ACSL5

Summary

ACSL5 (acyl-CoA synthetase long chain family member 5, HGNC:16526) is a protein-coding gene on chromosome 10q25.2, encoding Long-chain-fatty-acid–CoA ligase 5 (Q9ULC5). 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. This isozyme is highly expressed in uterus and spleen, and in trace amounts in normal brain, but has markedly increased levels in malignant gliomas. This gene functions in mediating fatty acid-induced glioma cell growth. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 51703 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diarrhea 13 (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 121 total — 2 pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_203379

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16526
Approved symbol	ACSL5
Name	acyl-CoA synthetase long chain family member 5
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Aliases	ACS5, ACS2
Ensembl gene	ENSG00000197142
Ensembl biotype	protein_coding
OMIM	605677
Entrez	51703

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 35 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000354273, ENST00000354655, ENST00000356116, ENST00000393081, ENST00000433418, ENST00000467340, ENST00000495539, ENST00000496328, ENST00000861349, ENST00000861350, ENST00000861351, ENST00000861352, ENST00000861353, ENST00000861354, ENST00000861355, ENST00000861356, ENST00000861357, ENST00000861358, ENST00000861359, ENST00000861360, ENST00000861361, ENST00000861362, ENST00000861363, ENST00000861364, ENST00000861365, ENST00000861366, ENST00000861367, ENST00000861368, ENST00000861369, ENST00000954829, ENST00000954830, ENST00000954831, ENST00000954832, ENST00000954833, ENST00000954834, ENST00000954835, ENST00000954836, ENST00000954837

RefSeq mRNA: 4 — MANE Select: NM_203379 NM_001387037, NM_016234, NM_203379, NM_203380

CCDS: CCDS7572, CCDS7573, CCDS91344

Canonical transcript exons

ENST00000354655 — 21 exons

Exon	Start	End
ENSE00000724257	112409507	112409685
ENSE00001000193	112411456	112411529
ENSE00001096563	112426258	112426359
ENSE00001096573	112421593	112421665
ENSE00001096575	112421947	112422035
ENSE00001096579	112426788	112426859
ENSE00001411902	112374116	112374269
ENSE00001835863	112427218	112428376
ENSE00003470738	112422325	112422441
ENSE00003482344	112416888	112417022
ENSE00003484218	112410463	112410495
ENSE00003492611	112394918	112395102
ENSE00003541113	112413173	112413307
ENSE00003572499	112425338	112425481
ENSE00003589092	112408422	112408521
ENSE00003619593	112411902	112411979
ENSE00003623182	112410584	112410635
ENSE00003638097	112398901	112399009
ENSE00003652803	112404511	112404575
ENSE00003661740	112417846	112417941
ENSE00003671255	112404705	112404806

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.4060 / max 2111.1540, expressed in 1151 samples.

FANTOM5 promoters (28 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107050	15.4339	1057
107037	1.8070	79
107051	1.5061	328
107036	1.0733	53
107041	1.0643	273
107042	0.8578	220
107052	0.2445	44
107060	0.2000	41
107040	0.1686	65
107043	0.1630	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.90	gold quality
ileal mucosa	UBERON:0000331	99.27	gold quality
corpus epididymis	UBERON:0004359	99.12	gold quality
rectum	UBERON:0001052	98.47	gold quality
mucosa of transverse colon	UBERON:0004991	98.18	gold quality
colonic mucosa	UBERON:0000317	97.97	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.73	gold quality
duodenum	UBERON:0002114	97.37	gold quality
right lobe of liver	UBERON:0001114	96.43	gold quality
endometrium	UBERON:0001295	96.17	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.08	gold quality
small intestine	UBERON:0002108	95.40	gold quality
right uterine tube	UBERON:0001302	94.83	gold quality
liver	UBERON:0002107	94.60	gold quality
granulocyte	CL:0000094	94.46	gold quality
transverse colon	UBERON:0001157	94.27	gold quality
caput epididymis	UBERON:0004358	94.14	gold quality
upper lobe of left lung	UBERON:0008952	93.38	gold quality
upper lobe of lung	UBERON:0008948	93.28	gold quality
vermiform appendix	UBERON:0001154	93.04	gold quality
gall bladder	UBERON:0002110	92.54	gold quality
monocyte	CL:0000576	92.30	gold quality
leukocyte	CL:0000738	92.25	gold quality
mononuclear cell	CL:0000842	92.13	gold quality
colonic epithelium	UBERON:0000397	91.90	gold quality
intestine	UBERON:0000160	91.46	gold quality
caecum	UBERON:0001153	91.41	gold quality
right lung	UBERON:0002167	91.21	gold quality
lower lobe of lung	UBERON:0008949	91.12	gold quality
omental fat pad	UBERON:0010414	91.03	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	51.69
E-ANND-3	yes	18.62
E-MTAB-6142	no	121.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ERF, FOXO1, MYOD1, SREBF1, TCF12

