ACAT2

Summary

ACAT2 (acetyl-CoA acetyltransferase 2, HGNC:94) is a protein-coding gene on chromosome 6q25.3, encoding Acetyl-CoA acetyltransferase, cytosolic (Q9BWD1). Involved in the biosynthetic pathway of cholesterol.

The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 39 — RefSeq curated summary.

At a glance

• Gene–disease (curated): acetyl-CoA acetyltransferase-2 deficiency (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 106 total — 15 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes
• MANE Select transcript: NM_005891

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:94
Approved symbol	ACAT2
Name	acetyl-CoA acetyltransferase 2
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000120437
Ensembl biotype	protein_coding
Entrez	39

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000367048, ENST00000467951, ENST00000472052, ENST00000869581, ENST00000869582, ENST00000869583, ENST00000869584, ENST00000869585, ENST00000869586, ENST00000869587, ENST00000869588, ENST00000869589, ENST00000869590, ENST00000869591, ENST00000934470, ENST00000934471, ENST00000934472, ENST00000934473, ENST00000934474, ENST00000942453

RefSeq mRNA: 2 — MANE Select: NM_005891 NM_001303253, NM_005891

CCDS: CCDS5268

Canonical transcript exons

ENST00000367048 — 9 exons

Exon	Start	End
ENSE00000765642	159775170	159775313
ENSE00000765643	159776150	159776272
ENSE00001510952	159762045	159762142
ENSE00001923516	159778659	159779112
ENSE00003507618	159767005	159767186
ENSE00003528567	159768511	159768628
ENSE00003534886	159778170	159778280
ENSE00003610929	159762919	159763053
ENSE00003693368	159777302	159777456

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.2848 / max 575.3258, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70983	66.3265	1820
70985	3.3816	1043
70984	0.7673	400
70987	0.6514	159
70986	0.1410	56
204276	0.0170	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.16	gold quality
ganglionic eminence	UBERON:0004023	98.15	gold quality
adrenal tissue	UBERON:0018303	97.94	gold quality
embryo	UBERON:0000922	97.64	gold quality
cortical plate	UBERON:0005343	96.84	gold quality
pons	UBERON:0000988	95.36	gold quality
right lobe of liver	UBERON:0001114	95.04	gold quality
upper leg skin	UBERON:0004262	94.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.41	gold quality
liver	UBERON:0002107	94.17	gold quality
mucosa of transverse colon	UBERON:0004991	94.16	gold quality
esophagus mucosa	UBERON:0002469	93.83	gold quality
islet of Langerhans	UBERON:0000006	93.66	gold quality
spinal cord	UBERON:0002240	93.56	gold quality
prefrontal cortex	UBERON:0000451	93.52	gold quality
sperm	CL:0000019	93.05	gold quality
oocyte	CL:0000023	92.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.79	gold quality
male germ cell	CL:0000015	92.19	gold quality
right testis	UBERON:0004534	92.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.96	gold quality
rectum	UBERON:0001052	91.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.75	gold quality
right frontal lobe	UBERON:0002810	91.64	gold quality
secondary oocyte	CL:0000655	91.60	gold quality
left testis	UBERON:0004533	91.33	gold quality
cingulate cortex	UBERON:0003027	91.08	gold quality
mammalian vulva	UBERON:0000997	91.02	gold quality
anterior cingulate cortex	UBERON:0009835	90.95	gold quality
testis	UBERON:0000473	90.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	40.98
E-MTAB-6819	no	1774.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, FOXO1, HNF1A, HNF4A, NR0B2, SREBF1

miRNA regulators (miRDB)

42 targeting ACAT2, 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-4789-3P	99.99	70.75	2484
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107

Literature-anchored findings (GeneRIF, showing 6)

