ACOT11

Summary

ACOT11 (acyl-CoA thioesterase 11, HGNC:18156) is a protein-coding gene on chromosome 1p32.3, encoding Acyl-coenzyme A thioesterase 11 (Q8WXI4). Has an acyl-CoA thioesterase activity with a preference for the long chain fatty acyl-CoA thioesters hexadecanoyl-CoA/palmitoyl-CoA and tetradecanoyl-CoA/myristoyl-CoA which are the main substrates in the mitochondrial beta-oxidation pathway.

This gene encodes a member of the acyl-CoA thioesterase family which catalyse the conversion of activated fatty acids to the corresponding non-esterified fatty acid and coenzyme A. Expression of a mouse homolog in brown adipose tissue is induced by low temperatures and repressed by warm temperatures. Higher levels of expression of the mouse homolog has been found in obesity-resistant mice compared with obesity-prone mice, suggesting a role of acyl-CoA thioesterase 11 in obesity. Alternative splicing results in transcript variants.

Source: NCBI Gene 26027 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 243 total — 4 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_147161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18156
Approved symbol	ACOT11
Name	acyl-CoA thioesterase 11
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	STARD14, BFIT, KIAA0707, BFIT1, THEM1
Ensembl gene	ENSG00000162390
Ensembl biotype	protein_coding
OMIM	606803
Entrez	26027

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000343744, ENST00000371316, ENST00000479837, ENST00000481208, ENST00000498228, ENST00000877323, ENST00000877324, ENST00000971238, ENST00000971239

RefSeq mRNA: 2 — MANE Select: NM_147161 NM_015547, NM_147161

CCDS: CCDS592, CCDS593

Canonical transcript exons

ENST00000343744 — 16 exons

Exon	Start	End
ENSE00001385652	54608957	54610329
ENSE00001424268	54548228	54548342
ENSE00003477798	54593941	54594039
ENSE00003485702	54594556	54594691
ENSE00003500331	54601269	54601413
ENSE00003512954	54584655	54584862
ENSE00003522249	54604346	54604429
ENSE00003575538	54599296	54599415
ENSE00003585291	54602669	54602724
ENSE00003589202	54605076	54605209
ENSE00003594861	54603871	54603937
ENSE00003598454	54592546	54592606
ENSE00003628535	54597259	54597415
ENSE00003639349	54607942	54608068
ENSE00003644172	54607134	54607265
ENSE00003676486	54585835	54585904

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 94.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.9017 / max 140.4186, expressed in 969 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2953	1.5770	343
2951	1.4720	625
2954	0.4475	214
2950	0.4053	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	94.24	gold quality
mucosa of transverse colon	UBERON:0004991	93.94	gold quality
buccal mucosa cell	CL:0002336	92.90	gold quality
duodenum	UBERON:0002114	91.28	gold quality
jejunal mucosa	UBERON:0000399	90.03	gold quality
heart left ventricle	UBERON:0002084	90.02	gold quality
cardiac ventricle	UBERON:0002082	89.74	gold quality
lower esophagus mucosa	UBERON:0035834	89.03	gold quality
ileal mucosa	UBERON:0000331	88.76	gold quality
renal medulla	UBERON:0000362	88.54	gold quality
pharyngeal mucosa	UBERON:0000355	88.18	gold quality
metanephros cortex	UBERON:0010533	87.11	gold quality
jejunum	UBERON:0002115	86.43	gold quality
small intestine	UBERON:0002108	86.02	gold quality
transverse colon	UBERON:0001157	85.88	gold quality
diaphragm	UBERON:0001103	85.59	silver quality
heart	UBERON:0000948	85.13	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.89	gold quality
esophagus mucosa	UBERON:0002469	84.83	gold quality
adult mammalian kidney	UBERON:0000082	84.66	gold quality
body of tongue	UBERON:0011876	84.52	gold quality
left ventricle myocardium	UBERON:0006566	84.43	gold quality
tongue squamous epithelium	UBERON:0006919	84.23	gold quality
cervix squamous epithelium	UBERON:0006922	84.16	silver quality
rectum	UBERON:0001052	83.71	gold quality
right lobe of thyroid gland	UBERON:0001119	83.00	gold quality
gluteal muscle	UBERON:0002000	83.00	silver quality
vena cava	UBERON:0004087	82.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.90	gold quality
pigmented layer of retina	UBERON:0001782	82.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	91.41
E-ANND-3	yes	6.47
E-CURD-135	no	1096.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ATF4, FOXC1, GATA4, IRF6, IRF8, JUN, MYB, MYBL1, NKX2-5, TCF3, TP63, YBX1

