ACSM2B

Summary

ACSM2B (acyl-CoA synthetase medium chain family member 2B, HGNC:30931) is a protein-coding gene on chromosome 16p12.3, encoding Acyl-coenzyme A synthetase ACSM2B, mitochondrial (Q68CK6). Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.

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

Source: NCBI Gene 348158 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_001105069

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30931
Approved symbol	ACSM2B
Name	acyl-CoA synthetase medium chain family member 2B
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	HXMA, HYST1046
Ensembl gene	ENSG00000066813
Ensembl biotype	protein_coding
OMIM	614359
Entrez	348158

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 26 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000329697, ENST00000414188, ENST00000562026, ENST00000563943, ENST00000564849, ENST00000564855, ENST00000565232, ENST00000565322, ENST00000566384, ENST00000566998, ENST00000567001, ENST00000567288, ENST00000568098, ENST00000568882, ENST00000569131, ENST00000569163, ENST00000569327, ENST00000569344, ENST00000569364, ENST00000879894, ENST00000879895, ENST00000879896, ENST00000879897, ENST00000879898, ENST00000879899, ENST00000879900, ENST00000879901, ENST00000879902, ENST00000879903, ENST00000879904, ENST00000879905, ENST00000879906, ENST00000879907, ENST00000879908

RefSeq mRNA: 3 — MANE Select: NM_001105069 NM_001105069, NM_001410902, NM_182617

CCDS: CCDS10586, CCDS92120

Canonical transcript exons

ENST00000329697 — 14 exons

Exon	Start	End
ENSE00001310510	20536226	20537362
ENSE00002615022	20576207	20576367
ENSE00003458323	20552144	20552297
ENSE00003479607	20555269	20555476
ENSE00003518477	20553777	20553920
ENSE00003568661	20546394	20546474
ENSE00003573990	20545157	20545258
ENSE00003577715	20540654	20540773
ENSE00003587428	20559237	20559447
ENSE00003595573	20548394	20548473
ENSE00003595576	20542914	20543013
ENSE00003632552	20564669	20564853
ENSE00003663612	20548062	20548185
ENSE00003674270	20543135	20543262

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 99.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0768 / max 35.1075, expressed in 12 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
207803	0.0464	11
156691	0.0159	5
156693	0.0103	6
156690	0.0035	3
156692	0.0007	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.47	gold quality
liver	UBERON:0002107	93.76	gold quality
adult mammalian kidney	UBERON:0000082	93.47	gold quality
kidney epithelium	UBERON:0004819	87.85	gold quality
kidney	UBERON:0002113	86.99	gold quality
cortex of kidney	UBERON:0001225	83.49	gold quality
metanephros cortex	UBERON:0010533	81.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.53	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.92	gold quality
colonic epithelium	UBERON:0000397	70.73	gold quality
metanephros	UBERON:0000081	67.32	gold quality
ileal mucosa	UBERON:0000331	59.22	silver quality
cerebellar vermis	UBERON:0004720	57.22	gold quality
sural nerve	UBERON:0015488	57.01	silver quality
left uterine tube	UBERON:0001303	56.21	gold quality
renal medulla	UBERON:0000362	55.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	55.24	gold quality
pancreatic ductal cell	CL:0002079	55.12	silver quality
right lobe of thyroid gland	UBERON:0001119	54.51	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	54.06	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
body of pancreas	UBERON:0001150	53.44	gold quality
tibialis anterior	UBERON:0001385	53.07	silver quality
adult organism	UBERON:0007023	52.21	silver quality
thyroid gland	UBERON:0002046	51.80	gold quality
left lobe of thyroid gland	UBERON:0001120	51.74	gold quality
deltoid	UBERON:0001476	51.73	gold quality
ectocervix	UBERON:0012249	50.76	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-135	yes	6352.91
E-CURD-119	yes	5671.67
E-GEOD-131882	yes	4752.80
E-HCAD-9	yes	55.35
E-HCAD-10	yes	30.24
E-ANND-3	yes	10.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting ACSM2B, 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-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-6867-3P	98.12	66.07	1305

Literature-anchored findings (GeneRIF, showing 2)