• Data describe the high resolution structure of human cytosolic acetoacetyl-CoA thiolase (CT), both unliganded (at 2.3 angstroms resolution) and in complex with CoA (at 1.6 angstroms resolution). (PMID:15733928)
• The increased NPC1L1 and ACAT2 mRNA levels in gallstone patients might indicate an upregulated absorption and esterification of cholesterol in the small intestine. (PMID:19071091)
• Reduced ACAT2 is associated with impaired butyrate oxidation in ulcerative colitis. (PMID:21987487)
• Results show that DLAT and ACAT2 as upstream acetyltransferases of K76 and K294 in 6PGD protein. (PMID:25042803)
• results demonstrate that the low-level expression of human ACAT2 gene with specific CpG-hypomethylated promoter is regulated by the C/EBP transcription factors in monocytic cells, and imply that the lowly expressed ACAT2 catalyzes the synthesis of certain CE/SE that are assembled into lipoproteins for the secretion (PMID:27688151)
• Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2. (PMID:34036483)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	acat2	ENSDARG00000007127
mus_musculus	Acat2	ENSMUSG00000023832
mus_musculus	Acat3	ENSMUSG00000062480
rattus_norvegicus	Acat2l1	ENSRNOG00000013975
rattus_norvegicus	Acat2	ENSRNOG00000019189
drosophila_melanogaster	Acat2	FBGN0035203

Paralogs (4): ACAA1 (ENSG00000060971), ACAT1 (ENSG00000075239), HADHB (ENSG00000138029), ACAA2 (ENSG00000167315)

Protein

Protein identifiers

Acetyl-CoA acetyltransferase, cytosolic — Q9BWD1 (reviewed: Q9BWD1)

Alternative names: Acetyl-CoA transferase-like protein, Cytosolic acetoacetyl-CoA thiolase

All UniProt accessions (1): Q9BWD1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the biosynthetic pathway of cholesterol.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm. Cytosol.

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the thiolase-like superfamily. Thiolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BWD1-1	1	yes
Q9BWD1-2	2

RefSeq proteins (2): NP_001290182, NP_005882* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002155	Thiolase	Family
IPR016039	Thiolase-like	Homologous_superfamily
IPR020610	Thiolase_AS	Active_site
IPR020613	Thiolase_CS	Conserved_site
IPR020616	Thiolase_N	Domain
IPR020617	Thiolase_C	Domain

Pfam: PF00108, PF02803

Enzyme classification (BRENDA):

• EC 2.3.1.9 — acetyl-CoA C-acetyltransferase (BRENDA: 44 organisms, 97 substrates, 66 inhibitors, 86 Km, 27 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETOACETYL-COA	0.0038–0.18	36
COA	0.0048–0.154	23
ACETYL-COA	0.0062–1.06	20
ACETOACETYL-10-BIS-DEMETHYLPANTETHEINE 11-PIVALA	0.21	1
ACETOACETYL-S-(11-METHOXYMETHYL)PANTETHEINE	0.12	1
ACETOACETYL-S-(11-T-BUTYLDIMETHYLSILYL)PANTETHEI	0.074	1
ACETOACETYL-S-(D-PANTETHEINE) 11-PIVALATE	0.073	1
ACETOACETYL-S-HOMOPANTETHEINE 12-PIVALATE	0.25	1
ACETOACETYL-S-PANTETHEINE	0.46	1
3-KETOBUTYRYLDITHIO-COA	—	0
ACETOACETYL-10-BIS-DEMETHYLPANTETHEINE 11-PIVALO	—	0
ACETOACETYL-S-(L-PANTETHEINE) 11-PIVALATE	—	0
THIOLYTIC CLEAVAGE	—	0

Catalyzed reactions (Rhea), 1 shown:

• 2 acetyl-CoA = acetoacetyl-CoA + CoA (RHEA:21036)

UniProt features (52 total): helix 18, strand 12, turn 6, modified residue 4, sequence conflict 3, binding site 3, active site 2, chain 1, splice variant 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1WL4	X-RAY DIFFRACTION	1.55
1WL5	X-RAY DIFFRACTION	2.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWD1-F1	97.28	0.98

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 92 (acyl-thioester intermediate); 383 (proton donor/acceptor); 353 (increases nucleophilicity of active site cys)

Ligand- & substrate-binding residues (3): 223; 226; 252

Post-translational modifications (4): 235, 1, 200, 233

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9969896	Lanosterol biosynthesis
R-HSA-191273	Cholesterol biosynthesis
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 238 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, SHEPARD_BMYB_MORPHOLINO_DN, PUJANA_CHEK2_PCC_NETWORK, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, chr6q25, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP

GO Biological Process (3): lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), farnesyl diphosphate biosynthetic process, mevalonate pathway (GO:0010142)

