqtl	2.9e-27	+1.26	2:222900231:GAAT:G
Esophagus Muscularis	sqtl	3.9e-25	-0.77	2:222940922:A:G
Colon Sigmoid	sqtl	9.8e-23	-0.84	2:222941256:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
25632	120.1498	1825
25633	4.9567	1621
25631	1.2522	832
25638	0.4970	219
25636	0.2916	113
25634	0.2563	117

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.62	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.57	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.16	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.95	gold quality
cartilage tissue	UBERON:0002418	97.61	gold quality
frontal pole	UBERON:0002795	97.59	gold quality
postcentral gyrus	UBERON:0002581	97.43	gold quality
parietal lobe	UBERON:0001872	97.41	gold quality
substantia nigra pars compacta	UBERON:0001965	97.40	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.37	gold quality
occipital lobe	UBERON:0002021	97.35	gold quality
CA1 field of hippocampus	UBERON:0003881	97.34	gold quality
entorhinal cortex	UBERON:0002728	97.28	gold quality
lateral globus pallidus	UBERON:0002476	97.23	gold quality
primary visual cortex	UBERON:0002436	97.18	gold quality
orbitofrontal cortex	UBERON:0004167	96.93	gold quality
middle frontal gyrus	UBERON:0002702	96.82	gold quality
cranial nerve II	UBERON:0000941	96.81	gold quality
adrenal tissue	UBERON:0018303	96.77	gold quality
minor salivary gland	UBERON:0001830	96.76	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.74	gold quality
middle temporal gyrus	UBERON:0002771	96.73	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.73	gold quality
superior frontal gyrus	UBERON:0002661	96.68	gold quality
superior vestibular nucleus	UBERON:0007227	96.56	gold quality
pons	UBERON:0000988	96.47	gold quality
mouth mucosa	UBERON:0003729	96.45	gold quality
prefrontal cortex	UBERON:0000451	96.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.30	gold quality
corpus callosum	UBERON:0002336	96.29	gold quality
paraflocculus	UBERON:0005351	96.23	gold quality
ventral tegmental area	UBERON:0002691	96.22	gold quality
esophagus squamous epithelium	UBERON:0006920	96.17	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.14	gold quality
colonic epithelium	UBERON:0000397	96.09	gold quality
pigmented layer of retina	UBERON:0001782	96.02	gold quality
globus pallidus	UBERON:0001875	95.96	gold quality
cardia of stomach	UBERON:0001162	95.84	gold quality
medulla oblongata	UBERON:0001896	95.82	gold quality
squamous epithelium	UBERON:0006914	95.79	gold quality
medial globus pallidus	UBERON:0002477	95.73	gold quality
cortical plate	UBERON:0005343	95.51	gold quality
esophagus mucosa	UBERON:0002469	95.50	gold quality
subthalamic nucleus	UBERON:0001906	95.38	gold quality
frontal cortex	UBERON:0001870	95.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.34	gold quality
epithelium of esophagus	UBERON:0001976	95.26	gold quality
inferior olivary complex	UBERON:0002127	95.26	gold quality
pylorus	UBERON:0001166	95.23	gold quality
cervix squamous epithelium	UBERON:0006922	95.23	gold quality
inferior vagus X ganglion	UBERON:0005363	95.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.14	gold quality
cerebral cortex	UBERON:0000956	95.08	gold quality
neocortex	UBERON:0001950	95.06	gold quality
temporal lobe	UBERON:0001871	94.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.82	gold quality
biceps brachii	UBERON:0001507	94.78	gold quality
sperm	CL:0000019	94.75	gold quality
gingival epithelium	UBERON:0001949	94.75	gold quality
telencephalon	UBERON:0001893	94.73	gold quality
corpus epididymis	UBERON:0004359	94.66	gold quality
amniotic fluid	UBERON:0000173	94.57	gold quality
stromal cell of endometrium	CL:0002255	94.54	gold quality
choroid plexus epithelium	UBERON:0003911	94.51	gold quality
