ACSM4

Summary

ACSM4 (acyl-CoA synthetase medium chain family member 4, HGNC:32016) is a protein-coding gene on chromosome 12p13.31, encoding Acyl-coenzyme A synthetase ACSM4, mitochondrial (P0C7M7). Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.

Predicted to enable decanoate-CoA 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 341392 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_001080454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32016
Approved symbol	ACSM4
Name	acyl-CoA synthetase medium chain family member 4
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000215009
Ensembl biotype	protein_coding
OMIM	614360
Entrez	341392

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000399422, ENST00000533292

RefSeq mRNA: 1 — MANE Select: NM_001080454 NM_001080454

CCDS: CCDS44825

Canonical transcript exons

ENST00000399422 — 13 exons

Exon	Start	End
ENSE00001538168	7328287	7328719
ENSE00001538171	7326976	7327095
ENSE00001538174	7324499	7324598
ENSE00001538183	7324273	7324400
ENSE00001538200	7323234	7323314
ENSE00001538205	7322418	7322541
ENSE00001538206	7320725	7320804
ENSE00001538210	7318026	7318182
ENSE00001538215	7310539	7310746
ENSE00001538217	7306533	7306743
ENSE00001538219	7304072	7304532
ENSE00001727634	7323459	7323560
ENSE00003505396	7317137	7317280

Expression profiles

Bgee: expression breadth broad, 82 present calls, max score 83.43.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.55	gold quality
right ovary	UBERON:0002118	60.62	gold quality
left ovary	UBERON:0002119	59.14	gold quality
ovary	UBERON:0000992	57.90	gold quality
rectum	UBERON:0001052	54.47	gold quality
spleen	UBERON:0002106	54.29	gold quality
cortical plate	UBERON:0005343	53.97	gold quality
stromal cell of endometrium	CL:0002255	53.56	gold quality
adrenal tissue	UBERON:0018303	52.19	gold quality
duodenum	UBERON:0002114	51.20	gold quality
gall bladder	UBERON:0002110	50.14	gold quality
right coronary artery	UBERON:0001625	49.90	gold quality
smooth muscle tissue	UBERON:0001135	49.25	gold quality
vermiform appendix	UBERON:0001154	49.25	gold quality
subcutaneous adipose tissue	UBERON:0002190	47.41	gold quality
adipose tissue	UBERON:0001013	46.07	gold quality
testis	UBERON:0000473	45.22	gold quality
mucosa of stomach	UBERON:0001199	45.00	gold quality
myometrium	UBERON:0001296	44.86	gold quality
mucosa of transverse colon	UBERON:0004991	44.23	silver quality
muscle tissue	UBERON:0002385	44.22	gold quality
omental fat pad	UBERON:0010414	44.22	gold quality
lymph node	UBERON:0000029	43.99	gold quality
monocyte	CL:0000576	43.59	silver quality
small intestine	UBERON:0002108	43.48	gold quality
superior frontal gyrus	UBERON:0002661	43.20	silver quality
left testis	UBERON:0004533	43.16	gold quality
sural nerve	UBERON:0015488	43.02	gold quality
endometrium	UBERON:0001295	42.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.23

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• SNPs associated with rapid AIDS progression (PMID:23982661)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acss2l	ENSDARG00000069029
mus_musculus	Acsm4	ENSMUSG00000047026
rattus_norvegicus	Acsm4	ENSRNOG00000014726
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), ACSM5 (ENSG00000183549), ACSM2A (ENSG00000183747)

Protein

Protein identifiers

Acyl-coenzyme A synthetase ACSM4, mitochondrial — P0C7M7 (reviewed: P0C7M7)

Alternative names: Acyl-CoA synthetase medium-chain family member 4

All UniProt accessions (1): P0C7M7

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. Capable of activating medium-chain fatty acids with a preference for C6-12 fatty acids.

Subcellular location. Mitochondrion.