GO Molecular Function (5): acetyl-CoA C-acetyltransferase activity (GO:0003985), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cholesterol biosynthesis	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
phospholipid biosynthetic process	1
terpenoid biosynthetic process	1
farnesyl diphosphate metabolic process	1
isoprenoid biosynthetic process via mevalonate	1
acetyl-CoA C-acyltransferase activity	1
C-acetyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

2122 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACAT2	HMGCR	P04035	815
ACAT2	HMGCS1	Q01581	794
ACAT2	MVD	P53602	782
ACAT2	MVK	Q03426	731
ACAT2	GGPS1	O95749	701
ACAT2	TCP1	P17987	698
ACAT2	IDI2	Q9BXS1	682
ACAT2	IDI1	Q13907	666
ACAT2	LSS	P48449	655
ACAT2	FDPS	P14324	652
ACAT2	PMVK	Q15126	649
ACAT2	FDFT1	P37268	647
ACAT2	SQLE	Q14534	621
ACAT2	HMGCS2	P54868	608
ACAT2	ECHS1	P30084	578

IntAct

45 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
ACAT2	LNX1	psi-mi:“MI:0915”(physical association)	0.560
LNX1	ACAT2	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	ACAT2	psi-mi:“MI:0915”(physical association)	0.560
ACAT2	WWOX	psi-mi:“MI:0915”(physical association)	0.560
ACAT2	ACAT2	psi-mi:“MI:0915”(physical association)	0.550
TERF1	ACAT2	psi-mi:“MI:0915”(physical association)	0.510
ACAT2	ACAT1	psi-mi:“MI:0915”(physical association)	0.400
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
MLST8	LYPLA2	psi-mi:“MI:0914”(association)	0.350
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
E2F1	CLIC1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
FAM170A	MCM3AP	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
PCDHGA9	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
TNIK	ACAT2	psi-mi:“MI:0915”(physical association)	0.000
ATG5	ACAT2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (83): ACAT2 (Two-hybrid), LNX1 (Two-hybrid), ACAT2 (Affinity Capture-RNA), ACAT2 (Affinity Capture-MS), ACAT1 (Affinity Capture-MS), TRAPPC8 (Affinity Capture-MS), ACAT2 (Co-fractionation), ACAT2 (Co-fractionation), ACAT2 (Co-fractionation), ACAT2 (Co-fractionation), ACAT2 (Co-fractionation), HADH (Co-fractionation), HSPE1 (Co-fractionation), PCBP1 (Co-fractionation), PCBP2 (Co-fractionation)

ESM2 similar proteins: A0A1D8PH52, A0R1Y7, B0XMC1, B0YA65, I1RMA2, I1RY81, P07097, P10551, P13437, P14611, P33290, P33291, P41338, P42765, P44873, P45363, P45369, P45855, P46707, P50174, P54810, Q04677, Q05493, Q0AVM3, Q12598, Q22100, Q2FJQ9, Q2G124, Q2YVF5, Q3T0R7, Q4WCL5, Q4WLA8, Q5HIU0, Q5HS07, Q5RES5, Q5XI22, Q6GCB8, Q6GJW4, Q6L8K7, Q7A7L2

Diamond homologs: A0A1D8PH52, A0KEL0, A0R1Y7, A1TZR8, A5W6G9, A6VVM8, B0XMC1, B0YA65, B5FEW7, B6EGU1, I1RMA2, I1RY81, O32177, P07097, P07871, P10551, P13437, P14611, P17764, P24752, P28790, P41338, P42765, P44873, P45359, P45363, P45369, P45855, P46707, P50174, P54810, P66927, P73825, P76461, P9WG68, P9WG69, Q04677, Q0AVM3, Q0KBP1, Q0VNZ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	0
Uncertain significance	63
Likely benign	9
Benign	6

