ACSL1

Summary

ACSL1 (acyl-CoA synthetase long chain family member 1, HGNC:3569) is a protein-coding gene on chromosome 4q35.1, encoding Long-chain-fatty-acid–CoA ligase 1 (P33121). Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs 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. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2180 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 159 total — 46 pathogenic, 4 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001995

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3569
Approved symbol	ACSL1
Name	acyl-CoA synthetase long chain family member 1
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	LACS2, LACS, ACS1, LACS1, FACL1
Ensembl gene	ENSG00000151726
Ensembl biotype	protein_coding
OMIM	152425
Entrez	2180

Gene structure

Transcript identifiers

Ensembl transcripts: 96 — 94 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000281455, ENST00000454703, ENST00000503407, ENST00000504342, ENST00000504900, ENST00000505492, ENST00000506733, ENST00000507295, ENST00000513001, ENST00000513317, ENST00000515030, ENST00000706366, ENST00000706367, ENST00000706368, ENST00000706369, ENST00000706370, ENST00000864687, ENST00000864688, ENST00000864689, ENST00000864690, ENST00000864691, ENST00000864692, ENST00000864693, ENST00000864694, ENST00000864695, ENST00000864696, ENST00000864697, ENST00000864698, ENST00000864699, ENST00000864700, ENST00000864701, ENST00000864702, ENST00000864703, ENST00000864704, ENST00000864705, ENST00000864706, ENST00000864707, ENST00000864708, ENST00000864709, ENST00000864710, ENST00000864711, ENST00000864712, ENST00000864713, ENST00000864714, ENST00000864715, ENST00000864716, ENST00000864717, ENST00000864718, ENST00000864719, ENST00000864720, ENST00000864721, ENST00000864722, ENST00000864723, ENST00000864724, ENST00000864725, ENST00000864726, ENST00000864727, ENST00000864728, ENST00000864729, ENST00000864730, ENST00000864731, ENST00000864733, ENST00000864734, ENST00000864735, ENST00000864736, ENST00000864737, ENST00000864738, ENST00000864739, ENST00000864740, ENST00000864741, ENST00000864742, ENST00000864743, ENST00000864744, ENST00000864745, ENST00000864746, ENST00000950924, ENST00000950925, ENST00000950926, ENST00000950927, ENST00000950928, ENST00000950929, ENST00000950930, ENST00000950931, ENST00000950932, ENST00000950933, ENST00000950934, ENST00000950935, ENST00000950936, ENST00000950937, ENST00000950938, ENST00000950939, ENST00000950940, ENST00000950941, ENST00000950942, ENST00000950943, ENST00000950944

RefSeq mRNA: 18 — MANE Select: NM_001995 NM_001286708, NM_001286710, NM_001286711, NM_001381877, NM_001381878, NM_001381879, NM_001381880, NM_001381881, NM_001381882, NM_001381883, NM_001381884, NM_001381885, NM_001381886, NM_001381887, NM_001381888, NM_001381889, NM_001381890, NM_001995

CCDS: CCDS3839, CCDS68825, CCDS68826

Canonical transcript exons

ENST00000281455 — 21 exons

Exon	Start	End
ENSE00003474060	184788617	184788731
ENSE00003500813	184755595	184757265
ENSE00003507486	184768316	184768450
ENSE00003524468	184803320	184803546
ENSE00003529677	184780332	184780433
ENSE00003546527	184783927	184783991
ENSE00003551939	184757635	184757706
ENSE00003567695	184776884	184776983
ENSE00003578195	184764853	184764925
ENSE00003589613	184776484	184776662
ENSE00003593817	184766622	184766756
ENSE00003596055	184773081	184773154
ENSE00003606251	184765891	184765986
ENSE00003636383	184762407	184762523
ENSE00003658512	184773843	184773875
ENSE00003658572	184770399	184770476
ENSE00003681359	184773663	184773714
ENSE00003682326	184760357	184760500
ENSE00003687766	184763167	184763255
ENSE00003690209	184757819	184757920
ENSE00003995657	184825916	184825968