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

RefSeq proteins (1): NP_001073923* (*=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), 5 shown:

• dodecanoate + ATP + CoA = dodecanoyl-CoA + AMP + diphosphate (RHEA:33623)
• decanoate + ATP + CoA = decanoyl-CoA + AMP + diphosphate (RHEA:33627)
• octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate (RHEA:33631)
• hexanoate + ATP + CoA = hexanoyl-CoA + AMP + diphosphate (RHEA:43740)
• a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate (RHEA:48340)

UniProt features (8 total): binding site 5, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C7M7-F1	89.38	0.77

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): 229–237; 368–373; 455; 470; 566

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: 42 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, 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, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_MATRIX, GOBP_FATTY_ACID_METABOLIC_PROCESS

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 (10): fatty-acyl-CoA synthase activity (GO:0004321), ATP binding (GO:0005524), fatty acid ligase activity (GO:0015645), metal ion binding (GO:0046872), decanoate-CoA ligase activity (GO:0102391), nucleotide binding (GO:0000166), CoA-ligase activity (GO:0016405), ligase activity (GO:0016874), acid-thiol ligase activity (GO:0016878), medium-chain fatty acid-CoA ligase activity (GO:0031956)

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
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
purine ribonucleoside triphosphate binding	1
ATP-dependent activity	1
cation binding	1
medium-chain fatty acid-CoA ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
ligase activity, forming carbon-sulfur bonds	1
fatty acid-CoA ligase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1563 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSM4	PRAMEF18	Q5VWM3	475
ACSM4	SPDYC	Q5MJ68	447
ACSM4	SAXO2	Q658L1	437
ACSM4	CYTL1	Q9NRR1	436
ACSM4	AASDH	Q4L235	428
ACSM4	BPIFB3	P59826	404
ACSM4	REG3G	Q6UW15	388
ACSM4	ECI2	O75521	388
ACSM4	ACSBG1	Q96GR2	373
ACSM4	ACOX2	Q99424	367
ACSM4	ACOT12	Q8WYK0	364
ACSM4	ACSL4	O60488	359
ACSM4	ACADL	P28330	352
ACSM4	ACSBG2	Q5FVE4	347
ACSM4	SUOX	P51687	342

IntAct

0 interactions, top by confidence:

BioGRID (3): ACSM4 (Synthetic Lethality), ACSM4 (Affinity Capture-MS), ACSM4 (Affinity Capture-RNA)

ESM2 similar proteins: A4IHY0, H9A1V3, M4IRL9, O70490, P0C7M7, P39062, Q08AH1, Q08AH3, Q0P4F7, Q17QJ1, Q3TMV7, Q3UNX5, Q3URE1, Q499N5, Q4G176, Q4R3Y4, Q4R4Z9, Q4R510, Q53FZ2, Q58DN7, Q5E9H9, Q5EA45, Q5I0K5, Q5R9G9, Q5RDY4, Q5REV5, Q5REX5, Q67Y55, Q68CK6, Q6AYT9, Q6GLK6, Q6P1M0, Q6P461, Q6PE15, Q6SKG1, Q7T0X7, Q7TN78, Q80W40, Q84P17, Q8K0L3