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
148306	GRCh38/hg38 6q25.2-27(chr6:154539655-170714507)x1	Pathogenic
148765	GRCh38/hg38 6q25.3-26(chr6:155378049-163133499)x1	Pathogenic
1527308	GRCh37/hg19 6q25.2-26(chr6:153207930-164322346)	Pathogenic
153525	GRCh38/hg38 6q25.2-27(chr6:152793402-170610394)x1	Pathogenic
1703663	GRCh37/hg19 6q25.3-27(chr6:159121459-170919482)	Pathogenic
2427078	NC_000006.11:g.(?158532398)(162868359_?)del	Pathogenic
3148927	GRCh37/hg19 6q25.2-27(chr6:152853218-170914297)x1	Pathogenic
3391846	GRCh37/hg19 6q24.2-27(chr6:144561123-170919482)x3	Pathogenic
3391892	GRCh37/hg19 6q25.2-27(chr6:153777725-170919482)x1	Pathogenic
3391893	GRCh37/hg19 6q25.3-27(chr6:158471960-170919482)x1	Pathogenic
394997	GRCh37/hg19 6q25.1-27(chr6:151214792-170892243)x3	Pathogenic
57020	GRCh38/hg38 6q24.1-27(chr6:141132990-169339571)x3	Pathogenic
58453	GRCh38/hg38 6q25.2-27(chr6:154118058-170602152)x1	Pathogenic
58455	GRCh38/hg38 6q25.3-27(chr6:159454639-170612001)x1	Pathogenic
666538	NM_000019.3:c.(72+1_73-1)_(344+1_345-1)del	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2571 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:159778227:T:C	F324L	0.995
6:159778229:T:A	F324L	0.995
6:159778229:T:G	F324L	0.995
6:159767027:A:C	R71S	0.988
6:159767027:A:T	R71S	0.988
6:159778690:G:T	G352V	0.988
6:159767158:T:A	V115D	0.985
6:159778694:C:A	H353Q	0.985
6:159778694:C:G	H353Q	0.985
6:159778806:G:C	A391P	0.985
6:159776252:T:A	V246D	0.984
6:159778690:G:A	G352D	0.984
6:159778693:A:G	H353R	0.982
6:159767164:G:A	G117E	0.981
6:159767173:A:T	E120V	0.981
6:159767181:A:C	S123R	0.981
6:159767183:C:A	S123R	0.981
6:159767183:C:G	S123R	0.981
6:159777310:G:C	D256H	0.981
6:159767026:G:C	R71T	0.980
6:159776227:T:C	F238L	0.980
6:159776229:T:A	F238L	0.980
6:159776229:T:G	F238L	0.980
6:159776266:G:C	A251P	0.980
6:159778814:T:G	C393W	0.980
6:159778717:G:C	R361P	0.979
6:159777323:C:A	A260D	0.978
6:159777322:G:C	A260P	0.977
6:159777443:C:A	A300D	0.977
6:159778692:C:G	H353D	0.977

dbSNP variants (sampled 300 via entrez): RS1000053818 (6:159772788 A>T), RS1000179727 (6:159768777 G>C,T), RS1000216280 (6:159762331 T>A,C), RS1000312919 (6:159762505 T>A,C), RS1000550825 (6:159775040 C>A), RS1000603003 (6:159774607 C>T), RS1001181003 (6:159763588 T>A,G), RS1001318385 (6:159764027 G>A), RS1001342220 (6:159776488 G>C), RS1001445686 (6:159770207 C>G), RS1001603276 (6:159776215 C>A,G), RS1001898489 (6:159769882 T>A), RS1002138460 (6:159766400 C>CA,CG), RS1002190911 (6:159766044 C>T), RS1002324107 (6:159765330 G>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:614739, MIM:617140, MIM:614055, MIM:203750

GenCC curated gene-disease

Disease	Classification	Inheritance
acetyl-CoA acetyltransferase-2 deficiency	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
acetyl-CoA acetyltransferase-2 deficiency	No Known Disease Relationship	UD

Mondo (5): hydrocephalus (MONDO:0001150), 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MONDO:0013875), ZTTK syndrome (MONDO:0014936), acetyl-CoA acetyltransferase-2 deficiency (MONDO:0013548), beta-ketothiolase deficiency (MONDO:0008760)

Orphanet (3): MEGDEL syndrome (Orphanet:352328), ZTTK syndrome (Orphanet:500150), Beta-ketothiolase deficiency (Orphanet:134)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0002072	Chorea
HP:0002151	Increased circulating lactate concentration
HP:0003542	Increased circulating pyruvate concentration
HP:0003745	Sporadic