Literature-anchored findings (GeneRIF, showing 3)

• BFIT supports the transition of thermogenic brown adipose tissue towards increased metabolic activity, probably through alteration of intracellular fatty acyl-CoA concentration. (PMID:11696000)
• The N-terminal region of human fat inducible thioesterase variant 2 constitutes a mitochondrial location signal sequence, which undergoes mitochondrion-dependent posttranslational cleavage. (PMID:22897136)
• Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine. (PMID:32820071)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	acot11b	ENSDARG00000042122
danio_rerio	acot11a	ENSDARG00000058229
mus_musculus	Acot11	ENSMUSG00000034853
rattus_norvegicus	Acot11	ENSRNOG00000007837

Paralogs (2): ACOT7 (ENSG00000097021), ACOT12 (ENSG00000172497)

Protein

Protein identifiers

Acyl-coenzyme A thioesterase 11 — Q8WXI4 (reviewed: Q8WXI4)

Alternative names: Acyl-CoA thioester hydrolase 11, Adipose-associated thioesterase, Brown fat-inducible thioesterase, Palmitoyl-coenzyme A thioesterase

All UniProt accessions (1): Q8WXI4

UniProt curated annotations — full annotation on UniProt →

Function. Has an acyl-CoA thioesterase activity with a preference for the long chain fatty acyl-CoA thioesters hexadecanoyl-CoA/palmitoyl-CoA and tetradecanoyl-CoA/myristoyl-CoA which are the main substrates in the mitochondrial beta-oxidation pathway.

Subcellular location. Mitochondrion matrix. Cytoplasm.

Tissue specificity. Isoform 1 is predominantly expressed in skeletal muscle, liver, testis, stomach, spleen, lung and brain. Isoform 2 is predominantly expressed in kidney, uterus, hibernoma and white adipose tissue.

Induction. By cold exposure and repressed by heat exposure.

Pathway. Lipid metabolism; fatty acid metabolism.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WXI4-1	1, BFIT1	yes
Q8WXI4-2	2, BFIT2

RefSeq proteins (2): NP_056362, NP_671517* (*=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

Catalyzed reactions (Rhea), 4 shown:

• hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+) (RHEA:16645)
• dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+) (RHEA:30135)
• butanoyl-CoA + H2O = butanoate + CoA + H(+) (RHEA:40111)
• tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+) (RHEA:40119)

UniProt features (37 total): strand 12, sequence variant 5, helix 5, binding site 4, domain 3, modified residue 2, sequence conflict 2, transit peptide 1, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3FO5	X-RAY DIFFRACTION	2
6VVQ	X-RAY DIFFRACTION	3.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXI4-F1	81.31	0.56

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): 91–93; 120–122; 181; 271–273

Post-translational modifications (2): 25, 15

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: 138 (showing top): GOBP_RESPONSE_TO_COLD, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, REACTOME_MITOCHONDRIAL_FATTY_ACID_BETA_OXIDATION, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_TEMPERATURE_HOMEOSTASIS, GOCC_MITOCHONDRIAL_MATRIX, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (7): fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), response to temperature stimulus (GO:0009266), response to cold (GO:0009409), intracellular signal transduction (GO:0035556), negative regulation of cold-induced thermogenesis (GO:0120163), lipid metabolic process (GO:0006629)

GO Molecular Function (7): lipid binding (GO:0008289), fatty acyl-CoA hydrolase activity (GO:0047617), carboxylic ester hydrolase activity (GO:0052689), long-chain fatty acyl-CoA hydrolase activity (GO:0052816), protein binding (GO:0005515), hydrolase activity (GO:0016787), thiolester hydrolase activity (GO:0016790)