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.5534 / max 5935.1922, expressed in 1777 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55182	46.2508	1172
55184	18.5015	1742
55165	3.1248	310
55167	1.3292	387
55163	1.1236	118
55164	0.9271	173
55183	0.7187	229
55173	0.5283	86
55166	0.5252	161
55177	0.3030	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.52	gold quality
upper leg skin	UBERON:0004262	99.35	gold quality
liver	UBERON:0002107	99.27	gold quality
blood	UBERON:0000178	99.23	gold quality
renal medulla	UBERON:0000362	99.10	gold quality
gastrocnemius	UBERON:0001388	99.08	gold quality
adipose tissue	UBERON:0001013	98.96	gold quality
parotid gland	UBERON:0001831	98.90	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.88	gold quality
upper arm skin	UBERON:0004263	98.83	gold quality
skin of hip	UBERON:0001554	98.79	gold quality
pericardium	UBERON:0002407	98.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.77	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.75	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.71	gold quality
muscle of leg	UBERON:0001383	98.70	gold quality
omental fat pad	UBERON:0010414	98.66	gold quality
peritoneum	UBERON:0002358	98.64	gold quality
biceps brachii	UBERON:0001507	98.63	gold quality
muscle organ	UBERON:0001630	98.63	gold quality
skeletal muscle organ	UBERON:0014892	98.63	gold quality
right lung	UBERON:0002167	98.62	gold quality
skin of abdomen	UBERON:0001416	98.59	gold quality
synovial joint	UBERON:0002217	98.59	gold quality
diaphragm	UBERON:0001103	98.58	gold quality
mammalian vulva	UBERON:0000997	98.57	gold quality
skeletal muscle tissue	UBERON:0001134	98.51	gold quality
vastus lateralis	UBERON:0001379	98.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.47	gold quality
zone of skin	UBERON:0000014	98.45	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	5161.54
E-GEOD-84465	yes	2963.45
E-GEOD-180759	yes	2375.21
E-HCAD-9	yes	54.28
E-GEOD-135922	yes	51.61
E-MTAB-8142	yes	44.63
E-MTAB-9221	yes	19.63
E-MTAB-9801	yes	10.05
E-MTAB-5061	no	2647.82
E-ENAD-27	no	3.82
E-HCAD-31	no	3.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, IRF6, PPARA, PPARG, SREBF1, SREBF2, STAT1

miRNA regulators (miRDB)

131 targeting ACSL1, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4531	99.99	69.70	3181
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
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4671-3P	99.88	72.46	1045

Literature-anchored findings (GeneRIF, showing 32)