miRNA regulators (miRDB)

52 targeting ACSL5, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4520-2-3P	99.14	69.28	1009

Literature-anchored findings (GeneRIF, showing 35)

• expression of ACS5 in the gastric body and the small intestine with metaplasia or heterotopia (PMID:15736044)
• ACS5 is a very suitable marker molecule for the detection of villus atrophy in the small intestine. (PMID:15809837)
• SREBP-1c-mediated insulin regulation of acyl-CoA synthestase 5 expression indicate that ACS-5 is involved in the anabolic fate of fatty acids. (PMID:16198472)
• Existence of a link between ACSL5 genotype and diet responsiveness. (PMID:17495181)
• Suggest an ACSL5-dependent regulatory mechanism that contributes to the cellular renewal along the crypt-villus axis in human small intestine. (PMID:17681178)
• Oncostatin M directly lowers the plasma triglycerides in hyperlipidemia by stimulating the transcription of ACSL3/5 in the liver. (PMID:17761945)
• Expression of ACSL5 in human epidermis is reported. (PMID:18228202)
• These results indicate that ACSL5 is a critical factor for survival of glioma cells under acidic tumor microenvironment. (PMID:18806831)
• These results reveal a mechanism for elevated transcription of ACSL5 in skeletal muscle of carriers of the rs2419621(T) allele, associated with more rapid diet-induced weight loss. (PMID:19218499)
• Increased ACSL5 is associated with Fatty Liver. (PMID:20470896)
• High ACSL5 transcript levels associate with systemic lupus erythematosus and apoptosis in Jurkat T lymphocytes and peripheral blood cells (PMID:22163040)
• The data strongly indicate that human but not rat acyl-CoA synthetase 5 is sensitive to triacsin C and does not compensate for other triacsin C-sensitive ACSL isoforms. (PMID:22171129)
• Levels of acyl-coenzyme A synthetase 5 in urothelial cells and corresponding neoplasias reflect cellular differentiation. (PMID:23348389)
• Down-regulation of ACSL5 is associated with colorectal cancer. (PMID:24222123)
• Uncoupling of ACSL5 and mitochondrial mortalin by mutated TP53 could be important in colorectal carcinogenesis. (PMID:24770931)
• ACSL5 mediates antiproliferative activities via Wnt2B palmitoylation with diminished Wnt activity. The molecular pathway is probably relevant for intestinal homeostasis, overwhelmed by other pathways in carcinogenesis. (PMID:25356045)
• Functional variant (rs2256368:A>G) affecting ACSL5 exon 20 skipping was identified as a causal factor linked to the migraine-associated rs12355831:A>G, suggesting that the activation of long-chain fatty acids by the spliced ACSL5-Delta20 molecules is involved in migraine pathology. (PMID:27189022)
• colorectal adenocarcinomas with low (n=41; group 1) or high (n=31; group 2) ACSL5 levels were identified. In a one-year follow-up, tumour recurrence was significantly increased in group 1. (PMID:28153554)
• 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)
• our study has demonstrated that ACS5 expression was increased in colorectal cancer (CRC) cells and CRC tissues and its upregulation closely correlated to poor tumor differentiation and excess muscular layer in patients with CRC (PMID:28808653)