saliva-secreting gland	UBERON:0001044	94.50	gold quality
calcaneal tendon	UBERON:0003701	94.44	gold quality
stomach	UBERON:0000945	94.41	gold quality
secondary oocyte	CL:0000655	94.40	gold quality
ventricular zone	UBERON:0003053	94.36	gold quality
body of stomach	UBERON:0001161	94.32	gold quality
gingiva	UBERON:0001828	94.30	gold quality
tongue squamous epithelium	UBERON:0006919	94.29	gold quality
forebrain	UBERON:0001890	94.03	gold quality
lower esophagus mucosa	UBERON:0035834	94.03	gold quality
ganglionic eminence	UBERON:0004023	93.91	gold quality
putamen	UBERON:0001874	93.87	gold quality
caudate nucleus	UBERON:0001873	93.78	gold quality
oocyte	CL:0000023	93.77	gold quality
male germ cell	CL:0000015	93.75	gold quality
Ammon’s horn	UBERON:0001954	93.75	gold quality
visceral pleura	UBERON:0002401	93.66	gold quality
tibia	UBERON:0000979	93.65	gold quality
caput epididymis	UBERON:0004358	93.64	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.63	gold quality
left testis	UBERON:0004533	93.63	gold quality
rectum	UBERON:0001052	93.59	gold quality
seminal vesicle	UBERON:0000998	93.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.53	gold quality
brain	UBERON:0000955	93.47	gold quality
cingulate cortex	UBERON:0003027	93.46	gold quality
central nervous system	UBERON:0001017	93.45	gold quality
right testis	UBERON:0004534	93.42	gold quality
bronchial epithelial cell	CL:0002328	93.41	gold quality
anterior cingulate cortex	UBERON:0009835	93.39	gold quality
hypothalamus	UBERON:0001898	93.38	gold quality
liver	UBERON:0002107	93.38	gold quality
lower lobe of lung	UBERON:0008949	93.37	gold quality
nucleus accumbens	UBERON:0001882	93.35	gold quality
right adrenal gland cortex	UBERON:0035827	93.34	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	15.53
E-GEOD-137537	yes	6.42
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Parathyroid gland	tissue	161.9	high
Caudate putamen	tissue	145.4
Frontal cortex	tissue	142.8
Spinal cord	tissue	117.6
Pons	tissue	117.4
Thalamus	tissue	114.2
Midbrain	tissue	110.7
Cerebral cortex	tissue	108.9	medium
Occipital cortex	tissue	108.9
Somatosensory cortex	tissue	108.6
Motor cortex	tissue	108.4
Medulla oblongata	tissue	106.4
Prefrontal cortex	tissue	104.9
Periaqueductal gray	tissue	103.9
Putamen	tissue	102.5
Retrosplenial and cingulate cortex	tissue	100.8
Superior colliculi	tissue	99.7
Hypothalamus	tissue	97.7
Retrosplenial cortex	tissue	96.6
Substantia nigra	tissue	96.3
Hippocampal formation	tissue	95.9
Entorhinal cortex	tissue	95.9
Septum	tissue	95.9
Ventral forebrain	tissue	93.6
Temporal cortex	tissue	92.4
Insular cortex	tissue	85.5
Breast	tissue	85.3	medium
Basal ganglia	tissue	82.6	medium
Amygdala	tissue	80.6
Olfactory bulb	tissue	79.0
Corpus callosum	tissue	74.2
Prostate	tissue	62.1	high
Cerebellum	tissue	61.2	medium
Postcentral gyrus	tissue	57.2
Locus coeruleus	tissue	54.3
Nucleus accumbens	tissue	51.3
Stomach 1	tissue	47.8	high
Hippocampus	tissue	43.8	medium
Esophagus	tissue	33.9	medium
Urinary bladder	tissue	31.3	high
Retina	tissue	29.9
Liver	tissue	28.9	high
Placenta	tissue	26.3	high
Bone marrow	tissue	26.2	high
Colon	tissue	25.4	medium
Choroid plexus	tissue	25.0
Rectum	tissue	24.0	high
Adipose tissue	tissue	23.6	medium
Epididymis	tissue	23.5	high
Kidney	tissue	22.7	high
Thyroid gland	tissue	22.3	high
Testis	tissue	21.8	high
Duodenum	tissue	20.9	high
Lung	tissue	19.5	high
Salivary gland	tissue	19.0	medium
Thymus	tissue	18.5
Vagina	tissue	18.1	low
Cervix	tissue	17.3	medium
Adrenal gland	tissue	16.9	high
Appendix	tissue	16.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (117.6), Dorsal hippocampus (93.4), Subiculum (92.5), Ventral hippocampus (89.7), Dorsal spinal cord (86.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H2, NR1H3, PPARD, RXRA