• results suggest an involvement of the medium-chain acyl-CoA synthetase 2 (MACS2) Leu513Ser polymorphism in the development of the metabolic syndrome in Caucasian population (PMID:16521160)
• This study assessed the naturally observed sequence diversity and protein expression variation of ACSM2A and ACSM2B. The allelic variation, haplotype diversity, Tajima’s D values, and phylogenetic analyses indicated that ACSM2A and ACSM2B are highly conserved.The protein expression analyses showed that ACSM2A is the predominant transcript in liver. (PMID:29948332)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acss2l	ENSDARG00000069029
mus_musculus	Acsm2	ENSMUSG00000030945
rattus_norvegicus	Acsm2	ENSRNOG00000064951
caenorhabditis_elegans		WBGENE00009221
caenorhabditis_elegans		WBGENE00018488

Paralogs (13): ACSM3 (ENSG00000005187), AACS (ENSG00000081760), ACSS3 (ENSG00000111058), ACSS2 (ENSG00000131069), ACSS1 (ENSG00000154930), AASDH (ENSG00000157426), ACSM1 (ENSG00000166743), ACSF2 (ENSG00000167107), ACSM6 (ENSG00000173124), ACSF3 (ENSG00000176715), ACSM5 (ENSG00000183549), ACSM2A (ENSG00000183747), ACSM4 (ENSG00000215009)

Protein

Protein identifiers

Acyl-coenzyme A synthetase ACSM2B, mitochondrial — Q68CK6 (reviewed: Q68CK6)

Alternative names: Acyl-CoA synthetase medium-chain family member 2B, Benzoate–CoA ligase, Butyrate–CoA ligase 2B, Butyryl-coenzyme A synthetase 2B, Middle-chain acyl-CoA synthetase 2B, Xenobiotic/medium-chain fatty acid-CoA ligase HXM-A

All UniProt accessions (9): Q68CK6, A0A087WU25, H3BM61, H3BNJ9, H3BP39, H3BP79, H3BQ84, H3BRR3, H3BTX9

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 (e.g. butyric (C4) to decanoic (C10) acids), and certain carboxylate-containing xenobiotics, e.g. benzoate.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion.

Tissue specificity. Detected in liver.

Activity regulation. Activated by monovalent cations, such as potassium, rubidium or ammonium.

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

RefSeq proteins (3): NP_001098539, NP_001397831, NP_872423 (=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), 6 shown:

• benzoate + ATP + CoA = benzoyl-CoA + AMP + diphosphate (RHEA:10132)
• 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)
• butanoate + ATP + CoA = butanoyl-CoA + AMP + diphosphate (RHEA:46172)
• a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate (RHEA:48340)

UniProt features (20 total): binding site 12, sequence conflict 5, transit peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68CK6-F1	91.41	0.84

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 (12): 501; 532; 540–542; 557; 139; 221–229; 359–364; 364; 446; 461; 469–471; 472

Post-translational modifications (1): 513

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-177128	Conjugation of salicylate with glycine
R-HSA-177135	Conjugation of benzoate with glycine
R-HSA-177162	Conjugation of phenylacetate with glutamine
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: 70 (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, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, chr16p12

GO Biological Process (5): fatty acid biosynthetic process (GO:0006633), acyl-CoA metabolic process (GO:0006637), xenobiotic metabolic process (GO:0006805), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (13): fatty-acyl-CoA synthase activity (GO:0004321), ATP binding (GO:0005524), fatty acid ligase activity (GO:0015645), CoA-ligase activity (GO:0016405), benzoate-CoA ligase activity (GO:0018858), metal ion binding (GO:0046872), decanoate-CoA ligase activity (GO:0102391), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874), ligase activity, forming carbon-sulfur bonds (GO:0016877), acid-thiol ligase activity (GO:0016878), medium-chain fatty acid-CoA ligase activity (GO:0031956)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Conjugation of carboxylic acids	3
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
metabolic process	1
cellular response to xenobiotic stimulus	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
CoA-ligase activity	1
cation binding	1
medium-chain fatty acid-CoA ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
ligase 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
cellular anatomical structure	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSM2B	GLYAT	Q6IB77	643
ACSM2B	AASDH	Q4L235	602
ACSM2B	IVD	P26440	396
ACSM2B	GLYATL1B	A0A0U1RQE8	389
ACSM2B	ACOT4	Q8N9L9	378
ACSM2B	HACL1	Q9UJ83	372
ACSM2B	SUOX	P51687	342
ACSM2B	ACOT9	Q9Y305	331
ACSM2B	HTD2	P86397	330
ACSM2B	ACOT12	Q8WYK0	326
ACSM2B	CRAT	P43155	326
ACSM2B	HAO2	Q9NYQ3	318
ACSM2B	DECR1	Q16698	309
ACSM2B	ACSL4	O60488	306
ACSM2B	ACSBG1	Q96GR2	303