• Based on homology, two new isoforms for ACSL1 were predicted and characterized, one represented a switch of the Phe- to the Tyr-Gate domain motif, the other resulted from the exclusion of both. (PMID:16834775)
• Data show that ACSL1 rs9997745 polymorphism influences metabolic syndrome risk, most likely via disturbances in fatty acid metabolism, which was modulated by dietary fat consumption, particularly PUFA intake, suggesting novel gene-nutrient interactions. (PMID:20176858)
• Findings suggest that the ACSL1 gene polymorphism rs6552828 is not associated with elite endurance athletic status in Caucasians, yet a marginal association seems to exist for the Chinese (Han) male population. (PMID:22829935)
• INSR rs1366600, ACSL1 rs2292899 and FABP2 rs11724758 could influence the susceptibility to type 2 diabetes in Chinese Han population, most likely through their effects on the specific miRNA-binding sites. (PMID:23303383)
• long-chain acyl-CoA synthetase 1 has a role in eicosapentaenoic acid suppression of palmitate-induced cytokine production (PMID:23433401)
• Data indicate that expression of miR-205 is negatively related to that of ACSL1 in clinical hepatocellular carcinoma (HCC) tissues. (PMID:24462768)
• the cell surface protein CD36/FAT directly facilitates fatty acid transport across the plasma membrane, whereas the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping (PMID:24503477)
• ACSL1 is a programmable mediator of insulin sensitivity and cellular lipid content. (PMID:25915184)
• evidence in humans of ACSL1 SNPs associated with fasting glucose, diabetes, and subclinical atherosclerosis (PMID:26711138)
• SRE motif in ACSL1 is essential for SREBP2-mediated activation of C-ACSL1 gene transcription. (PMID:26728456)
• Study identified a genetic variant in the 3’-UTR region of ACSL1 gene (rs8086) that may play a significant role in predicting outcomes of stage II/III patients with colon cancer, so that patients with T/T genotype had a significantly higher risk of tumor recurrence than those carrying at least one C allele. (PMID:27992526)
• The mRNA levels of ACSL1 were positively associated with those of HBXIP in clinical breast cancer tissues. Thus, we conclude that the oncoprotein HBXIP is able to up-regulate ACSL1 through activating the transcriptional factor Sp1 in breast cancer. (PMID:28132807)
• 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)
• Both ACSL1 rs9997745 and PPARGC1A rs8192678 are associated with pre-diabetes mellitus in Mexican-Mestizos, and obesity/BMI significantly modified their association. (PMID:30041843)
• Inhibition of ACSL1 activity in the cells with triacsin C significantly suppressed the expression of these inflammatory markers and TNF-alpha-induced inflammatory markers expression in monocytic cells requires ACSL1. (PMID:30845379)
• ACSL1 expression was remarkably reduced in clear cell renal cell carcinoma cells. (PMID:31089396)
• Expression of ACSL1 and Nrf2 were down-regulated in obesity-related nephropathy (ORN) patients, ob/ob mice and palmitic acid-treated HK-2 cells. Nrf2 downregulation increases reactive oxygen species production and oxidative stress. Increased oxidative stress will suppress the expression of ACSL1 ultimately leading to renal lipid deposition in renal tubulars and accelerating the development of ORN. (PMID:31488013)
• ACSL1 Regulates TNFalpha-Induced GM-CSF Production by Breast Cancer MDA-MB-231 Cells. (PMID:31581558)
• We conclude that acs-13 mutations in C. elegans and ACSL1 knockdown in human cells prevent lipotoxicity by promoting increased levels of polyunsaturated fatty acid-containing phospholipids (PMID:31769755)
• ACSL1 affects Triglyceride Levels through the PPARgamma Pathway. (PMID:32218693)
• Metabolic reprogramming of ovarian cancer involves ACSL1-mediated metastasis stimulation through upregulated protein myristoylation. (PMID:33082557)
• Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation. (PMID:33564069)
• Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. (PMID:33854057)
• Circular RNA circACSL1 aggravated myocardial inflammation and myocardial injury by sponging miR-8055 and regulating MAPK14 expression. (PMID:33986259)
• Common genetic basis of ALS patients and soccer players may contribute to disease risk. (PMID:35249138)
• FATP2 regulates non-small cell lung cancer by mediating lipid metabolism through ACSL1. (PMID:37172427)
• Identification of toll-like receptor 5 and acyl-CoA synthetase long chain family member 1 as hub genes are correlated with the severe forms of COVID-19 by Weighted gene co-expression network analysis. (PMID:37823415)
• Fatty acids and inflammatory stimuli induce expression of long-chain acyl-CoA synthetase 1 to promote lipid remodeling in diabetic kidney disease. (PMID:38016515)
• RBM45 reprograms lipid metabolism promoting hepatocellular carcinoma via Rictor and ACSL1/ACSL4. (PMID:38040804)
• ACSL1: A preliminary study that provides a new target for the treatment of renal fibrosis could bring new insights in diabetic kidney disease. (PMID:38245444)
• ACSL1-Mediated Fatty Acid beta-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer. (PMID:38420815)
• The PRMT6/STAT1/ACSL1 axis promotes ferroptosis in diabetic nephropathy. (PMID:39134684)

Cross-species orthologs

28 orthologs

Organism	Symbol	Gene ID
danio_rerio	acsl1b	ENSDARG00000003854
danio_rerio	acsl1a	ENSDARG00000030514
mus_musculus	Acsl1	ENSMUSG00000018796
rattus_norvegicus	Acsl1	ENSRNOG00000010633
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), ACSL3 (ENSG00000123983), SLC27A1 (ENSG00000130304), ACSBG2 (ENSG00000130377), SLC27A2 (ENSG00000140284), SLC27A3 (ENSG00000143554), ACSL6 (ENSG00000164398), SLC27A4 (ENSG00000167114), ACSL5 (ENSG00000197142)

Protein

Protein identifiers

Long-chain-fatty-acid–CoA ligase 1 — P33121 (reviewed: P33121)

Alternative names: Acyl-CoA synthetase 1, Arachidonate–CoA ligase, Long-chain acyl-CoA synthetase 1, Long-chain acyl-CoA synthetase 2, Long-chain fatty acid-CoA ligase 2, Palmitoyl-CoA ligase 1, Palmitoyl-CoA ligase 2, Phytanate–CoA ligase

All UniProt accessions (8): P33121, A0A994J7S4, B7Z3Z9, D6RER0, D6RG07, E7EPM6, H0Y9U7, H0Y9Z9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses palmitoleate, oleate and linoleate. Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs).