miRNA regulators (miRDB)

Targeting ACSL3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 183 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-493-5P	99.96	72.47	2382

Functional genomics

gnomAD constraint: pLI 0.0107, LOEUF 0.605, missense Z 2.51 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000357430 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:222,908,773–222,921,336	333 / 347.5	0.96	no
2:222,921,337–222,941,651	347 / 525.7	0.66	no
DepMap (CRISPR cell-line fitness): dependent in 30.5% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): CHLA-10 (-1.98), MHH-ES-1 (-1.964), SLR 20 (-1.954), G415 (-1.952), KP-3 (-1.946), SCC-4 (-1.816), PF-382 (-1.79), OV7 (-1.723), Hey-A8 (-1.716), A-375 (-1.71), OVCAR-8 (-1.695), PA-TU-8902 (-1.659), KOSC-2 (-1.656), OVCAR-5 (-1.6), SCCH-196 (-1.587).

Literature-anchored findings (GeneRIF, showing 24)

• Sequence analysis of genomic clones demonstrates that the human ACS3 gene spans at least 80.6 kb and contains 17 exons. (PMID:11707336)
• Repression of FAS mRNA expression is the consequence of feedback inhibition of FAS expression by long chain fatty acyl-CoAs, which are formed by FACL3 during its upregulation by vitamin D3in prostate cancer cells. (PMID:15556626)
• Oncostatin M directly lowers the plasma triglycerides in hyperlipidemia by stimulating the transcription of ACSL3/5 in the liver. (PMID:17761945)
• Data suggest that endogenous FATP4 does not function to translocate fatty acids across the plasma membrane, but functions more as a very long-chain acyl-CoA synthetase. (PMID:17901542)
• Small interfering RNA targeting ACSL3 inhibits secretion of hepatitis c virus from human hepatoma-derived cells (PMID:18003621)
• Data suggest that methylated ACSL3 5’CpG islands in umbilical cord white blood cell DNA may be a surrogate endpoint for transplacental polycyclic aromatic hydrocarbon exposure and/or a potential biomarker for environmentally-related asthma. (PMID:19221603)
• Results suggest that liver X receptors play a regulatory role in fatty acid metabolism by direct regulation of ACSL3 in human placental trophoblast cells. (PMID:20219900)
• ACSL3 is a novel molecular target of PPARdelta in HepG2 cells; there is a regulatory mechanism for ACSL3 transcription in liver tissue (PMID:20308079)
• Results suggest that initiation of Golgi export of Lyn involves association of ACSL3 with the Lyn C-lobe, which is exposed to the molecular surface in an open conformation. (PMID:20605918)
• expression of ACSL3 was induced by endoplasmic reticulum stress (PMID:21328461)
• role of N-terminal region of acyl-CoA synthetase 3 in its function and localization on lipid droplets (PMID:22357706)
• activation of fatty acid import is linked to the up-regulation of cellular long chain acyl-CoA synthetase activity and identify the long chain acyl-CoA syntheatse3 (Acsl3) as a novel host factor required for polio replication. (PMID:23762027)
• The prominent expression of ACSL3 in VSMC. (PMID:23840832)
• ACSL3 is essential for mutant KRAS lung cancer tumorigenesis in vivo and is highly expressed in human lung cancer (PMID:27477280)
• ACLS4 and ACLS3 have roles in insulin secretion (PMID:28193492)
• Study shows that ACSL3 contributes to intratumoral steroidogenesis by modulating the steroidogenic genes and plays an important role in the growth of castration-resistant prostate cancer. (PMID:28771887)
• 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)
• Subcellular fractionation showed that at least 68% of ACSL3 remain at the ER even during extensive fatty acid supplementation. High resolution single molecule microscopy confirmed the abundance of cytoplasmic ACSL3 outside of LDs. (PMID:29526665)
• The ACSL3-LPIAT1 signaling drives prostaglandin synthesis in non-small cell lung cancer. (PMID:32034305)
• Immunohistochemical staining reveals differential expression of ACSL3 and ACSL4 in hepatocellular carcinoma and hepatic gastrointestinal metastases. (PMID:32286604)
• Metabolic enzyme ACSL3 is a prognostic biomarker and correlates with anticancer effectiveness of statins in non-small cell lung cancer. (PMID:33030783)
• Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer. (PMID:35182729)
• [Research advances on the role of ACSL3 in the atherosclerosis]. (PMID:37583046)
• ANKRD1 aggravates renal ischaemia-reperfusion injury via promoting TRIM25-mediated ubiquitination of ACSL3. (PMID:39285846)