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006218_56	Erosive tooth wear (severe vs non-severe)	3.000000e-08
GCST007052_1	Lipoprotein (a) levels	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006849	Hydrocephalus	C10.228.140.602
C535434	Beta ketothiolase deficiency (supp.)
C536005	Cytosolic acetoacetyl-CoA thiolase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2240 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Lanosterol biosynthesis pathway

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
K-604	Inhibition	3.89	pIC50

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.66	IC50	22	nM	CHEMBL5573112
7.66	IC50	22	nM	CHEMBL2094750
7.60	IC50	25	nM	CHEMBL5583807
6.77	IC50	171	nM	CHEMBL5569869
6.57	IC50	269	nM	CHEMBL5569963

PubChem BioAssay actives

5 with measured affinity, of 7 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(2-chlorophenyl)methyl]spiro[1,4-dihydroquinoxaline-3,4’-piperidine]-2-imine	2106965: Inhibition of Acetyl-CoA acetyltransferase (unknown origin)	ic50	0.0220	uM
N-[(3-chlorophenyl)methyl]spiro[1,4-dihydroquinoxaline-3,4’-piperidine]-2-imine	2106965: Inhibition of Acetyl-CoA acetyltransferase (unknown origin)	ic50	0.0220	uM
N-[(2-methylphenyl)methyl]spiro[1,4-dihydroquinoxaline-3,4’-piperidine]-2-imine	2106965: Inhibition of Acetyl-CoA acetyltransferase (unknown origin)	ic50	0.0250	uM
N-[(2-chlorophenyl)methyl]-4’-methylspiro[1,4-dihydroquinoxaline-3,1’-cyclohexane]-2-imine	2106965: Inhibition of Acetyl-CoA acetyltransferase (unknown origin)	ic50	0.1710	uM
N-[(4-methylphenyl)methyl]spiro[1,4-dihydroquinoxaline-3,1’-cyclohexane]-2-imine	2106965: Inhibition of Acetyl-CoA acetyltransferase (unknown origin)	ic50	0.2690	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	7
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
Cyclosporine	decreases expression, increases expression	6
bisphenol A	affects cotreatment, increases methylation, decreases expression, affects expression	5
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression	5
perfluorooctanoic acid	affects cotreatment, decreases expression	2
cupric chloride	decreases expression	2
cyproconazole	decreases expression, increases expression	2
perfluoro-n-nonanoic acid	decreases expression, affects cotreatment	2
bisphenol S	increases expression	2
Acetaminophen	decreases expression	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
GSK-J4	decreases expression	1
afuresertib	increases expression	1
bisphenol F	increases expression	1
lly-283	decreases expression	1
dicrotophos	decreases expression	1
beauvericin	decreases expression, affects cotreatment	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
isoquercitrin	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
periodate-oxidized adenosine	affects expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5368896	Binding	Inhibition of recombinant human ACAT2	Discovery of 12 (BMS-986172) as a Highly Potent MGAT2 Inhibitor that Achieved Targeted Efficacious Exposures at a Low Human Dose for the Treatment of Metabolic Disorders. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1PG	HAP1 ACAT2 (-) 1	Cancer cell line	Male
CVCL_E1PH	HAP1 ACAT2 (-) 2	Cancer cell line	Male
CVCL_E1PI	HAP1 ACAT2 (-) 3	Cancer cell line	Male
CVCL_E1PJ	HAP1 ACAT2 (-) 4	Cancer cell line	Male
CVCL_UQ02	Abcam Jurkat ACAT2 KO	Cancer cell line	Male
CVCL_WQ86	Abcam K-562 ACAT2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01323764	PHASE4	COMPLETED	ShuntCheck Versus Radionuclide in Evaluating Shunt Function in Symptomatic NPH Patients
NCT01685450	PHASE4	UNKNOWN	NIMIP: Non Invasive Measurement of the Intracranial Pressure
NCT03513757	PHASE4	COMPLETED	Dexmedetomidine and Propofol for Pediatric MRI Sedation