GO Cellular Component (5): cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), extracellular exosome (GO:0070062), mitochondrion (GO:0005739)

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
intracellular anatomical structure	2
binding	2
hydrolase activity, acting on ester bonds	2
cellular anatomical structure	2
cytoplasm	2
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
response to abiotic stimulus	1
response to stress	1
response to temperature stimulus	1
signal transduction	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
acyl-CoA hydrolase activity	1
fatty acyl-CoA hydrolase activity	1
catalytic activity	1
mitochondrion	1
intracellular organelle lumen	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACOT11	ACOT13	Q9NPJ3	722
ACOT11	PCTP	Q9UKL6	613
ACOT11	ACOT8	O14734	607
ACOT11	ACOT4	Q8N9L9	514
ACOT11	STARD6	P59095	501
ACOT11	ACOT9	Q9Y305	500
ACOT11	THEM5	Q8N1Q8	496
ACOT11	ACOT2	P49753	490
ACOT11	STARD9	Q9P2P6	479
ACOT11	STARD5	P59094	479
ACOT11	STARD8	Q92502	479
ACOT11	ACOT1	Q86TX2	476
ACOT11	STARD4	Q96DR4	447
ACOT11	STARD7	Q9NQZ5	427
ACOT11	AASDH	Q4L235	424

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ACOT12	INPPL1	psi-mi:“MI:0914”(association)	0.530
rep	ACOT11	psi-mi:“MI:0915”(physical association)	0.490
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CCP110	A2ML1	psi-mi:“MI:0914”(association)	0.350
TEKT2	METAP2	psi-mi:“MI:0914”(association)	0.350
ACOT11	THUMPD3	psi-mi:“MI:0914”(association)	0.350
TEKT2	MYH1	psi-mi:“MI:0914”(association)	0.350
ACOT11	TUBA1A	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350

BioGRID (26): THUMPD3 (Affinity Capture-MS), ACOT11 (Affinity Capture-MS), ACOT11 (Affinity Capture-MS), ACOT11 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), ACOT11 (Two-hybrid), ACOT11 (Two-hybrid), ACOT11 (Two-hybrid), ACOT11 (Two-hybrid), ACOT11 (Two-hybrid), ACOT11 (Two-hybrid), ACOT11 (Two-hybrid), MKRN3 (Two-hybrid), HGS (Two-hybrid), FGFBP2 (Affinity Capture-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: O00154, O66120, O84540, P0A0Q7, P0A0Q8, P0A1A1, P0A1A2, P0A8Z0, P0A8Z1, P0A8Z2, P44886, P49851, Q64559, Q89AL4, Q8VHQ9, Q8WXI4, Q8WYK0, Q91V12, Q99NB7, Q9DBK0, Q9PJK7, Q9Z7Q0, S4TF94, Q6ZUV0, S4TDL2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	181
Likely benign	15
Benign	10

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
150647	GRCh38/hg38 1p32.3-31.3(chr1:53627272-64248854)x1	Pathogenic
394094	GRCh37/hg19 1p32.3(chr1:51729573-55164001)x1	Pathogenic
59968	GRCh38/hg38 1p32.3-31.3(chr1:53738212-61439648)x1	Pathogenic
59969	GRCh38/hg38 1p32.3(chr1:54207426-54756958)x1	Pathogenic
153325	GRCh38/hg38 1p32.3-31.3(chr1:52787503-67339873)x3	Likely pathogenic
3062755	GRCh37/hg19 1p33-32.2(chr1:47493178-57042671)x3	Likely pathogenic

SpliceAI

5185 predictions. Top by Δscore:

Variant	Effect	Δscore
1:54584858:GTCCG:G	donor_gain	1.0000
1:54584859:TCCGG:T	donor_loss	1.0000
1:54584860:CCGGT:C	donor_loss	1.0000
1:54584861:CGG:C	donor_loss	1.0000
1:54584862:GGTAA:G	donor_loss	1.0000
1:54584863:G:C	donor_loss	1.0000
1:54584863:G:GG	donor_gain	1.0000
1:54584864:T:G	donor_loss	1.0000
1:54585823:T:TA	acceptor_gain	1.0000
1:54585826:T:A	acceptor_gain	1.0000
1:54585830:A:AG	acceptor_gain	1.0000
1:54592545:GT:G	acceptor_gain	1.0000
1:54593928:T:A	acceptor_gain	1.0000
1:54593939:A:AC	acceptor_loss	1.0000
1:54593939:A:AG	acceptor_gain	1.0000
1:54593939:AG:A	acceptor_gain	1.0000
1:54593939:AGGT:A	acceptor_gain	1.0000
1:54593939:AGGTG:A	acceptor_gain	1.0000
1:54593940:G:GA	acceptor_gain	1.0000
1:54593940:GG:G	acceptor_gain	1.0000
1:54593940:GGT:G	acceptor_gain	1.0000
1:54593940:GGTG:G	acceptor_gain	1.0000
1:54593940:GGTGG:G	acceptor_gain	1.0000
1:54594036:CAAG:C	donor_loss	1.0000
1:54594037:AAGG:A	donor_loss	1.0000
1:54594040:G:GA	donor_loss	1.0000
1:54594546:T:A	acceptor_gain	1.0000
1:54594547:G:A	acceptor_gain	1.0000
1:54594550:C:A	acceptor_gain	1.0000
1:54594554:A:AG	acceptor_gain	1.0000

AlphaMissense

3907 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:54584851:C:A	A77D	0.998
1:54592584:G:C	R117P	0.998
1:54592589:T:C	F119L	0.998
1:54592591:C:A	F119L	0.998
1:54592591:C:G	F119L	0.998
1:54594623:G:C	R180P	0.998
1:54597328:T:A	V226D	0.998
1:54597363:T:C	F238L	0.998
1:54597365:T:A	F238L	0.998
1:54597365:T:G	F238L	0.998
1:54599345:T:C	F272L	0.998
1:54599347:C:A	F272L	0.998
1:54599347:C:G	F272L	0.998
1:54584835:T:A	W72R	0.997
1:54584835:T:C	W72R	0.997
1:54585860:T:G	C89W	0.997
1:54597400:C:A	A250D	0.997
1:54584862:G:C	A81P	0.996
1:54592571:G:C	A113P	0.996
1:54592598:A:C	S122R	0.996
1:54592600:C:A	S122R	0.996
1:54592600:C:G	S122R	0.996
1:54594626:G:C	R181P	0.996
1:54597347:T:A	N232K	0.996
1:54597347:T:G	N232K	0.996
1:54597367:G:A	G239E	0.996
1:54597412:C:A	A254D	0.996
1:54599346:T:C	F272S	0.996
1:54602704:A:C	R355S	0.996
1:54602704:A:T	R355S	0.996

dbSNP variants (sampled 300 via entrez): RS1000003461 (1:54560783 G>A), RS1000015136 (1:54602073 G>A,T), RS1000062244 (1:54638515 G>A), RS1000067788 (1:54602270 A>G), RS1000094973 (1:54554448 C>T), RS1000138150 (1:54623836 G>A), RS1000157062 (1:54623509 C>G,T), RS1000173674 (1:54603845 A>C), RS1000174730 (1:54575144 C>T), RS1000206869 (1:54579699 G>A), RS1000216513 (1:54570680 C>T), RS1000329954 (1:54598075 T>C), RS1000418422 (1:54586536 A>G), RS1000438088 (1:54560912 G>A,C), RS1000516849 (1:54638774 C>T)

Disease associations

OMIM: gene MIM:606803 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002790_1	Food allergy	3.000000e-07
GCST004029_6	Angiotensin-converting enzyme inhibitor intolerance	6.000000e-06
GCST004371_3	Rate of cognitive decline in mild cognitive impairment (time interaction)	3.000000e-11
GCST004485_6	Survival in pancreatic cancer	2.000000e-06
GCST008163_562	Height	2.000000e-06
GCST008748_8	Epigenetic age acceleration in alcohol use disorder	3.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007016	food allergy measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0007710	cognitive decline measurement
EFO:0008336	disease progression measurement
EFO:0000638	overall survival
EFO:0000473	epigenetic status
EFO:0022597	aging

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Tretinoin	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
lead acetate	decreases expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Copper	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

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