ACSM5

Summary

ACSM5 (acyl-CoA synthetase medium chain family member 5, HGNC:26060) is a protein-coding gene on chromosome 16p12.3, encoding Acyl-coenzyme A synthetase ACSM5, mitochondrial (Q6NUN0). Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.

Predicted to enable fatty acid ligase activity and fatty-acyl-CoA synthase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion.

Source: NCBI Gene 54988 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_017888

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26060
Approved symbol	ACSM5
Name	acyl-CoA synthetase medium chain family member 5
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20581
Ensembl gene	ENSG00000183549
Ensembl biotype	protein_coding
OMIM	614361
Entrez	54988

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000331849, ENST00000570305, ENST00000573920, ENST00000574748, ENST00000575070, ENST00000575584, ENST00000577024, ENST00000909250, ENST00000909251, ENST00000909252, ENST00000909253, ENST00000909254, ENST00000909255, ENST00000909256, ENST00000909257, ENST00000909258, ENST00000909259, ENST00000909260, ENST00000909261, ENST00000909262, ENST00000909263, ENST00000909264

RefSeq mRNA: 4 — MANE Select: NM_017888 NM_001324371, NM_001324372, NM_001324373, NM_017888

CCDS: CCDS10585, CCDS81954

Canonical transcript exons

ENST00000331849 — 14 exons

Exon	Start	End
ENSE00001289956	20411470	20411688
ENSE00001297544	20437052	20437179
ENSE00001300905	20421258	20421401
ENSE00001305492	20430993	20431073
ENSE00001307721	20418059	20418269
ENSE00001311255	20437268	20437367
ENSE00001326346	20419228	20419435
ENSE00001330992	20409534	20409665
ENSE00001377752	20440344	20441336
ENSE00003475105	20439800	20439919
ENSE00003539823	20427788	20427867
ENSE00003547451	20429678	20429801
ENSE00003566184	20431220	20431321
ENSE00003689573	20423916	20424069

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 98.02.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0786 / max 225.1722, expressed in 266 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153055	0.4402	148
153056	0.3412	124
153057	0.2972	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.02	gold quality
liver	UBERON:0002107	95.99	gold quality
buccal mucosa cell	CL:0002336	92.99	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.72	gold quality
gluteal muscle	UBERON:0002000	85.44	gold quality
gastrocnemius	UBERON:0001388	84.75	gold quality
adipose tissue	UBERON:0001013	84.53	gold quality
muscle of leg	UBERON:0001383	84.31	gold quality
adult mammalian kidney	UBERON:0000082	84.02	gold quality
connective tissue	UBERON:0002384	83.25	gold quality
triceps brachii	UBERON:0001509	82.38	silver quality
muscle organ	UBERON:0001630	82.19	gold quality
nephron tubule	UBERON:0001231	81.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.47	gold quality
omental fat pad	UBERON:0010414	81.17	gold quality
peritoneum	UBERON:0002358	81.09	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.58	gold quality
kidney	UBERON:0002113	78.48	gold quality
tibial nerve	UBERON:0001323	78.26	gold quality
kidney epithelium	UBERON:0004819	78.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.87	gold quality
caput epididymis	UBERON:0004358	77.81	gold quality
biceps brachii	UBERON:0001507	77.77	gold quality
spinal cord	UBERON:0002240	76.94	gold quality
quadriceps femoris	UBERON:0001377	76.80	silver quality
substantia nigra	UBERON:0002038	76.69	gold quality
vastus lateralis	UBERON:0001379	76.62	silver quality
hindlimb stylopod muscle	UBERON:0004252	76.60	gold quality
cortex of kidney	UBERON:0001225	76.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.55
E-ENAD-17	no	171.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ACSM5, 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-544A	99.84	68.66	1965
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-1911-5P	98.92	67.53	325
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-610	96.84	67.98	905
HSA-MIR-4509	96.19	65.80	900
HSA-MIR-3918	96.13	64.65	1300

Literature-anchored findings (GeneRIF, showing 2)

• Integrative analysis of genome-wide DNA methylation and single-nucleotide polymorphism identified ACSM5 as a suppressor of lumbar ligamentum flavum hypertrophy. (PMID:34593020)
• Acyl-CoA Synthetase Medium-Chain Family Member 5-Mediated Fatty Acid Metabolism Dysregulation Promotes the Progression of Hepatocellular Carcinoma. (PMID:39069168)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acss2l	ENSDARG00000069029
mus_musculus	Acsm5	ENSMUSG00000030972
rattus_norvegicus	Acsm5	ENSRNOG00000031211
caenorhabditis_elegans		WBGENE00009221
caenorhabditis_elegans		WBGENE00018488

Paralogs (13): ACSM3 (ENSG00000005187), ACSM2B (ENSG00000066813), AACS (ENSG00000081760), ACSS3 (ENSG00000111058), ACSS2 (ENSG00000131069), ACSS1 (ENSG00000154930), AASDH (ENSG00000157426), ACSM1 (ENSG00000166743), ACSF2 (ENSG00000167107), ACSM6 (ENSG00000173124), ACSF3 (ENSG00000176715), ACSM2A (ENSG00000183747), ACSM4 (ENSG00000215009)