Cross-species orthologs

27 orthologs

Organism	Symbol	Gene ID
danio_rerio	acsl3b	ENSDARG00000014674
mus_musculus	Acsl3	ENSMUSG00000032883
rattus_norvegicus	Acsl3	ENSRNOG00000014718
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): ACSL4 (ENSG00000068366), SLC27A5 (ENSG00000083807), ACSBG1 (ENSG00000103740), SLC27A6 (ENSG00000113396), SLC27A1 (ENSG00000130304), ACSBG2 (ENSG00000130377), SLC27A2 (ENSG00000140284), SLC27A3 (ENSG00000143554), ACSL1 (ENSG00000151726), ACSL6 (ENSG00000164398), SLC27A4 (ENSG00000167114), ACSL5 (ENSG00000197142)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1921455) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body length	1
decreased body weight	1
postnatal growth retardation	1
abnormal humoral immune response	1
abnormal postnatal growth/weight/body size	1
decreased lean body mass	1
decreased B cell number	1
increased CD4-positive, alpha-beta T cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Arthrobacter sp.	P86831	100.0%	Diamond
Pongo abelii	Q5R668	99.7%	Diamond
Humulus lupulus	M4IRL4	97.9%	Diamond
Cavia porcellus	Q9JID6	88.7%	Diamond
Mycobacterium marinum M	B2HHZ8	81.0%	Diamond
Arabidopsis thaliana	Q9T009	80.4%	Diamond
Saccharomyces cerevisiae S288C	P39002	78.5%	Diamond
Rhodococcus rhodochrous	E3UUE6	67.2%	Diamond
Fusarium graminearum PH-1	I1S3K7	58.8%	Diamond
Dictyostelium discoideum	Q55DR6	45.8%	Diamond
Teredinibacter turnerae T7901	C5BK10	45.3%	Diamond
Schizosaccharomyces pombe 972h-	O60135	43.3%	Diamond
Mycosarcoma maydis	Q4PEM9	41.6%	Diamond
Fusarium verticillioides 7600	W7L9F0	41.0%	Diamond
Aspergillus fumigatus Af293	Q4WR82	39.1%	Diamond
Orbilia oligospora ATCC 24927	G1XSR7	38.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ACSL3-AS1	ncRNA	105373904
KCNE4	protein-coding	23704
MOGAT1	protein-coding	116255