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

Tissue specificity. Highly expressed in liver, heart, skeletal muscle, kidney and erythroid cells, and to a lesser extent in brain, lung, placenta and pancreas.

Activity regulation. Inhibited at high temperature and by arachidonate.

Miscellaneous. May be due to a competing acceptor splice site.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P33121-1	1	yes
P33121-2	2
P33121-3	3

RefSeq proteins (18): NP_001273637, NP_001273639, NP_001273640, NP_001368806, NP_001368807, NP_001368808, NP_001368809, NP_001368810, NP_001368811, NP_001368812, NP_001368813, NP_001368814, NP_001368815, NP_001368816, NP_001368817, NP_001368818, NP_001368819, NP_001986* (*=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
IPR045311	LC-FACS_euk	Family

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), 11 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)
• 3,7,11,15-tetramethylhexadecanoate + ATP + CoA = phytanoyl-CoA + AMP + diphosphate (RHEA:21380)
• hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate (RHEA:30751)
• (9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate (RHEA:33607)
• (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate (RHEA:36139)
• 2,6,10,14-tetramethylpentadecanoate + ATP + CoA = pristanoyl-CoA + AMP + diphosphate (RHEA:47264)
• 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate (RHEA:52016)
• 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 (25 total): sequence conflict 11, modified residue 8, splice variant 2, chain 1, transmembrane region 1, glycosylation site 1, topological domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33121-F1	90.16	0.71

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 (8): 632, 1, 9, 84, 207, 356, 386, 620

Glycosylation sites (1): 135

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2046105	Linoleic acid (LA) metabolism
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-1430728	Metabolism
R-HSA-2046104	alpha-linolenic (omega3) and linoleic (omega6) acid metabolism
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-74160	Gene expression (Transcription)
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-8978868	Fatty acid metabolism
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 569 (showing top): REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, MODULE_92, KOBAYASHI_EGFR_SIGNALING_24HR_UP, MCLACHLAN_DENTAL_CARIES_UP, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, MODULE_255, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, PEREZ_TP63_TARGETS, MODULE_45, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MODULE_317, IVANOVA_HEMATOPOIESIS_MATURE_CELL

GO Biological Process (18): very long-chain fatty acid metabolic process (GO:0000038), long-chain fatty acid metabolic process (GO:0001676), fatty acid biosynthetic process (GO:0006633), response to nutrient (GO:0007584), lipid biosynthetic process (GO:0008610), positive regulation of long-chain fatty acid import across plasma membrane (GO:0010747), fatty acid transport (GO:0015908), triglyceride biosynthetic process (GO:0019432), adiponectin-activated signaling pathway (GO:0033211), response to oleic acid (GO:0034201), long-chain fatty-acyl-CoA biosynthetic process (GO:0035338), xenobiotic catabolic process (GO:0042178), linoleic acid metabolic process (GO:0043651), long-chain fatty acid import into cell (GO:0044539), positive regulation of cold-induced thermogenesis (GO:0120162), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), response to xenobiotic stimulus (GO:0009410)