Protein

Protein identifiers

Acyl-coenzyme A synthetase ACSM5, mitochondrial — Q6NUN0 (reviewed: Q6NUN0)

Alternative names: Acyl-CoA synthetase medium-chain family member 5

All UniProt accessions (3): A0A087WTR4, Q6NUN0, I3L536

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Detected in kidney and liver.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6NUN0-1	1	yes
Q6NUN0-2	2

RefSeq proteins (4): NP_001311300, NP_001311301, NP_001311302, NP_060358* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000873	AMP-dep_synth/lig_dom	Domain
IPR020845	AMP-binding_CS	Conserved_site
IPR025110	AMP-bd_C	Domain
IPR042099	ANL_N_sf	Homologous_superfamily
IPR045851	AMP-b_sf	Homologous_superfamily
IPR051087	Mitochondrial_ACSM	Family

Pfam: PF00501, PF13193

Catalyzed reactions (Rhea), 1 shown:

• a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate (RHEA:48340)

UniProt features (23 total): sequence variant 7, modified residue 5, binding site 5, sequence conflict 3, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUN0-F1	90.58	0.74

Functional residue map

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

Ligand- & substrate-binding residues (5): 230–238; 368–373; 455; 470; 566

Post-translational modifications (5): 303, 303, 97, 97, 152

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-177128	Conjugation of salicylate with glycine
R-HSA-9749641	Aspirin ADME
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-156587	Amino Acid conjugation
R-HSA-159424	Conjugation of carboxylic acids
R-HSA-211859	Biological oxidations
R-HSA-9748784	Drug ADME

MSigDB gene sets: 103 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, MODULE_255, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_FATTY_ACID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, ACEVEDO_LIVER_CANCER_UP

GO Biological Process (4): fatty acid biosynthetic process (GO:0006633), acyl-CoA metabolic process (GO:0006637), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (11): fatty-acyl-CoA synthase activity (GO:0004321), ATP binding (GO:0005524), GTP binding (GO:0005525), fatty acid ligase activity (GO:0015645), medium-chain fatty acid-CoA ligase activity (GO:0031956), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), CoA-ligase activity (GO:0016405), ligase activity (GO:0016874), ligase activity, forming carbon-sulfur bonds (GO:0016877), acid-thiol ligase activity (GO:0016878)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Conjugation of carboxylic acids	1
Drug ADME	1
Biological oxidations	1
Phase II - Conjugation of compounds	1
Amino Acid conjugation	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleoside triphosphate binding	2
acid-thiol ligase activity	2
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1
ATP-dependent activity	1
fatty acid-CoA ligase activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
ligase activity	1
ligase activity, forming carbon-sulfur bonds	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSM5	AASDH	Q4L235	442
ACSM5	ZNF888	P0CJ79	419
ACSM5	HAO2	Q9NYQ3	416
ACSM5	PLA2G12A	Q9BZM1	384
ACSM5	CROT	Q9UKG9	347
ACSM5	SUOX	P51687	342
ACSM5	ELOVL6	Q9H5J4	339
ACSM5	OR8G1	Q15617	323
ACSM5	STK32B	Q9NY57	315
ACSM5	ACOT4	Q8N9L9	310
ACSM5	PEX2	P28328	310
ACSM5	CRAT	P43155	302
ACSM5	HACL1	Q9UJ83	299
ACSM5	CIBAR2	Q6ZTR7	299
ACSM5	ACADL	P28330	293

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ACSM5	AHNAK	psi-mi:“MI:0915”(physical association)	0.400
EP300	ACSM5	psi-mi:“MI:0915”(physical association)	0.370
ACSM5	CLUH	psi-mi:“MI:0914”(association)	0.350
ACSM5	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): ACSF2 (Affinity Capture-MS), PDPR (Affinity Capture-MS), POLG (Affinity Capture-MS), NARS2 (Affinity Capture-MS), FDXR (Affinity Capture-MS), PCCA (Affinity Capture-MS), LARS2 (Affinity Capture-MS), CPS1 (Affinity Capture-MS), NUDT19 (Affinity Capture-MS), MCCC1 (Affinity Capture-MS), PPOX (Affinity Capture-MS), CLUH (Affinity Capture-MS), UBR4 (Affinity Capture-MS), IARS2 (Affinity Capture-MS), ACSM5 (Proximity Label-MS)

ESM2 similar proteins: A2AIG8, A6NKP2, E9PTA2, O00764, O14734, O15315, O35331, O35719, O43502, O54783, O55229, O94759, P33124, P58137, Q3SWX2, Q3U129, Q4PS77, Q5I0K3, Q5RE34, Q5RJZ1, Q5T1C6, Q5ZM83, Q6AYT9, Q6DC64, Q6GV29, Q6NUN0, Q8BGA8, Q8CIW5, Q8IZ69, Q8K183, Q8K297, Q8N0X4, Q8R2J9, Q8R4N0, Q8TCT0, Q8VCE6, Q8VHK0, Q8VHQ9, Q8WXI4, Q91WC3

