ACOT12

Summary

ACOT12 (acyl-CoA thioesterase 12, HGNC:24436) is a protein-coding gene on chromosome 5q14.1, encoding Acetyl-coenzyme A thioesterase (Q8WYK0). Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels.

Enables identical protein binding activity. Predicted to be involved in acetyl-CoA metabolic process. Located in cytosol; intercellular bridge; and nucleoplasm.

Source: NCBI Gene 134526 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 114 total — 1 pathogenic
• MANE Select transcript: NM_130767

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24436
Approved symbol	ACOT12
Name	acyl-CoA thioesterase 12
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	Cach, THEAL, STARD15
Ensembl gene	ENSG00000172497
Ensembl biotype	protein_coding
OMIM	614315
Entrez	134526

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000307624, ENST00000506440, ENST00000508234, ENST00000513751, ENST00000905739, ENST00000905740

RefSeq mRNA: 1 — MANE Select: NM_130767 NM_130767

CCDS: CCDS4055

Canonical transcript exons

ENST00000307624 — 15 exons

Exon	Start	End
ENSE00001120332	81329996	81330543
ENSE00001162960	81342672	81342755
ENSE00001162972	81344160	81344215
ENSE00001162977	81344891	81345041
ENSE00001162980	81345885	81346004
ENSE00001162986	81347774	81347930
ENSE00001162995	81359903	81360038
ENSE00001163003	81363788	81363889
ENSE00001163010	81371750	81371810
ENSE00001163018	81385757	81385826
ENSE00001242042	81393988	81394134
ENSE00003462734	81332477	81332605
ENSE00003514168	81335768	81335901
ENSE00003537423	81330814	81330940
ENSE00003596565	81343818	81343881

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 94.20.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1014 / max 35.4914, expressed in 12 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62320	0.0870	11
62321	0.0144	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	94.20	gold quality
liver	UBERON:0002107	92.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.22	gold quality
buccal mucosa cell	CL:0002336	67.89	silver quality
adult mammalian kidney	UBERON:0000082	61.32	gold quality
metanephros cortex	UBERON:0010533	58.55	gold quality
kidney	UBERON:0002113	56.84	gold quality
tibialis anterior	UBERON:0001385	56.46	silver quality
ileal mucosa	UBERON:0000331	55.75	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.90	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
metanephros	UBERON:0000081	53.57	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.17	gold quality
duodenum	UBERON:0002114	52.80	gold quality
cortex of kidney	UBERON:0001225	52.66	gold quality
lower lobe of lung	UBERON:0008949	52.59	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.47	silver quality
myocardium	UBERON:0002349	50.49	gold quality
deltoid	UBERON:0001476	50.46	silver quality
calcaneal tendon	UBERON:0003701	50.03	gold quality
cerebellar vermis	UBERON:0004720	48.63	gold quality
pancreatic ductal cell	CL:0002079	47.82	silver quality
stromal cell of endometrium	CL:0002255	47.30	gold quality
quadriceps femoris	UBERON:0001377	47.19	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
small intestine	UBERON:0002108	46.92	gold quality
hypothalamus	UBERON:0001898	46.24	gold quality
tendon	UBERON:0000043	46.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting ACOT12, 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-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-4774-5P	95.92	68.27	827

Literature-anchored findings (GeneRIF, showing 6)

• The human CACH cDNA encodes a 555-amino-acid sequence that is 81.4%/78.7% identical to those of the mouse/rat homologue, suggesting a conserved role for this enzyme in the human and rodent livers. (PMID:16951743)
• using a range of structural and biophysical techniques, it is demonstrated that ACOT12 is a trimer rather than a tetramer and that neither ADP nor ATP exert their regulatory effects by altering the oligomeric status of the enzyme (PMID:25002576)
• The ACOT12 could be a prognostic marker and a potential therapeutic target for combating hepatocellular carcinoma (HCC) metastasis. (PMID:30661930)
• Variation at ACOT12 and CT62 locus represents susceptibility to psoriasis in Han population. (PMID:31858748)
• Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue. (PMID:34285335)
• Exosomal miR-155-5p derived from glioma stem-like cells promotes mesenchymal transition via targeting ACOT12. (PMID:35986010)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	acot12	ENSDARG00000054534
mus_musculus	Acot12	ENSMUSG00000021620
rattus_norvegicus	Acot12	ENSRNOG00000061414

