ACSM6

Summary

ACSM6 (acyl-CoA synthetase medium chain family member 6, HGNC:31665) is a protein-coding gene on chromosome 10q23.33, encoding Acyl-coenzyme A synthetase ACSM6, mitochondrial (Q6P461). 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 142827 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 77 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_207321

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31665
Approved symbol	ACSM6
Name	acyl-CoA synthetase medium chain family member 6
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	bA310E22.3
Ensembl gene	ENSG00000173124
Ensembl biotype	protein_coding
Entrez	142827

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 nonsense_mediated_decay, 1 protein_coding

ENST00000327739, ENST00000394005, ENST00000404473

RefSeq mRNA: 1 — MANE Select: NM_207321 NM_207321

CCDS: CCDS7440

Canonical transcript exons

ENST00000394005 — 11 exons

Exon	Start	End
ENSE00001454805	95228644	95228929
ENSE00003476354	95210650	95210793
ENSE00003479035	95211878	95212034
ENSE00003485667	95207208	95207415
ENSE00003507543	95219891	95219971
ENSE00003518221	95212858	95212940
ENSE00003566241	95214852	95214975
ENSE00003593329	95201985	95202195
ENSE00003594260	95225290	95225391
ENSE00003661868	95194465	95194677
ENSE00003973392	95194238	95194303

Expression profiles

Bgee: expression breadth broad, 63 present calls, max score 78.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0268 / max 16.3130, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106351	0.0148	4
106350	0.0120	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	78.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.74	gold quality
cerebellar vermis	UBERON:0004720	76.03	gold quality
quadriceps femoris	UBERON:0001377	73.23	gold quality
body of pancreas	UBERON:0001150	68.34	gold quality
pancreas	UBERON:0001264	60.43	gold quality
sural nerve	UBERON:0015488	57.08	silver quality
body of stomach	UBERON:0001161	57.06	gold quality
stomach	UBERON:0000945	56.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	55.03	silver quality
adrenal tissue	UBERON:0018303	53.77	gold quality
right lobe of thyroid gland	UBERON:0001119	53.22	gold quality
fundus of stomach	UBERON:0001160	53.18	gold quality
bone marrow cell	CL:0002092	52.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.58	silver quality
skin of abdomen	UBERON:0001416	52.42	gold quality
thyroid gland	UBERON:0002046	52.24	gold quality
urinary bladder	UBERON:0001255	51.74	gold quality
bone marrow	UBERON:0002371	51.58	silver quality
left lobe of thyroid gland	UBERON:0001120	50.85	gold quality
zone of skin	UBERON:0000014	50.23	gold quality
corpus callosum	UBERON:0002336	49.63	silver quality
skin of leg	UBERON:0001511	48.66	gold quality
calcaneal tendon	UBERON:0003701	46.07	silver quality
islet of Langerhans	UBERON:0000006	45.30	gold quality
skeletal muscle tissue	UBERON:0001134	43.49	gold quality
colonic epithelium	UBERON:0000397	42.94	silver quality
cortex of kidney	UBERON:0001225	42.32	silver quality
kidney	UBERON:0002113	42.02	silver quality
lymph node	UBERON:0000029	41.24	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ACSM6, 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-4778-3P	99.93	70.40	1818
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-6761-3P	77.17	65.96	50

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	acss2l	ENSDARG00000069029
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), ACSF3 (ENSG00000176715), ACSM5 (ENSG00000183549), ACSM2A (ENSG00000183747), ACSM4 (ENSG00000215009)

Protein

Protein identifiers

Acyl-coenzyme A synthetase ACSM6, mitochondrial — Q6P461 (reviewed: Q6P461)

Alternative names: Acyl-CoA synthetase medium-chain family member 6

All UniProt accessions (3): Q6P461, H7BXS6, H7BYZ2

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.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q6P461-1	1	yes
Q6P461-2	2
Q6P461-3	3

RefSeq proteins (1): NP_997204* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000873	AMP-dep_synth/lig_dom	Domain
IPR042099	ANL_N_sf	Homologous_superfamily
IPR051087	Mitochondrial_ACSM	Family

Pfam: PF00501

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (13 total): binding site 4, splice variant 4, sequence variant 3, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P461-F1	84.04	0.66

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 (4): 226–234; 366–371; 453; 468

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-77352	Beta oxidation of butanoyl-CoA to acetyl-CoA
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-77286	mitochondrial fatty acid beta-oxidation of saturated fatty acids
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 44 (showing top): GCANCTGNY_MYOD_Q6, 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, REACTOME_MITOCHONDRIAL_FATTY_ACID_BETA_OXIDATION, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_MATRIX

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 (9): 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), ligase activity (GO:0016874), ligase activity, forming carbon-sulfur bonds (GO:0016877)

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

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
mitochondrial fatty acid beta-oxidation of saturated fatty acids	1
Metabolism	1
Mitochondrial Fatty Acid Beta-Oxidation	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleoside triphosphate binding	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
acid-thiol ligase activity	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
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1299 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSM6	OR10K2	Q6IF99	509
ACSM6	OR10T2	Q8NGX3	506
ACSM6	OR10K1	Q8NGX5	480
ACSM6	AASDH	Q4L235	442
ACSM6	MSLNL	Q96KJ4	400
ACSM6	CRAT	P43155	363
ACSM6	LIPJ	Q5W064	357
ACSM6	ACOXL	Q9NUZ1	355
ACSM6	OR7C1	O76099	348
ACSM6	PXMP2	Q9NR77	342
ACSM6	SUOX	P51687	342
ACSM6	HADHB	P55084	325
ACSM6	TLL2	Q9Y6L7	313
ACSM6	TM9SF3	Q9HD45	308
ACSM6	ACOX2	Q99424	302

IntAct

0 interactions, top by confidence:

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: A0A179HJB8, A4YDT1, A6NJU9, A8MRT5, C0SPB0, C9JG80, E5RHQ5, E9PIF3, E9PJ23, E9PQR5, F8W0I5, F8W1W9, O70490, P0C7M7, P39062, Q08AH1, Q08AH3, Q3UNX5, Q53FZ2, Q5REV5, Q68CK6, Q6AYT9, Q6NUN0, Q6P461, Q6SKG1, Q7TN78, Q80W40, Q8BGA8, Q8K0L3, Q91VA0, Q92617, Q9BEA2, A0R5G1, A4WJG1, B8FIN2, C1AA44, M4IQS1, O06417, O93730, P31686

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	3
Likely pathogenic	1
Uncertain significance	64
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
148854	GRCh38/hg38 10q23.33-24.1(chr10:92643919-95471137)x1	Pathogenic
1527596	GRCh37/hg19 10q23.31-24.1(chr10:92667881-98970384)	Pathogenic
3063132	GRCh37/hg19 10q23.31-24.2(chr10:90796994-100067505)x1	Pathogenic
625558	GRCh37/hg19 10q23.33-24.1(chr10:94393383-97219175)	Likely pathogenic

SpliceAI

1472 predictions. Top by Δscore:

Variant	Effect	Δscore
10:95207373:A:G	donor_gain	1.0000
10:95207416:G:GG	donor_gain	1.0000
10:95210640:T:TA	acceptor_gain	1.0000
10:95210649:GA:G	acceptor_gain	1.0000
10:95195766:G:GG	donor_gain	0.9900
10:95207207:GGA:G	acceptor_gain	0.9900
10:95207380:C:G	donor_gain	0.9900
10:95207391:G:GA	donor_gain	0.9900
10:95207404:G:GT	donor_gain	0.9900
10:95207412:TTCA:T	donor_gain	0.9900
10:95207413:TCAGT:T	donor_loss	0.9900
10:95207415:AGTAA:A	donor_loss	0.9900
10:95207416:G:T	donor_loss	0.9900
10:95207417:TA:T	donor_loss	0.9900
10:95207418:AA:A	donor_loss	0.9900
10:95210641:G:A	acceptor_gain	0.9900
10:95210644:TTACA:T	acceptor_loss	0.9900
10:95210645:TACA:T	acceptor_loss	0.9900
10:95210647:CAGAG:C	acceptor_loss	0.9900
10:95210648:A:AG	acceptor_gain	0.9900
10:95210648:A:AT	acceptor_loss	0.9900
10:95210649:G:GG	acceptor_gain	0.9900
10:95210649:G:GT	acceptor_loss	0.9900
10:95210758:G:GG	donor_gain	0.9900
10:95211972:TTCC:T	donor_gain	0.9900
10:95211979:GAGCC:G	donor_gain	0.9900
10:95212035:G:GG	donor_gain	0.9900
10:95212848:T:A	acceptor_gain	0.9900
10:95212849:G:A	acceptor_gain	0.9900
10:95214976:G:GG	donor_gain	0.9900

AlphaMissense

3146 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:95202054:T:C	F88L	0.958
10:95202056:T:A	F88L	0.958
10:95202056:T:G	F88L	0.958
10:95211969:T:A	W283R	0.958
10:95211969:T:C	W283R	0.958
10:95202185:T:G	C131W	0.956
10:95194636:T:C	F51L	0.943
10:95194638:T:A	F51L	0.943
10:95194638:T:G	F51L	0.943
10:95202183:T:C	C131R	0.941
10:95207390:T:A	W196R	0.940
10:95207390:T:C	W196R	0.940
10:95211990:T:C	F290L	0.938
10:95211992:T:A	F290L	0.938
10:95211992:T:G	F290L	0.938
10:95214922:T:A	W356R	0.938
10:95214922:T:C	W356R	0.938
10:95212870:T:C	F309L	0.937
10:95212872:T:A	F309L	0.937
10:95212872:T:G	F309L	0.937
10:95194630:T:C	F49L	0.931
10:95194632:T:A	F49L	0.931
10:95194632:T:G	F49L	0.931
10:95202184:G:A	C131Y	0.930
10:95219942:G:T	G391W	0.926
10:95219943:G:T	G391V	0.926
10:95219943:G:A	G391E	0.925
10:95211912:T:A	W264R	0.923
10:95211912:T:C	W264R	0.923
10:95214924:G:C	W356C	0.919

dbSNP variants (sampled 300 via entrez): RS1000095820 (10:95228735 G>A), RS1000172644 (10:95201335 G>A), RS1000242896 (10:95223465 A>G,T), RS1000275073 (10:95208705 T>C,G), RS1000299014 (10:95228418 C>T), RS1000308251 (10:95195426 A>G), RS1000338299 (10:95195556 T>C), RS1000346908 (10:95215774 G>A), RS1000522151 (10:95208385 T>C), RS1000529961 (10:95228952 A>G), RS1000585949 (10:95207753 C>A,T), RS1000657656 (10:95199551 A>G), RS1000712591 (10:95200999 T>C), RS1000715248 (10:95200661 C>G,T), RS1000809808 (10:95200467 T>C)

Disease associations

OMIM: gene `` | 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
GCST009733_129	Urinary metabolite levels in chronic kidney disease	1.000000e-12
GCST011346_61	Total cholesterol levels	8.000000e-09
GCST011347_37	Low density lipoprotein cholesterol levels	2.000000e-08
GCST011742_31	Triglyceride levels in HIV infection	8.000000e-06
GCST012020_580	Serum metabolite levels	1.000000e-10
GCST012021_97	Serum metabolite levels	1.000000e-10
GCST012490_633	Femur bone mineral density x serum urate levels interaction	3.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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