Protein

Protein identifiers

Fatty acid CoA ligase Acsl3 — O95573 (reviewed: O95573)

Alternative names: Arachidonate–CoA ligase, Long-chain acyl-CoA synthetase 3, Long-chain-fatty-acid–CoA ligase 3, Medium-chain acyl-CoA ligase Acsl3

All UniProt accessions (10): A0A7P0T8L6, A0A7P0T905, A0A7P0TA76, A0A7P0TB52, A0A7P0TBB1, A0A7P0TBL9, C9JC11, F5GWH2, H7BYZ7, O95573

UniProt curated annotations — full annotation on UniProt →

Function. Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins). Has mainly an anabolic role in energy metabolism. Mediates hepatic lipogenesis. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates. Both isoforms exhibit the same level of activity.

Subcellular location. Mitochondrion outer membrane. Peroxisome membrane. Microsome membrane. Endoplasmic reticulum membrane.

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

RefSeq proteins (4): NP_001341087, NP_001341088, NP_004448, NP_976251 (=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

Pfam: PF00501

Enzyme classification (BRENDA)

• 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)

48 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	0.0065–9.7	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
LINOLENATE	0.0016–0.0073	2
OCTADECANOATE	0.061–0.072	2
PALMITOLEATE	0.0015–0.002	2

Catalyzed reactions (Rhea)

• 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)
• (9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate (RHEA:33607)
• octadecanoate + ATP + CoA = octadecanoyl-CoA + AMP + diphosphate (RHEA:33615)
• tetradecanoate + ATP + CoA = tetradecanoyl-CoA + AMP + diphosphate (RHEA:33619)
• dodecanoate + ATP + CoA = dodecanoyl-CoA + AMP + diphosphate (RHEA:33623)
• (9Z)-hexadecenoate + ATP + CoA = (9Z)-hexadecenoyl-CoA + AMP + diphosphate (RHEA:33647)
• (9Z,12Z)-octadecadienoate + ATP + CoA = (9Z,12Z)-octadecadienoyl-CoA + AMP + diphosphate (RHEA:33651)
• (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate (RHEA:36139)
• a fatty acid + ATP + CoA = a fatty acyl-CoA + AMP + diphosphate (RHEA:38883)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate (RHEA:44932)

UniProt features (6 total): chain 1, transmembrane region 1, topological domain 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95573-F1	88.79	0.63

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins, Cancer-related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; nucleoli rim; lipid droplets

Antibody reliability (HPA): IH approved · IF approved

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 (1)

Type	Positions
Phosphoserine	683

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

9 pathways:

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

MSigDB gene sets: 415 (showing top): REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, MODULE_52, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, PAX4_01, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, GCM_ZNF198, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (11): long-chain fatty acid metabolic process (GO:0001676), fatty acid metabolic process (GO:0006631), neuron differentiation (GO:0030182), very-low-density lipoprotein particle assembly (GO:0034379), long-chain fatty-acyl-CoA metabolic process (GO:0035336), long-chain fatty-acyl-CoA biosynthetic process (GO:0035338), positive regulation of Golgi to plasma membrane protein transport (GO:0042998), long-chain fatty acid import into cell (GO:0044539), positive regulation of secretion (GO:0051047), positive regulation of phosphatidylcholine biosynthetic process (GO:2001247), lipid metabolic process (GO:0006629)

GO Molecular Function (11): long-chain fatty acid-CoA ligase activity (GO:0004467), ATP binding (GO:0005524), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), medium-chain fatty acid-CoA ligase activity (GO:0031956), arachidonate-CoA ligase activity (GO:0047676), palmitoyl-CoA ligase activity (GO:0090433), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874), fatty acid-CoA ligase activity (GO:0120515)

GO Cellular Component (9): mitochondrial outer membrane (GO:0005741), peroxisomal membrane (GO:0005778), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), lipid droplet (GO:0005811), plasma membrane (GO:0005886), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

7 top-level categories:

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

51 GO namespaces:

Category	Terms
cytoplasm	3
fatty acid-CoA ligase activity	2
long-chain fatty acid-CoA ligase activity	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
fatty acid metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
cell differentiation	1
generation of neurons	1
plasma lipoprotein particle assembly	1
fatty-acyl-CoA metabolic process	1
long-chain fatty-acyl-CoA metabolic process	1
fatty-acyl-CoA biosynthetic process	1
regulation of Golgi to plasma membrane protein transport	1
Golgi to plasma membrane protein transport	1
positive regulation of protein transport	1
positive regulation of protein localization to plasma membrane	1
long-chain fatty acid transport	1
import into cell	1
lipid import into cell	1
secretion	1
regulation of secretion	1
positive regulation of transport	1
phosphatidylcholine biosynthetic process	1
positive regulation of phospholipid biosynthetic process	1
regulation of phosphatidylcholine biosynthetic process	1
primary metabolic process	1
long-chain fatty acid metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
kinase binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
fatty acid ligase activity	1
CoA-ligase activity	1
mitochondrial membrane	1
organelle outer membrane	1
peroxisome	1
microbody membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
long-chain fatty acid import into cell	BP	direct assay
long-chain fatty acid metabolic process	BP	mutant phenotype
positive regulation of Golgi to plasma membrane protein transport	BP	mutant phenotype
positive regulation of phosphatidylcholine biosynthetic process	BP	mutant phenotype
positive regulation of secretion	BP	mutant phenotype
very-low-density lipoprotein particle assembly	BP	mutant phenotype
Golgi apparatus	CC	direct assay
endoplasmic reticulum	CC	direct assay
lipid droplet	CC	direct assay
membrane	CC	high-throughput assay
perinuclear region of cytoplasm	CC	direct assay
long-chain fatty acid-CoA ligase activity	MF	mutant phenotype
protein domain specific binding	MF	physical interaction
protein kinase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,112 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSL3	AASDH	Q4L235	890
ACSL3	DGAT1	O75907	854
ACSL3	ABCD1	P33897	736
ACSL3	SLC27A2	O14975	688
ACSL3	CD36	P16671	668
ACSL3	ABCD3	P28288	667
ACSL3	HADHB	P55084	664
ACSL3	CPT2	P23786	645
ACSL3	SCARB2	Q14108	636
ACSL3	SCARB1	Q8WTV0	631
ACSL3	FASN	P49327	626
ACSL3	ACADL	P28330	624
ACSL3	LPCAT3	Q6P1A2	624
ACSL3	SCD	O00767	619
ACSL3	ACACA	Q13085	595

IntAct

Human interaction partners of ACSL3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
IFT140	association	0.510	2
STX17	physical association	0.470	5
C15orf40	physical association	0.400	1
DDX42	physical association	0.400	1
DOCK11	physical association	0.400	1
NDRG1	physical association	0.400	1
TTBK1	physical association	0.400	1
ACSL4	association	0.350	1
ARMC5	association	0.350	1
ATP2B1	association	0.350	1
KIF20B	association	0.350	1
GTF2F2	physical association	0.000	1
WDR19	physical association	0.000	1

BioGRID (371 interactions; top human partners by supporting records): ACSL4 (Affinity Capture-MS; 5 records), GNAT2 (Affinity Capture-MS; 3 records), LYN (Affinity Capture-MS; 3 records), CANX (Proximity Label-MS; 2 records), CCNF (Affinity Capture-MS; 2 records), CDC42 (Affinity Capture-MS; 2 records), ESYT1 (Proximity Label-MS; 2 records), HERPUD1 (Affinity Capture-MS; 2 records), LAMP1 (Proximity Label-MS; 2 records), NDRG1 (Proximity Label-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), RAB5A (Affinity Capture-MS; 2 records), REEP5 (Affinity Capture-MS; 2 records), RICTOR (Proximity Label-MS; 2 records), RPN2 (Proximity Label-MS; 2 records)