Paralogs (2): ACOT7 (ENSG00000097021), ACOT11 (ENSG00000162390)

Protein

Protein identifiers

Acetyl-coenzyme A thioesterase — Q8WYK0 (reviewed: Q8WYK0)

Alternative names: Acyl-CoA thioester hydrolase 12, Acyl-coenzyme A thioesterase 12, Cytoplasmic acetyl-CoA hydrolase 1, START domain-containing protein 15

All UniProt accessions (1): Q8WYK0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. Preferentially hydrolyzes acetyl-CoA.

Subunit / interactions. Homodimer or homotetramer.

Subcellular location. Cytoplasm. Cytosol.

Activity regulation. Inhibited by ADP. Active in the presence of ATP. Cold labile, it dissociates into inactive monomers at low temperature.

Pathway. Lipid metabolism; fatty acid metabolism.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WYK0-1	1	yes
Q8WYK0-2	2

RefSeq proteins (1): NP_570123* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002913	START_lipid-bd_dom	Domain
IPR006683	Thioestr_dom	Domain
IPR023393	START-like_dom_sf	Homologous_superfamily
IPR029069	HotDog_dom_sf	Homologous_superfamily
IPR033120	HOTDOG_ACOT	Domain
IPR040170	Cytosol_ACT	Family

Pfam: PF01852, PF03061

Enzyme classification (BRENDA):

• EC 3.1.2.1 — acetyl-CoA hydrolase (BRENDA: 33 organisms, 27 substrates, 33 inhibitors, 16 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0001–15	14
ACETOACETYL-COA	0.33	1
BUTYRYL-COA	0.41	1

Catalyzed reactions (Rhea), 3 shown:

• acetyl-CoA + H2O = acetate + CoA + H(+) (RHEA:20289)
• butanoyl-CoA + H2O = butanoate + CoA + H(+) (RHEA:40111)
• hexanoyl-CoA + H2O = hexanoate + CoA + H(+) (RHEA:40115)

UniProt features (40 total): strand 14, helix 9, binding site 4, domain 3, modified residue 3, sequence variant 3, splice variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4MOB	X-RAY DIFFRACTION	2.4
4MOC	X-RAY DIFFRACTION	2.5
3B7K	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYK0-F1	88.21	0.62

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): 53–55; 82–84; 144; 234–236

Post-translational modifications (3): 228, 33, 159

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 60 (showing top): GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, REACTOME_MITOCHONDRIAL_FATTY_ACID_BETA_OXIDATION, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_FATTY_ACID_METABOLIC_PROCESS, GOMF_ACYL_COA_HYDROLASE_ACTIVITY, GOMF_THIOLESTER_HYDROLASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, GOMF_LIPID_BINDING

GO Biological Process (4): acetyl-CoA metabolic process (GO:0006084), fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), lipid metabolic process (GO:0006629)

GO Molecular Function (8): acetyl-CoA hydrolase activity (GO:0003986), ATP binding (GO:0005524), lipid binding (GO:0008289), identical protein binding (GO:0042802), carboxylic ester hydrolase activity (GO:0052689), protein binding (GO:0005515), hydrolase activity (GO:0016787), thiolester hydrolase activity (GO:0016790)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), intercellular bridge (GO:0045171)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
hydrolase activity, acting on ester bonds	2
acyl-CoA metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
primary metabolic process	1
acyl-CoA hydrolase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACOT12	ACOT8	O14734	656
ACOT12	ACSS2	Q9NR19	608
ACOT12	ACSS1	Q9NUB1	576
ACOT12	ACOT13	Q9NPJ3	570
ACOT12	PCTP	Q9UKL6	566
ACOT12	ACOT9	Q9Y305	563
ACOT12	ACOT6	Q3I5F7	552
ACOT12	STARD5	P59094	519
ACOT12	STARD6	P59095	506
ACOT12	STAR	P49675	505
ACOT12	STARD7	Q9NQZ5	476
ACOT12	STARD10	Q9Y365	476
ACOT12	CRAT	P43155	475
ACOT12	STARD3	Q14849	446
ACOT12	ACOT2	P49753	427