Diamond homologs: A0A0H2ZF83, A0A0H2ZGB9, A8NF97, A9W5V0, B7KPN8, G3J456, M4IQQ5, M4ISH2, O07899, O53521, O60011, P0C7M7, P10378, P38135, P39002, P40871, P71716, P80436, P86831, P86832, P9WEY3, P9WEZ0, Q01574, Q08AH1, Q08AH3, Q1IAK8, Q21LV0, Q2G512, Q2KHW5, Q53FZ2, Q5P603, Q5REV5, Q5SKN9, Q5ZKR7, Q68CK6, Q6SKG1, Q6ZAC1, Q7TYX8, Q7X279, Q84HC5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1846 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7313732:A:G	donor_gain	1.0000
12:7313737:G:GT	donor_gain	1.0000
12:7318180:GAC:G	donor_gain	1.0000
12:7322536:G:GT	donor_gain	1.0000
12:7326970:TTGCA:T	acceptor_loss	1.0000
12:7326971:TGCA:T	acceptor_loss	1.0000
12:7326972:GCAG:G	acceptor_loss	1.0000
12:7326973:CAGGT:C	acceptor_loss	1.0000
12:7326974:A:C	acceptor_loss	1.0000
12:7326975:G:GT	acceptor_loss	1.0000
12:7327116:T:G	donor_gain	1.0000
12:7313247:GACTT:G	donor_gain	0.9900
12:7313738:A:T	donor_gain	0.9900
12:7318183:G:GG	donor_gain	0.9900
12:7322536:G:T	donor_gain	0.9900
12:7324595:AGAG:A	donor_loss	0.9900
12:7324597:AGGT:A	donor_loss	0.9900
12:7324598:GG:G	donor_loss	0.9900
12:7324599:G:GA	donor_loss	0.9900
12:7324600:T:G	donor_loss	0.9900
12:7324622:G:GT	donor_gain	0.9900
12:7326969:GTTGC:G	acceptor_loss	0.9900
12:7326974:A:AG	acceptor_gain	0.9900
12:7326974:AG:A	acceptor_gain	0.9900
12:7326974:AGGT:A	acceptor_gain	0.9900
12:7326975:G:GG	acceptor_gain	0.9900
12:7326975:GG:G	acceptor_gain	0.9900
12:7326975:GGT:G	acceptor_gain	0.9900
12:7326975:GGTG:G	acceptor_gain	0.9900
12:7304528:AGAAG:A	donor_loss	0.9800

AlphaMissense

3804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7322488:T:A	W358R	0.988
12:7322488:T:C	W358R	0.988
12:7324552:T:A	V497D	0.986
12:7318060:T:A	W267R	0.984
12:7318060:T:C	W267R	0.984
12:7317204:A:C	S230R	0.983
12:7317206:T:A	S230R	0.983
12:7317206:T:G	S230R	0.983
12:7324534:T:A	L491H	0.983
12:7328335:C:A	R569S	0.983
12:7317198:T:C	F228L	0.982
12:7317200:C:A	F228L	0.982
12:7317200:C:G	F228L	0.982
12:7306635:G:C	A102P	0.981
12:7306713:T:A	W128R	0.981
12:7306713:T:C	W128R	0.981
12:7306738:G:C	R136P	0.980
12:7318117:T:A	W286R	0.980
12:7318117:T:C	W286R	0.980
12:7318081:T:A	W274R	0.979
12:7318081:T:C	W274R	0.979
12:7323286:G:A	G393E	0.979
12:7324327:G:C	D455H	0.979
12:7324534:T:C	L491P	0.979
12:7304490:C:A	N53K	0.978
12:7304490:C:G	N53K	0.978
12:7324567:T:A	V502D	0.978
12:7327088:C:A	P550Q	0.977
12:7328336:G:C	R569P	0.977
12:7310593:G:C	R156P	0.976

dbSNP variants (sampled 300 via entrez): RS1000017737 (12:7309187 G>A), RS1000182068 (12:7311680 TTTGTTG>T,TTTG,TTTGTTGTTG,TTTGTTGTTGTTG,TTTGTTGTTGTTGTTG), RS1000232864 (12:7312092 A>G), RS1000234356 (12:7311973 G>A,C), RS1000480216 (12:7306329 G>A,C), RS1000541518 (12:7304633 C>G), RS1000562306 (12:7310891 T>A,C,G), RS1000609809 (12:7306099 T>C), RS1000628311 (12:7303110 A>G), RS1000695065 (12:7304813 A>G), RS1000910045 (12:7324124 C>G), RS1000960363 (12:7323889 A>G,T), RS1001077501 (12:7317037 C>T), RS1001083068 (12:7303609 C>T), RS1001227108 (12:7304856 T>C)

Disease associations

OMIM: gene MIM:614360 | disease phenotypes: MIM:202370

GenCC curated gene-disease

Mondo (1): peroxisome biogenesis disorder 2B (MONDO:0008736)

Orphanet (1): Neonatal adrenoleukodystrophy (Orphanet:44)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_206	Refractive error	3.000000e-62

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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