Diamond homologs: A0B8F1, A0KNI2, A0KY83, A0L576, A0R5G1, A1JIK3, A1RIK1, A1SZA2, A1WY97, A3D3E8, A3QD52, A4SJM6, A4TS06, A4WJG1, A4Y7Y7, A4YDT1, A4YGR1, A6UED8, A6WM52, A6WXV8, A7FNG1, A7HSR8, A7MPJ7, A8AN29, A8FUF1, A8G8G7, A8H5P1, A8PDE3, A9KY56, B0S8X7, B0SRX5, B0TPY4, B1M0M1, B2S7N5, B8FIN2, C0SPB0, C1AA44, O13440, O70490, O93730

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1939 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20411461:T:TA	acceptor_gain	1.0000
16:20418154:G:GT	donor_gain	1.0000
16:20421255:CAGGG:C	acceptor_gain	1.0000
16:20421256:AG:A	acceptor_gain	1.0000
16:20421256:AGGGA:A	acceptor_gain	1.0000
16:20421257:GG:G	acceptor_gain	1.0000
16:20421257:GGGA:G	acceptor_gain	1.0000
16:20421257:GGGAG:G	acceptor_gain	1.0000
16:20421372:C:G	donor_gain	1.0000
16:20421399:A:T	donor_gain	1.0000
16:20421445:G:T	donor_gain	1.0000
16:20424066:GAAT:G	donor_gain	1.0000
16:20424070:G:GG	donor_gain	1.0000
16:20429666:T:A	acceptor_gain	1.0000
16:20429670:T:TA	acceptor_gain	1.0000
16:20429798:AACGG:A	donor_loss	1.0000
16:20429800:CGG:C	donor_loss	1.0000
16:20429802:G:GA	donor_loss	1.0000
16:20429803:T:A	donor_loss	1.0000
16:20431214:TACCA:T	acceptor_loss	1.0000
16:20431215:ACCAG:A	acceptor_loss	1.0000
16:20431216:CCAGA:C	acceptor_loss	1.0000
16:20431218:A:AG	acceptor_gain	1.0000
16:20431218:AGA:A	acceptor_loss	1.0000
16:20431219:G:GC	acceptor_loss	1.0000
16:20431219:G:GG	acceptor_gain	1.0000
16:20431219:GATT:G	acceptor_gain	1.0000
16:20431319:TTGG:T	donor_loss	1.0000
16:20431320:TGGTA:T	donor_loss	1.0000
16:20431321:GGT:G	donor_loss	1.0000

AlphaMissense

3771 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20423971:T:A	W275R	0.995
16:20423971:T:C	W275R	0.995
16:20421325:A:C	S231R	0.994
16:20421327:C:A	S231R	0.994
16:20421327:C:G	S231R	0.994
16:20423950:T:A	W268R	0.993
16:20423950:T:C	W268R	0.993
16:20437321:T:A	V497D	0.991
16:20421319:T:C	F229L	0.989
16:20421321:T:A	F229L	0.989
16:20421321:T:G	F229L	0.989
16:20423973:G:C	W275C	0.989
16:20423973:G:T	W275C	0.989
16:20429748:T:A	W358R	0.989
16:20429748:T:C	W358R	0.989
16:20439912:C:A	P550H	0.988
16:20424004:T:A	W286R	0.987
16:20424004:T:C	W286R	0.987
16:20439907:A:C	K548N	0.987
16:20439907:A:T	K548N	0.987
16:20429797:A:T	E374V	0.986
16:20439870:T:C	L536P	0.985
16:20419282:G:C	R157P	0.984
16:20437152:G:C	R470T	0.984
16:20437303:T:C	L491P	0.984
16:20440402:T:C	L572S	0.983
16:20437153:A:C	R470S	0.982
16:20437153:A:T	R470S	0.982
16:20439810:C:A	A516E	0.982
16:20423969:G:A	G274D	0.981

dbSNP variants (sampled 300 via entrez): RS1000014215 (16:20438716 G>A,C), RS1000078446 (16:20411833 T>A,C), RS1000128255 (16:20439076 C>T), RS1000166268 (16:20420094 A>G), RS1000412481 (16:20408540 A>G), RS1000457556 (16:20414755 C>T), RS1000482766 (16:20433589 AAG>A), RS1000680634 (16:20412950 T>A), RS1000681808 (16:20420300 T>A), RS1000728324 (16:20419378 A>C), RS1000997059 (16:20428571 G>A), RS1001113620 (16:20423804 T>C), RS1001212190 (16:20426218 A>G,T), RS1001381271 (16:20434219 T>C), RS1001490360 (16:20436487 C>G)

Disease associations

OMIM: gene MIM:614361 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000649_18	Chronic kidney disease	1.000000e-20

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
Aflatoxin B1	affects expression, decreases expression	3
Acetaminophen	decreases expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
bisphenol S	increases expression	1
Rosiglitazone	decreases expression	1
Estradiol	decreases expression	1
Folic Acid	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	decreases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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