IntAct

33 interactions, top by confidence:

A	B	Type	Score
ACOT12	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.740
PAX5	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
MEOX1	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
ACOT12	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
NAA10	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
REL	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
ACOT7	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
ACOT12	NAA11	psi-mi:“MI:0915”(physical association)	0.560
PAX6	ACOT12	psi-mi:“MI:0915”(physical association)	0.560
ACOT12	INPPL1	psi-mi:“MI:0914”(association)	0.530
ACOT12	PAX5	psi-mi:“MI:0915”(physical association)	0.000
ACOT12	MEOX1	psi-mi:“MI:0915”(physical association)	0.000
ACOT12	ACOT12	psi-mi:“MI:0915”(physical association)	0.000
ACOT12	PAX6	psi-mi:“MI:0915”(physical association)	0.000
ACOT12	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
ACOT12	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.000
NAA10	ACOT12	psi-mi:“MI:0915”(physical association)	0.000
ACOT12	REL	psi-mi:“MI:0915”(physical association)	0.000
ACOT7	ACOT12	psi-mi:“MI:0915”(physical association)	0.000
NAA11	ACOT12	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): ZBTB8A (Affinity Capture-MS), ACOT11 (Affinity Capture-MS), INPPL1 (Affinity Capture-MS), TLR5 (Affinity Capture-MS), SPAG9 (Affinity Capture-MS), ZMYM6 (Affinity Capture-MS), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid), ACOT12 (Two-hybrid)

ESM2 similar proteins: A1A4M6, A5GFX0, A5PJU6, O46689, O88736, P49675, P51557, P53808, P59095, P59096, P70114, P79245, P97826, Q28918, Q28996, Q3U1V6, Q4R5S9, Q58DB0, Q5BKH5, Q5IH13, Q5IH14, Q5R8P9, Q64421, Q6GM21, Q6IQS6, Q6NTS7, Q6P9U4, Q6TMK8, Q8R1R3, Q8VE85, Q8WYK0, Q90673, Q90ZB9, Q94E75, Q96DR4, Q96N28, Q99JV5, Q99NB7, Q9CYY7, Q9DBK0

Diamond homologs: O00154, O66120, O84540, P0A0Q7, P0A0Q8, P0A1A1, P0A1A2, P0A8Z0, P0A8Z1, P0A8Z2, P44886, P49851, Q64559, Q89AL4, Q8VHQ9, Q8WXI4, Q8WYK0, Q91V12, Q99NB7, Q9DBK0, Q9PJK7, Q9Z7Q0, S4TF94, Q6ZUV0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	101
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58096	GRCh38/hg38 5q13.3-22.1(chr5:74163186-110809453)x3	Pathogenic

SpliceAI

2821 predictions. Top by Δscore:

Variant	Effect	Δscore
5:81332475:AC:A	donor_gain	1.0000
5:81332476:CC:C	donor_gain	1.0000
5:81332476:CCCAT:C	donor_gain	1.0000
5:81345878:A:AC	donor_gain	1.0000
5:81345879:C:CC	donor_gain	1.0000
5:81359897:A:AC	donor_gain	1.0000
5:81359898:C:CC	donor_gain	1.0000
5:81359920:T:A	donor_gain	1.0000
5:81359966:T:A	donor_gain	1.0000
5:81360034:TGAAT:T	acceptor_gain	1.0000
5:81360039:C:CC	acceptor_gain	1.0000
5:81369082:T:C	acceptor_gain	1.0000
5:81371809:CT:C	acceptor_gain	1.0000
5:81385756:CCTAG:C	donor_gain	1.0000
5:81393983:CCTA:C	donor_loss	1.0000
5:81393984:CTA:C	donor_loss	1.0000
5:81393985:TAC:T	donor_loss	1.0000
5:81393986:A:AC	donor_gain	1.0000
5:81393986:AC:A	donor_gain	1.0000
5:81393986:ACCCG:A	donor_gain	1.0000
5:81393987:C:CC	donor_gain	1.0000
5:81393987:CC:C	donor_gain	1.0000
5:81393987:CCCG:C	donor_gain	1.0000
5:81393987:CCCGC:C	donor_gain	1.0000
5:81332471:ACTC:A	donor_loss	0.9900
5:81332473:T:TC	donor_loss	0.9900
5:81332474:C:CG	donor_loss	0.9900
5:81332475:A:AC	donor_gain	0.9900
5:81332475:A:AT	donor_loss	0.9900
5:81332475:ACC:A	donor_gain	0.9900

AlphaMissense

3675 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:81345953:G:C	F235L	0.996
5:81345953:G:T	F235L	0.996
5:81345955:A:G	F235L	0.996
5:81371765:G:C	F81L	0.993
5:81371765:G:T	F81L	0.993
5:81371767:A:G	F81L	0.993
5:81371756:G:C	S84R	0.992
5:81371756:G:T	S84R	0.992
5:81371758:T:G	S84R	0.992
5:81345954:A:G	F235S	0.991
5:81344181:C:G	R320P	0.990
5:81347824:A:C	F201L	0.990
5:81347824:A:T	F201L	0.990
5:81347826:A:G	F201L	0.990
5:81344182:G:T	R320S	0.989
5:81359970:T:A	R143S	0.989
5:81359970:T:G	R143S	0.989
5:81385826:G:T	A43D	0.989
5:81335784:A:G	W416R	0.988
5:81335784:A:T	W416R	0.988
5:81345906:A:T	V251D	0.986
5:81393999:G:T	A39D	0.986
5:81344960:A:C	F285L	0.984
5:81344960:A:T	F285L	0.984
5:81344962:A:G	F285L	0.984
5:81344969:G:C	N282K	0.984
5:81344969:G:T	N282K	0.984
5:81385791:A:G	S55P	0.984
5:81394015:A:G	W34R	0.984
5:81394015:A:T	W34R	0.984

dbSNP variants (sampled 300 via entrez): RS1000061332 (5:81339784 T>C), RS1000070864 (5:81345194 C>A,T), RS1000106751 (5:81386200 T>C), RS1000145122 (5:81388049 G>A,C), RS1000220549 (5:81386219 C>T), RS1000243304 (5:81393389 T>C), RS1000279185 (5:81362191 G>A), RS1000280013 (5:81339997 C>T), RS1000293835 (5:81333588 T>C), RS1000331796 (5:81309861 C>A,G,T), RS1000381565 (5:81332927 A>G,T), RS1000392817 (5:81373863 C>T), RS1000434705 (5:81387736 G>A,C), RS1000457761 (5:81322065 A>G), RS1000485905 (5:81346065 T>C)

Disease associations

OMIM: gene MIM:614315 | 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
GCST008103_26	Bipolar disorder	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Valproic Acid	increases expression, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
chlortoluron	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression, affects cotreatment	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Farnesol	affects cotreatment, increases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1
Glycocholic Acid	affects cotreatment, decreases expression	1
Glycodeoxycholic Acid	decreases expression, affects cotreatment	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	increases expression	1
Tobacco Smoke Pollution	increases methylation	1
Triclosan	decreases expression, affects cotreatment	1
Oleic Acid	decreases expression, affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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