GO Molecular Function (10): long-chain fatty acid-CoA ligase activity (GO:0004467), ATP binding (GO:0005524), protein serine/threonine kinase activator activity (GO:0043539), arachidonate-CoA ligase activity (GO:0047676), phytanate-CoA ligase activity (GO:0050197), pristanate-CoA ligase activity (GO:0070251), palmitoyl-CoA ligase activity (GO:0090433), oleoyl-CoA ligase activity (GO:0090434), nucleotide binding (GO:0000166), ligase activity (GO:0016874)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), peroxisomal membrane (GO:0005778), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), peroxisome (GO:0005777)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	2
Fatty acid metabolism	2
Metabolism of lipids	2
Regulation of lipid metabolism by PPARalpha	1
Fatty acyl-CoA biosynthesis	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Gene expression (Transcription)	1
Metabolism	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid metabolic process	3
long-chain fatty acid-CoA ligase activity	3
response to chemical	2
lipid metabolic process	2
long-chain fatty acid metabolic process	2
CoA-ligase activity	2
cytoplasm	2
intracellular membrane-bounded organelle	2
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
response to nutrient levels	1
biosynthetic process	1
regulation of long-chain fatty acid import across plasma membrane	1
long-chain fatty acid import across plasma membrane	1
positive regulation of transmembrane transport	1
positive regulation of long-chain fatty acid import into cell	1
lipid transport	1
monocarboxylic acid transport	1
triglyceride metabolic process	1
acylglycerol biosynthetic process	1
hormone-mediated signaling pathway	1
cytokine-mediated signaling pathway	1
response to fatty acid	1
long-chain fatty-acyl-CoA metabolic process	1
fatty-acyl-CoA biosynthetic process	1
xenobiotic metabolic process	1
catabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
long-chain fatty acid transport	1
import into cell	1
lipid import into cell	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid-CoA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

3048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSL1	AASDH	Q4L235	938
ACSL1	CPT1A	P50416	933
ACSL1	SLC27A2	O14975	886
ACSL1	SLC27A6	Q9Y2P4	857
ACSL1	DGAT1	O75907	852
ACSL1	CD36	P16671	828
ACSL1	SCARB2	Q14108	818
ACSL1	ACADL	P28330	815
ACSL1	SCARB1	Q8WTV0	808
ACSL1	SLC27A1	Q6PCB7	806
ACSL1	ACACA	Q13085	793
ACSL1	SLC27A4	Q6P1M0	791
ACSL1	FASN	P49327	791
ACSL1	ACADVL	P49748	779
ACSL1	ACAA2	P42765	760

IntAct

83 interactions, top by confidence:

A	B	Type	Score
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
NR3C2	ACSL1	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NMES1	COX7A2L	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CTDP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
HLA-DPB1	TAPBP	psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
KLRK1	NRDC	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (93): ACSL1 (Affinity Capture-MS), ACSL1 (Affinity Capture-MS), ACSL1 (Affinity Capture-MS), ACSL1 (Affinity Capture-MS), BDH1 (Affinity Capture-MS), ACSL1 (Affinity Capture-RNA), ACSL1 (Affinity Capture-MS), ACSL1 (Affinity Capture-MS), ACSL1 (Affinity Capture-MS), ACSL1 (Affinity Capture-MS), ACSL1 (Affinity Capture-RNA), ACSL1 (Affinity Capture-MS), ACSL1 (Negative Genetic), ACSL1 (Negative Genetic), ACSL1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0U1WZ18, A3QK15, B9N1F9, D3ZVR9, E0CSI1, O70196, P00503, P00504, P05201, P08906, P33121, P33124, P40142, P50137, P50554, P54767, P61922, P78330, P80147, Q07346, Q14410, Q15124, Q1W377, Q28BL6, Q2KHU0, Q2KIG0, Q42472, Q42521, Q4R4D5, Q4R5L1, Q5R691, Q5RB83, Q5ZLG0, Q6P1N9, Q6P8M1, Q7TN78, Q80W40, Q86V21, Q8BZF8, Q8K183