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MAGEA11	ACSM2B	psi-mi:“MI:0915”(physical association)	0.560
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
ACSM2B	HSPA8	psi-mi:“MI:0914”(association)	0.350
ACSM2B	MAGEA11	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): MAGEA11 (Two-hybrid), ACSM2A (Affinity Capture-MS), HSPA8 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2351 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20540649:CTTA:C	donor_loss	1.0000
16:20540650:TTA:T	donor_loss	1.0000
16:20540651:TA:T	donor_loss	1.0000
16:20540652:A:AC	donor_gain	1.0000
16:20540652:A:AG	donor_loss	1.0000
16:20540653:C:CC	donor_gain	1.0000
16:20540653:CCTTT:C	donor_gain	1.0000
16:20540769:ACCAC:A	acceptor_gain	1.0000
16:20540770:CCAC:C	acceptor_gain	1.0000
16:20540770:CCACC:C	acceptor_gain	1.0000
16:20540771:CAC:C	acceptor_gain	1.0000
16:20540771:CACC:C	acceptor_gain	1.0000
16:20540772:AC:A	acceptor_gain	1.0000
16:20540773:CC:C	acceptor_gain	1.0000
16:20540774:C:CC	acceptor_gain	1.0000
16:20540781:A:C	acceptor_gain	1.0000
16:20540785:A:AC	acceptor_gain	1.0000
16:20540785:A:C	acceptor_gain	1.0000
16:20542904:T:TA	donor_gain	1.0000
16:20542905:C:A	donor_gain	1.0000
16:20542917:T:A	donor_gain	1.0000
16:20543134:CCCG:C	donor_gain	1.0000
16:20543186:T:C	donor_gain	1.0000
16:20543258:TTTTC:T	acceptor_gain	1.0000
16:20543259:TTTC:T	acceptor_gain	1.0000
16:20543260:TTC:T	acceptor_gain	1.0000
16:20543261:TC:T	acceptor_gain	1.0000
16:20543262:CC:C	acceptor_gain	1.0000
16:20543262:CCTG:C	acceptor_loss	1.0000
16:20543263:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000122845 (16:20552646 T>C), RS1000277553 (16:20547861 G>A), RS1000412809 (16:20543944 T>G), RS1000421353 (16:20577038 T>C), RS1000759195 (16:20542928 G>A), RS1000873528 (16:20565834 A>C,G), RS1000973698 (16:20560900 G>A), RS1001132999 (16:20556364 G>A,T), RS1001169730 (16:20575450 C>A), RS1001419040 (16:20556211 T>C), RS1001562271 (16:20568467 T>C), RS1001827265 (16:20558283 A>G), RS1002207006 (16:20572464 C>T), RS1002270515 (16:20540474 C>T), RS1002279678 (16:20567638 A>C,G)

Disease associations

OMIM: gene MIM:614359 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002388_9	Serum metabolite levels	6.000000e-11
GCST002592_29	Neuritic plaque	2.000000e-06
GCST009363_45	Triglyceride levels x short total sleep time interaction (2df test)	5.000000e-10
GCST009363_62	Triglyceride levels x short total sleep time interaction (2df test)	1.000000e-06
GCST010277_5	Gout	2.000000e-08
GCST012020_129	Serum metabolite levels	6.000000e-44
GCST012020_146	Serum metabolite levels	6.000000e-12
GCST012020_151	Serum metabolite levels	4.000000e-15
GCST012020_465	Serum metabolite levels	9.000000e-20
GCST012021_76	Serum metabolite levels	4.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement
EFO:0004530	triglyceride measurement

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
Benzo(a)pyrene	decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation	3
Valproic Acid	decreases expression, decreases methylation	2
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
benazol P	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Urethane	decreases expression	1
Palmitic Acid	decreases 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.