• rs2419621 T allele carriers are more responsive to lifestyle interventions partly due to an increase in the short ACSL5 protein isoform, increasing cellular, tissue and whole-body fatty acid utilization. (PMID:29605434)
• downregulation of ACSL5 and Wnt2B could play an important role in the development of bronchial-alveolar structures in congenital pulmonary airway malformations (CPAMs). (PMID:30463708)
• Our findings reveal that LOX and ACSL5 are potential prognostic markers for the prognosis of pancreatic cancer patients. (PMID:30712446)
• Our findings indicate that the variant rs2256368:A>G can predict a growth inhibitory activity, caused by the Spl isoform of ACSL5 protein, opposed to the activity of the NSpl. Deep understanding of its functioning might have application in metabolic diseases and cancer. (PMID:31053784)
• miR-497-5p mediates starvation-induced death in colon cancer cells by targeting acyl-CoA synthetase-5 and modulation of lipid metabolism. (PMID:32012265)
• ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric cancer and triggers ACSL5. (PMID:32129880)
• Roles of acyl-CoA synthetase long-chain family member 5 and colony stimulating factor 2 in inhibition of palmitic or stearic acids in lung cancer cell proliferation and metabolism. (PMID:32347412)
• ACYL-CoA synthetase long-chain 5 polymorphism is associated with weight loss and metabolic changes in response to a partial meal-replacement hypocaloric diet.", trans “El polimorfismo de la ACYL-CoA-sintetasa de cadena larga 5 se asocia a perdida de peso y cambios metabolicos en respuesta a una dieta hipocalorica parcial de reemplazo. (PMID:32686444)
• A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis. (PMID:32968195)
• Deficiency of acyl-CoA synthetase 5 is associated with a severe and treatable failure to thrive of neonatal onset. (PMID:33191500)
• The gene variant rs2419621 of ACYL-CoA synthetase long-chain 5 gene is associated with weight loss and metabolic changes in response to a robotic sleeve gastrectomy in morbid obese subjects. (PMID:34859867)
• Lysophosphatidylcholine inhibits lung cancer cell proliferation by regulating fatty acid metabolism enzyme long-chain acyl-coenzyme A synthase 5. (PMID:36639836)
• More than just a histone deacetylase: cytoplasmic SIRT6 facilitates fatty acid oxidation through ACSL5 deacetylation. (PMID:36880305)
• Hypoxia-responsive PPARGC1A/BAMBI/ACSL5 axis promotes progression and resistance to lenvatinib in hepatocellular carcinoma. (PMID:36932115)
• ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/beta-catenin signaling by palmitoylation modification. (PMID:37131085)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acsl5	ENSDARG00000075931
mus_musculus	Acsl5	ENSMUSG00000024981
rattus_norvegicus	Acsl5	ENSRNOG00000016265
drosophila_melanogaster	CG3961	FBGN0036821
caenorhabditis_elegans	acs-13	WBGENE00022037

Paralogs (12): ACSL4 (ENSG00000068366), SLC27A5 (ENSG00000083807), ACSBG1 (ENSG00000103740), SLC27A6 (ENSG00000113396), ACSL3 (ENSG00000123983), SLC27A1 (ENSG00000130304), ACSBG2 (ENSG00000130377), SLC27A2 (ENSG00000140284), SLC27A3 (ENSG00000143554), ACSL1 (ENSG00000151726), ACSL6 (ENSG00000164398), SLC27A4 (ENSG00000167114)

Protein

Protein identifiers

Long-chain-fatty-acid–CoA ligase 5 — Q9ULC5 (reviewed: Q9ULC5)