Diamond homologs: A0A0C1E5J8, A0A0L1JF11, A0A0S6XHH0, A0A125SUR3, A0A166YZW0, A0A1L9NGU5, A0A1L9U7P9, A0A1L9WUW3, A0A1M3T4K3, A0A1R3RGK1, A0A1W6BT46, A0A1W6BT53, A0A2I1D2N0, A0A2I2F262, A0A2V5H0B0, A0A2Z5UHX0, A0A317VEE1, A0A318Z3U0, A0A319A6V2, A0A319BQC1, A0A319DV72, A0A395I3F8, A0A455ZJD4, A0A5K6CNB8, A0A6G9KH54, A0A823A1C6, A0AAN4PB13, A1DN09, A2QYX4, A2R6H0, A2TBU4, B0CN26, B2KWH8, B6HJU6, B6HLP9, B8NHE4, B8NI19, B8NR69, C9K7C1, E9FCP4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PPARA	“up-regulates quantity by expression”	ACSL1	“transcriptional regulation”
ACSL1	“up-regulates quantity”	palmitoyl-CoA	“chemical modification”
ACSL1	“down-regulates quantity”	“hexadecanoic acid”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	46
Likely pathogenic	4
Uncertain significance	75
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
144226	GRCh38/hg38 4q35.1-35.2(chr4:184327081-189975519)x3	Pathogenic
144872	GRCh38/hg38 4q35.1-35.2(chr4:182437091-190018185)x1	Pathogenic
146879	GRCh38/hg38 4q34.1-35.2(chr4:173854560-189548183)x1	Pathogenic
147808	GRCh38/hg38 4q35.1-35.2(chr4:184239531-189975519)x1	Pathogenic
148007	GRCh38/hg38 4q34.3-35.2(chr4:177985956-189975519)x1	Pathogenic
148187	GRCh38/hg38 4q34.3-35.2(chr4:178549472-190095391)x1	Pathogenic
148268	GRCh38/hg38 4q34.3-35.2(chr4:178014570-190095391)x1	Pathogenic
148270	GRCh38/hg38 4q34.3-35.2(chr4:180574962-190095391)x1	Pathogenic
149694	GRCh38/hg38 4q35.1-35.2(chr4:183072743-190095391)x1	Pathogenic
151757	GRCh38/hg38 4q34.3-35.2(chr4:179295511-190036318)x3	Pathogenic
1527143	GRCh37/hg19 4q35.1-35.2(chr4:185381293-190957473)	Pathogenic
155012	GRCh38/hg38 4q34.1-35.2(chr4:172501374-190095332)x1	Pathogenic
155165	GRCh38/hg38 4q33-35.2(chr4:170899124-190036318)x1	Pathogenic
161066	GRCh38/hg38 4q34.3-35.1(chr4:181579626-186100199)x1	Pathogenic
1704649	GRCh37/hg19 4q34.1-35.2(chr4:174944132-190957473)x1	Pathogenic
1710924	GRCh37/hg19 4q35.1-35.2(chr4:185211271-190957473)x1	Pathogenic
1807820	GRCh37/hg19 4q35.1-35.2(chr4:183694501-190957473)x1	Pathogenic
253406	GRCh37/hg19 4q34.3-35.2(chr4:178243625-190713650)x1	Pathogenic
253508	GRCh37/hg19 4q34.1-35.2(chr4:176270886-190713650)x1	Pathogenic
2671582	Single allele	Pathogenic
3062775	GRCh37/hg19 4q34.1-35.1(chr4:175496275-186495932)x1	Pathogenic
33229	GRCh38/hg38 4q34.3-35.1(chr4:181579626-186100199)x1	Pathogenic
3391886	GRCh37/hg19 4q34.3-35.2(chr4:179475329-190957473)x1	Pathogenic
394376	GRCh37/hg19 4q35.1-35.2(chr4:185253508-190713591)x1	Pathogenic
442869	GRCh37/hg19 4q34.3-35.2(chr4:180702769-190957473)x3	Pathogenic
443369	GRCh37/hg19 4q34.2-35.2(chr4:176306103-190957473)x3	Pathogenic
4682607	GRCh37/hg19 4q35.1-35.2(chr4:184213971-190957473)x1	Pathogenic
560041	Single allele	Pathogenic
563003	GRCh37/hg19 4q34.1-35.2(chr4:175709188-190957473)x1	Pathogenic
563004	GRCh37/hg19 4q34.2-35.2(chr4:176493246-190957473)x1	Pathogenic

SpliceAI

3674 predictions. Top by Δscore:

Variant	Effect	Δscore
4:184757633:ACCT:A	donor_loss	1.0000
4:184757703:CATC:C	acceptor_gain	1.0000
4:184757704:ATC:A	acceptor_gain	1.0000
4:184757705:TC:T	acceptor_gain	1.0000
4:184757706:CC:C	acceptor_gain	1.0000
4:184757706:CCT:C	acceptor_loss	1.0000
4:184757707:C:CC	acceptor_gain	1.0000
4:184757707:CT:C	acceptor_loss	1.0000
4:184757708:T:C	acceptor_loss	1.0000
4:184757900:C:CT	acceptor_gain	1.0000
4:184757905:T:TC	acceptor_gain	1.0000
4:184760353:ATAC:A	donor_loss	1.0000
4:184760354:TA:T	donor_loss	1.0000
4:184760355:A:AC	donor_gain	1.0000
4:184760356:C:CC	donor_gain	1.0000
4:184760356:CCTG:C	donor_gain	1.0000
4:184760496:CCATT:C	acceptor_gain	1.0000
4:184760497:CATT:C	acceptor_gain	1.0000
4:184760497:CATTC:C	acceptor_gain	1.0000
4:184760499:TT:T	acceptor_gain	1.0000
4:184760499:TTCTG:T	acceptor_loss	1.0000
4:184760500:TC:T	acceptor_loss	1.0000
4:184760501:C:CC	acceptor_gain	1.0000
4:184760501:CT:C	acceptor_loss	1.0000
4:184760502:T:A	acceptor_loss	1.0000
4:184762402:CTT:C	donor_loss	1.0000
4:184762403:TTACT:T	donor_loss	1.0000
4:184762404:TACTG:T	donor_loss	1.0000
4:184762405:A:AC	donor_gain	1.0000
4:184762406:C:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003701 (4:184780151 C>T), RS1000054049 (4:184816313 C>G,T), RS1000062018 (4:184803556 G>A), RS1000133894 (4:184809648 T>C), RS1000192334 (4:184821376 G>C), RS1000192652 (4:184765711 A>G), RS1000201306 (4:184784329 C>T), RS10002538 (4:184768833 G>A,C), RS1000257419 (4:184756052 T>A,C), RS1000284555 (4:184794998 G>A), RS1000293455 (4:184801049 C>T), RS1000330610 (4:184775617 G>A), RS1000349532 (4:184762169 A>C), RS10003568 (4:184815160 T>C,G), RS1000362694 (4:184790215 A>G)

Disease associations

OMIM: gene MIM:152425 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003542_35	Night sleep phenotypes	6.000000e-06
GCST004773_1	Type 2 diabetes	2.000000e-10
GCST006867_37	Type 2 diabetes	2.000000e-11
GCST007433_2	Fulminant type 1 diabetes	4.000000e-06
GCST009379_269	Type 2 diabetes	1.000000e-13
GCST010152_4	Neuroblastoma or malignant cutaneous melanoma	5.000000e-06
GCST90002395_660	Mean platelet volume	5.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295746 (SINGLE PROTEIN)

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

ChEMBL bioactivities

26 potent at pChembl≥5 of 32 total, top 26 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL4764916
8.18	Kd	6.58	nM	CHEMBL5653589
8.18	ED50	6.58	nM	CHEMBL5653589
7.89	IC50	13	nM	CHEMBL4750346
7.89	IC50	13	nM	CHEMBL4746996
7.55	IC50	28	nM	CHEMBL4787746
7.47	IC50	34	nM	CHEMBL4749130
7.41	IC50	39	nM	CHEMBL4781788
7.38	IC50	42	nM	CHEMBL4778736
7.36	IC50	44	nM	CHEMBL4797544
7.35	IC50	45	nM	CHEMBL4755109
7.33	IC50	47	nM	CHEMBL4748671
7.33	IC50	47	nM	CHEMBL4740366
6.82	IC50	150	nM	CHEMBL4783346
6.72	IC50	190	nM	CHEMBL4800541
6.62	IC50	240	nM	CHEMBL4757253
6.62	IC50	240	nM	CHEMBL4761388
6.51	IC50	310	nM	CHEMBL4776019
6.40	IC50	400	nM	CHEMBL4757057
6.22	IC50	600	nM	CHEMBL4748493
6.02	IC50	950	nM	CHEMBL4751045
5.77	IC50	1700	nM	CHEMBL222502
5.72	IC50	1900	nM	CHEMBL4787809
5.36	IC50	4400	nM	CHEMBL4800499
5.34	IC50	4600	nM	CHEMBL4746718
5.11	IC50	7800	nM	CHEMBL4752206