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — AML.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for ACSL3: 97 ClinVar records (5 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	62
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
635897	Single allele	Pathogenic	criteria provided, single submitter	1
1526954	GRCh37/hg19 2q36.1(chr2:222828685-224451613)x1	Pathogenic	criteria provided, single submitter	1
1526955	GRCh37/hg19 2q36.1-37.1(chr2:223378640-232061074)x1	Pathogenic	criteria provided, single submitter	1
3148939	GRCh37/hg19 2q35-37.3(chr2:216815496-242782258)x3	Pathogenic	criteria provided, single submitter	1
146029	GRCh38/hg38 2q36.1-36.2(chr2:221663502-224426183)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ACSL3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,632):

Position(s)	Effect	Δscore	Sites
2:222861259–222861260	donor_loss	1.0000	4
2:222916317–222916318	acceptor_loss	1.0000	4
2:222918156–222918157	donor_loss	1.0000	5
2:222919057	acceptor_gain	1.0000
2:222919062–222919063	acceptor_loss	1.0000	6
2:222919203–222919204	donor_loss	1.0000	5
2:222921278–222921279	acceptor_loss	1.0000	3
2:222921431–222921432	donor_loss	1.0000	5
2:222922832–222922833	donor_loss	1.0000	2
2:222924447–222924451	acceptor_gain	1.0000	3

AlphaMissense

1,823 missense substitutions predicted likely pathogenic (of 4,718 scored), across 468 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M285	9	0.875	0.982
D564	8	0.998	1.000
D371	8	0.994	0.998
D578	8	0.992	0.999
H332	8	0.988	0.997
D582	8	0.985	0.996
F434	8	0.976	0.996
F409	8	0.968	0.996
F462	8	0.966	0.998
S288	8	0.965	0.998
D388	8	0.958	0.996
D491	8	0.948	0.989
D322	8	0.947	0.982
F124	8	0.911	0.984
F467	8	0.763	0.956
W687	7	0.995	1.000
W511	7	0.992	0.999
E598	7	0.990	0.997
E479	7	0.984	0.993
W559	7	0.982	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.11e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.09e-05
Lung Adenocarcinoma (TCGA)	unfavorable	0.00045
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000971

Disease associations

OMIM: gene MIM:602371 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

GWAS associations

1 associations:

Study	Trait	p-value
GCST003124_27	Mild influenza (H1N1) infection	2e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680023 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

3 measured of 5 human assays (6 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM
CHEMBL4761388	IC50	69000 nM
CHEMBL4776019	IC50	114000 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 5 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.24	Kd	5733	nM	CHEMBL3752910
5.24	ED50	5733	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 14 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147790: Binding affinity to human ACSL3 incubated for 45 mins by Kinobead based pull down assay	kd	5.7331	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	6
Benzo(a)pyrene	decreases expression, decreases methylation	5
bisphenol A	affects expression, decreases methylation, increases expression	3
sodium arsenite	affects expression, decreases expression	3
Acetaminophen	affects expression, increases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance	3
Tetrachlorodibenzodioxin	affects expression, decreases expression, affects cotreatment	3
Metribolone	increases reaction, increases expression, affects binding	3
Cyclosporine	affects expression, increases expression	3
methylselenic acid	decreases expression, affects expression	2
trichostatin A	affects expression, increases expression	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Genistein	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
graphene oxide	increases expression	1
dicrotophos	decreases expression	1
daidzein	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
senecionine	decreases expression	1
daidzin	decreases expression, affects cotreatment	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
genistin	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	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
CHEMBL4678697	Binding	Inhibition of recombinant human ACSL3 assessed as reduction in acetyl-coA prodution incubated for 90 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