Alternative names: Arachidonate–CoA ligase, Long-chain acyl-CoA synthetase 5

All UniProt accessions (4): A0A804HIN9, A0A8C8KCK5, A0A8C8L3F5, Q9ULC5

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. ACSL5 may activate fatty acids from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage. Utilizes a wide range of saturated fatty acids with a preference for C16-C18 unsaturated fatty acids. It was suggested that it may also stimulate fatty acid oxidation. At the villus tip of the crypt-villus axis of the small intestine may sensitize epithelial cells to apoptosis specifically triggered by the death ligand TRAIL. May have a role in the survival of glioma cells.

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

Disease relevance. Diarrhea 13 (DIAR13) [MIM:620357] An autosomal recessive disorder characterized by neonatal onset of recurrent vomiting and diarrhea, leading to severe failure to thrive. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. Localize in mitochondrion and endoplasmic reticulum. Localize in mitochondrion and endoplasmic reticulum.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9ULC5-1	1, ACSL5b, ACSL5-fl	yes
Q9ULC5-3	2, ACSL5a
Q9ULC5-4	3, ACSL5delta20

RefSeq proteins (4): NP_001373966, NP_057318, NP_976313, NP_976314 (=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

Catalyzed reactions (Rhea), 10 shown:

• a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate (RHEA:15421)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate (RHEA:19713)
• hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate (RHEA:30751)
• (9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate (RHEA:33607)
• (E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate (RHEA:36139)
• 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate (RHEA:52012)
• 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate (RHEA:52016)
• 5-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 (12 total): sequence variant 5, modified residue 2, splice variant 2, chain 1, transmembrane region 1, topological domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULC5-F1	90.55	0.69

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 (2): 32, 361

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 323 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, CEBPB_01

GO Biological Process (6): long-chain fatty acid metabolic process (GO:0001676), positive regulation of long-chain fatty acid import across plasma membrane (GO:0010747), long-chain fatty-acyl-CoA biosynthetic process (GO:0035338), regulation of extrinsic apoptotic signaling pathway (GO:2001236), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (7): long-chain fatty acid-CoA ligase activity (GO:0004467), ATP binding (GO:0005524), arachidonate-CoA ligase activity (GO:0047676), oleoyl-CoA ligase activity (GO:0090434), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (8): nucleoplasm (GO:0005654), nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Fatty acyl-CoA biosynthesis	1
Metabolism	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
long-chain fatty acid-CoA ligase activity	2
nuclear lumen	2
cellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
fatty acid metabolic 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
long-chain fatty-acyl-CoA metabolic process	1
fatty-acyl-CoA biosynthetic process	1
extrinsic apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
long-chain fatty acid metabolic process	1
fatty acid-CoA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membraneless organelle	1
mitochondrial membrane	1
organelle outer membrane	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSL5	AASDH	Q4L235	906
ACSL5	CPT1A	P50416	873
ACSL5	DGAT1	O75907	832
ACSL5	DGAT2	Q96PD7	815
ACSL5	SLC27A1	Q6PCB7	725
ACSL5	TLCD3B	Q71RH2	703
ACSL5	ABCD3	P28288	655
ACSL5	CD36	P16671	641
ACSL5	AWAT1	Q58HT5	638
ACSL5	ABCD1	P33897	622
ACSL5	ACSS1	Q9NUB1	619
ACSL5	SCARB2	Q14108	608
ACSL5	HADHB	P55084	597
ACSL5	SCARB1	Q8WTV0	595
ACSL5	RUNX1	Q01196	583

IntAct

59 interactions, top by confidence:

A	B	Type	Score
ACSL5	AQP6	psi-mi:“MI:0915”(physical association)	0.560
RETREG3	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
SLC35C2	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
SLC16A7	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
SLC7A14	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
PEX12	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
AQP6	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
SELI	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
ACSL5	CREB3	psi-mi:“MI:0915”(physical association)	0.370
FAM136A	IDE	psi-mi:“MI:0914”(association)	0.350
CHCHD10	ACSL4	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
PTPMT1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
CHCHD10	AKR7A2	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
ELK1	TPP1	psi-mi:“MI:0914”(association)	0.350
PAK1		psi-mi:“MI:0914”(association)	0.350
PRKCB	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
PEBP1	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
CAV2	SURF4	psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): ACSL5 (Two-hybrid), ACSL5 (Affinity Capture-MS), ACSL5 (Affinity Capture-MS), ACSL5 (Affinity Capture-MS), ACSL5 (Biochemical Activity), ACSL5 (Affinity Capture-MS), ACSL5 (Affinity Capture-MS), ACSL5 (Two-hybrid), ACSL5 (Two-hybrid), ACSL5 (Two-hybrid), ACSL5 (Two-hybrid), ACSL5 (Two-hybrid), ACSL5 (Two-hybrid), ACSL5 (Two-hybrid), ACSL5 (Two-hybrid)

ESM2 similar proteins: A0A2H5AIX5, A0A2H5AIY4, A0A6B9HER0, I3PB37, M4IQR7, M4IQS1, M4IRL6, M4ISH0, O24145, O24146, O24540, O35547, O60488, O88813, O95573, P0C5B6, P13129, P14912, P14913, P31684, P31685, P31686, P31687, Q0DV32, Q0P4F7, Q10S72, Q26304, Q27757, Q3E6Y4, Q42524, Q54P77, Q54P78, Q5R668, Q63151, Q84P21, Q84P23, Q84P24, Q84P25, Q84P26, Q8JZR0

Diamond homologs: A0A017SQ41, A0A0A1EA36, A0A0C1E6T8, A0A0H2ZGJ4, A0A179H164, A0A1B2CTC5, A0A1E3B0T2, A0A1L9NGU5, A0A1L9U7P9, A0A1M3T4K3, A0A1U9YHZ2, A0A2I2F262, A0A317VEE1, A0A318Z3U0, A0A319A6V2, A0A319BQC1, A0A395I3F8, A0A5K6CNB8, A2QYX4, A8M6W3, A8NS27, A8NVB7, B0CN26, B0XWK8, B6HLU1, B8NY88, D4AU31, D9XF47, D9XF49, G3XNF4, G3XUF0, G7XQ31, M1WCQ3, O30408, O30409, O31782, O31827, O68007, O68008, O88813

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ACSL5	“up-regulates quantity”	“long-chain fatty acyl-CoA(4-)”	“chemical modification”
ACSL5	“down-regulates quantity”	“long-chain fatty acid anion”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	85
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1527599	GRCh37/hg19 10q24.32-25.3(chr10:104030479-115410590)	Pathogenic
2500167	NM_203379.2(ACSL5):c.1358C>A (p.Thr453Lys)	Pathogenic

SpliceAI

3032 predictions. Top by Δscore:

Variant	Effect	Δscore
10:112404844:GGT:G	donor_gain	1.0000
10:112408520:GG:G	donor_gain	1.0000
10:112408521:GG:G	donor_gain	1.0000
10:112409497:T:TA	acceptor_gain	1.0000
10:112409502:TCCA:T	acceptor_loss	1.0000
10:112409503:CCAG:C	acceptor_loss	1.0000
10:112409504:CAGC:C	acceptor_loss	1.0000
10:112409505:A:AG	acceptor_gain	1.0000
10:112409505:AGCT:A	acceptor_gain	1.0000
10:112409506:G:GC	acceptor_gain	1.0000
10:112409506:G:GT	acceptor_loss	1.0000
10:112409506:GCT:G	acceptor_gain	1.0000
10:112409506:GCTG:G	acceptor_gain	1.0000
10:112410444:T:A	acceptor_gain	1.0000
10:112410453:A:AG	acceptor_gain	1.0000
10:112410457:A:AG	acceptor_gain	1.0000
10:112410460:T:G	acceptor_gain	1.0000
10:112410461:A:AG	acceptor_gain	1.0000
10:112410462:G:GG	acceptor_gain	1.0000
10:112411890:T:TA	acceptor_gain	1.0000
10:112413168:TTCA:T	acceptor_loss	1.0000
10:112413170:CA:C	acceptor_loss	1.0000
10:112413171:A:AG	acceptor_gain	1.0000
10:112413171:AG:A	acceptor_gain	1.0000
10:112413171:AGGCT:A	acceptor_gain	1.0000
10:112413172:G:A	acceptor_loss	1.0000
10:112413172:G:GA	acceptor_gain	1.0000
10:112413172:GG:G	acceptor_gain	1.0000
10:112413172:GGC:G	acceptor_gain	1.0000
10:112413172:GGCT:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017846 (10:112424036 T>C,G), RS1000080668 (10:112418745 G>A), RS1000110394 (10:112406161 C>G), RS1000134499 (10:112418506 C>G,T), RS1000171609 (10:112372529 G>A), RS1000171729 (10:112376258 C>G,T), RS1000176450 (10:112407457 C>T), RS1000182437 (10:112420513 G>A), RS1000202805 (10:112375909 T>C), RS1000232174 (10:112406386 A>G,T), RS1000256247 (10:112412082 G>A,T), RS1000328188 (10:112397969 C>T), RS1000355422 (10:112427579 G>C), RS1000355827 (10:112382639 A>G), RS1000407957 (10:112427931 T>A)

Disease associations

OMIM: gene MIM:605677 | disease phenotypes: MIM:620357

GenCC curated gene-disease

Disease	Classification	Inheritance
diarrhea 13	Limited	Unknown

Mondo (1): diarrhea 13 (MONDO:0957253)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001397	Hepatic steatosis
HP:0001508	Failure to thrive
HP:0001988	Recurrent hypoglycemia
HP:0002013	Vomiting
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003073	Hypoalbuminemia
HP:0003623	Neonatal onset
HP:0005208	Secretory diarrhea

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004599_10	Mean platelet volume	1.000000e-11
GCST004599_9	Mean platelet volume	1.000000e-24
GCST008949_1	High chromosomal aberration frequency (chromosome type) in genotoxic compound exposure	3.000000e-06
GCST010857_1	Amyotrophic lateral sclerosis	8.000000e-11
GCST90002380_97	Basophil percentage of white cells	7.000000e-12
GCST90002395_36	Mean platelet volume	2.000000e-11
GCST90002395_37	Mean platelet volume	3.000000e-18
GCST90002395_38	Mean platelet volume	6.000000e-26
GCST90002402_130	Platelet count	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009861	chromosome-type aberration frequency
EFO:0007992	basophil percentage of leukocytes
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105818 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,358 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL1088752	LOSMAPIMOD	3	865
CHEMBL491473	CEDIRANIB	3	9,098

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	Kd	8	nM	CEDIRANIB
6.68	Kd	208	nM	GILTERITINIB
5.77	Kd	1690	nM	LOSMAPIMOD

PubChem BioAssay actives

3 with measured affinity, of 181 total; 3 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-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	1424897: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0080	uM
Gilteritinib	1424897: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2080	uM
6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-N-(2,2-dimethylpropyl)pyridine-3-carboxamide	1424897: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.6900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	5
Acetaminophen	decreases expression, increases expression	4
Benzo(a)pyrene	affects expression, affects methylation, decreases expression	4
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	4
Cyclosporine	increases expression, decreases expression	3
GW 7647	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, decreases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	increases expression, decreases expression	2
Palmitic Acid	affects response to substance, affects abundance, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases expression, decreases response to substance	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	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
CHEMBL3991610	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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