PubChem BioAssay actives

25 with measured affinity, of 42 total; 24 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
2-(2,3-dihydro-1-benzofuran-6-ylmethyl)-5-[4-fluoro-4-(2H-tetrazol-5-yl)cyclohexyl]oxy-1-methylbenzimidazole	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0030	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147789: Binding affinity to human ACSL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0066	uM
4-[2-(2,3-dihydro-1-benzofuran-6-ylmethyl)-1-methylbenzimidazol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0130	uM
5-[4-fluoro-4-(2H-tetrazol-5-yl)cyclohexyl]oxy-1-methyl-2-[(3-methylphenyl)methyl]benzimidazole	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0130	uM
4-[7-chloro-1-methyl-2-[(3-methylphenyl)methyl]benzimidazol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0280	uM
1-methyl-2-[(3-methylphenyl)methyl]-5-[4-(2H-tetrazol-5-yl)cyclohexyl]oxybenzimidazole	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0340	uM
4-[[2-[(3-methylphenyl)methyl]-1,3-benzoxazol-5-yl]oxy]cyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0390	uM
4-[1-methyl-2-[(3-methylphenyl)methyl]benzimidazol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0420	uM
4-[1-methyl-2-[(3-methylphenyl)methyl]imidazo[4,5-b]pyridin-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0440	uM
4-[3-methyl-2-[(3-methylphenyl)methyl]indazol-6-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0450	uM
4-[6-chloro-1-methyl-2-[(3-methylphenyl)methyl]benzimidazol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0470	uM
3-[4-[1-methyl-2-[(3-methylphenyl)methyl]benzimidazol-5-yl]oxycyclohexyl]-4H-1,2,4-oxadiazol-5-one	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.0470	uM
4-[1-methyl-2-[(4-methylphenyl)methyl]benzimidazol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.1500	uM
4-[1-methyl-2-[[3-(trifluoromethyl)phenyl]methyl]benzimidazol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.1900	uM
4-(9-oxoxanthen-2-yl)oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.2400	uM
7-(9-oxoxanthen-2-yl)oxyheptanoic acid	1684049: Inhibition of ACSL1 (unknown origin) assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.3100	uM
4-[1-methyl-2-[(3-methylphenyl)methyl]indol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.4000	uM
4-[3-carbamoyl-1-methyl-2-[(3-methylphenyl)methyl]indol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.6000	uM
4-[1-methyl-2-[(3-methylphenyl)methyl]benzimidazol-5-yl]oxycyclohexane-1-carboxamide	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	0.9500	uM
5-(9-oxoxanthen-2-yl)oxypentanoic acid	1684049: Inhibition of ACSL1 (unknown origin) assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	1.7000	uM
4-[3-cyano-1-methyl-2-[(3-methylphenyl)methyl]indol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	1.9000	uM
4-[(2-phenyl-1,3-benzoxazol-5-yl)oxy]cyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	4.4000	uM
4-(9H-xanthen-2-yloxy)cyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	4.6000	uM
4-[1-methyl-2-[(2-methylphenyl)methyl]benzimidazol-5-yl]oxycyclohexane-1-carboxylic acid	1684048: Inhibition of recombinant human ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis	ic50	7.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression, decreases expression	6
Cyclosporine	increases expression, affects cotreatment, affects expression, decreases expression, decreases methylation	5
bisphenol A	increases methylation, increases expression, decreases expression, affects cotreatment	4
perfluorooctanoic acid	increases expression	4
Estradiol	affects cotreatment, increases expression, decreases expression	4
Progesterone	affects cotreatment, increases expression	4
Tetrachlorodibenzodioxin	increases reaction, decreases expression, affects binding	4
Cadmium Chloride	increases abundance, increases expression, decreases expression	4
Acetaminophen	increases expression, affects cotreatment, decreases expression	3
Oxygen	increases expression, decreases expression, decreases reaction	3
sulforaphane	increases expression	2
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Zoledronic Acid	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzene	affects expression	2
Bezafibrate	increases expression	2
Cisplatin	decreases expression, increases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Fenofibrate	increases expression, increases reaction	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases expression	2
Palmitic Acid	affects cotreatment, decreases expression, affects expression	2
bisphenol F	affects cotreatment, decreases expression	1
bisphenol E	decreases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118983	Binding	Binding affinity to ACSL1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1IV	Abcam HeLa ACSL1 KO	Cancer cell line	Female
CVCL_E0TH	Ubigene Hep G2 ACSL1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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