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1IW	Abcam HeLa ACSL3 KO	Cancer cell line	Female
CVCL_DX21	HAP1 ACSL3 (-) ACSL4 (-)	Cancer cell line	Male
CVCL_F5DE	EDITGENE ACSL3 Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_XK98	HAP1 ACSL3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00117546	Phase 4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	Phase 4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	Phase 4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	Phase 4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	Phase 4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	Phase 4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	Phase 4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	Phase 4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	Phase 4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	Phase 4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	Phase 4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	Phase 4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	Phase 4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	Phase 4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	Phase 4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	Phase 4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	Phase 4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	Phase 4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	Phase 4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	Phase 4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	Phase 4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	Phase 4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	Phase 4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	Phase 4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	Phase 4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	Phase 4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	Phase 4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	Phase 4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	Phase 4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	Phase 4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	Phase 4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	Phase 4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	Phase 4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	Phase 4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	Phase 4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	Phase 4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	Phase 4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	Phase 4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	Phase 4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	Phase 4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial
NCT06359015	Phase 4	TERMINATED	Metformin and Esomeprazole in Preterm Pre-eclampsia
NCT06468202	Phase 4	RECRUITING	Effectiveness of Two Aspirin Doses for Prevention of Hypertensive Disorders of Pregnancy: ASPIRIN TRIAL
NCT06632379	Phase 4	RECRUITING	AtorvaStatin Postpartum and Reduction of Cardiovascular risK
NCT06785116	Phase 4	RECRUITING	A Randomized, Placebo-controlled Trial of DAPAgliflozin (DAPA) for Cardiovascular Risk Reduction in the Postpartum Period of Hypertensive Pregnancies (HP)
NCT07167862	Phase 4	NOT_YET_RECRUITING	Optimizing Preeclampsia Postpartum With Point-of-care Ultrasound
NCT07288801	Phase 4	RECRUITING	Vitamin D for Preventing Recurrent Preeclampsia in Pregnant Women
NCT07293728	Phase 4	NOT_YET_RECRUITING	A Randomized Feasibility Trial Comparing Drospirenone and Norethindrone for Postpartum Hypertension Management in Preeclampsia
NCT07361679	Phase 4	RECRUITING	LDA and LMWH vs LDA Alone in High-risk Patients for Preeclampsia Prevention
NCT07448597	Phase 4	RECRUITING	Progesterone Preeclampsia
NCT07510568	Phase 4	NOT_YET_RECRUITING	Vitamin D Supplementation Among Pregnant Women in Uganda for the Prevention of Hypertensive Disorders in Pregnancy, and Other Adverse Maternal and Foetal Outcomes
NCT07717931	Phase 4	COMPLETED	Vitamin D Therapy to Prevent Recurrent Preeclampsia in High-Risk Pregnancies
NCT07779057	Phase 4	RECRUITING	Comparison of High- Versus Low-Dose Aspirin for Pregnancy Outcomes in Women at High Risk of Preeclampsia
NCT07793760	Phase 4	NOT_YET_RECRUITING	Dexamethasone Versus Ondansetron for Preventing Post-Spinal Hypotension in Preeclampsia
NCT00000534	Phase 3	COMPLETED	Calcium for Pre-Eclampsia Prevention (CPEP)
NCT00097110	Phase 3	COMPLETED	RCT of Antioxidant Therapy to Prevent Preeclampsia in Brazil
NCT00135707	Phase 3	COMPLETED	Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS)
NCT00157521	Phase 3	COMPLETED	L-Arginine in Pre-Eclampsia
NCT00197340	Phase 3	COMPLETED	Antepartum Chronic Epidural Therapy (ACET) to Improve Blood Flow to the Uterus, Placenta and Baby in Pre-Eclampsia and Intrauterine Growth Restriction
NCT00300937	Phase 3	COMPLETED	Coenzyme Q10 Supplementation and Development of Preeclampsia
NCT00848679	Phase 3	WITHDRAWN	Investigating the Novel Observation of Right-left Difference in Uterine Artery Vascular Resistance in Pre-eclampsia

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACSL3 across ~30M SureChEMBL compounds — explore on Sugi Predict.