NCT07547826	PHASE4	NOT_YET_RECRUITING	Efficacy and Cost-Effectiveness of Topical Vancomycin Powder in Preventing Pediatric Ventriculoperitoneal Shunt Infections Across Different Etiologies
NCT00196196	PHASE3	COMPLETED	A Precision and Accuracy Study of the Codman Valve Position Verification (VPV) System.
NCT00286104	PHASE3	COMPLETED	Impact of Ventricular Catheter Used With Antimicrobial Agents on Patients With a Ventricular Catheter
NCT01936272	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Shunt vs ETV/CPC for PIH in Ugandan Infants
NCT02425761	PHASE3	UNKNOWN	The CSF Shunt Entry Site Trial
NCT02512809	PHASE3	TERMINATED	Isoflurane-induced Neuroinflammation in Children With Hydrocephalus
NCT04177914	PHASE3	RECRUITING	HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants
NCT00652470	PHASE2	COMPLETED	A Study Comparing Two Treatments for Infants With Hydrocephalus
NCT05001750	PHASE1	RECRUITING	Prophylactic Antibiotics Useful With Antibiotic Impregnated External Ventricular Drains (EVDs)?
NCT01878136	PHASE1/PHASE2	WITHDRAWN	Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage
NCT05476874	PHASE1/PHASE2	UNKNOWN	Improvement of Peritoneal Catheter Placement in VPS With a Splitable Trocar
NCT00001327	Not specified	COMPLETED	Establishing the Physiology of Syringomyelia
NCT00280904	Not specified	COMPLETED	A Registry for Comparing Catheter-Related Infection Rates Among Various Shunt Systems in the Treatment of Hydrocephalus
NCT00651950	Not specified	WITHDRAWN	Bench Study of Transcutaneous Hydrocephalic Shunt Flow Sensor Alignment Accuracy and Repeatability
NCT00652197	Not specified	COMPLETED	Monitoring Patient Cerebro-Spinal Fluid Drainage With an Ultrasonic Flow Sensor
NCT00652249	Not specified	WITHDRAWN	Diagnosing Malfunctioning Hydrocephalic Shunt Valves With a Flow Sensor
NCT00692744	Not specified	COMPLETED	Quality of Life in Elderly After Aneurysmal Subarachnoid Hemorrhage (SAH)
NCT00743457	Not specified	COMPLETED	Study of Ultrasound of the Eye for Children With Suspected Shunt Failure
NCT00875758	Not specified	COMPLETED	Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants
NCT00886054	Not specified	UNKNOWN	The Prediction of Intracranial Pressure and Clinical Outcome by Transcranial Doppler in Neurocritical Patients
NCT00946127	Not specified	TERMINATED	ETV Versus Shunt Surgery in Normal Pressure Hydrocephalus
NCT01108965	Not specified	COMPLETED	Study of Shunt Flow Sensor Accuracy in Extra-ventricular Drains.
NCT01191307	Not specified	TERMINATED	Assess Specific Kinds of Children Challenges for Neurologic Devices Study
NCT01556178	Not specified	COMPLETED	Blood and Cerebrospinal Fluid for Pediatric Brain Tumor Research
NCT01797627	Not specified	COMPLETED	Ventricular Size Involvement in Neuropsychological Outcomes in Pediatric Hydrocephalus
NCT01799018	Not specified	COMPLETED	Role of Proteomics and Metallomics in Cerebral Vasospasm Following Subarachnoid Hemorrhage
NCT01811589	Not specified	COMPLETED	Guided Application of Ventricular Catheters
NCT01863329	Not specified	TERMINATED	Comparison of Optic Nerve Sheath Diameter on Retrobulbar Ultrasound Before and After Drainage of Cerebrospinal Fluid in Patient With Hydrocephalus
NCT01863381	Not specified	TERMINATED	Comparison of Continuous Non-Invasive and Invasive Intracranial Pressure Measurement
NCT01865149	Not specified	UNKNOWN	Comparison of Optic Nerve Sheath Diameter on Retrobulbar Ultrasonography Before and After Drainage of Cerebrospinal Fluid in Pediatric Patient With Hydrocephalus
NCT01973764	Not specified	TERMINATED	Intraventricular Drain Insertion: Comparison of Ultrasound-guided and Landmark-based Puncture of the Ventricular System
NCT01976559	Not specified	COMPLETED	Comparison of Continuous Noninvasive and Invasive Intracranial Pressure Measurement–Celda Infusion Subprotocol
NCT02067364	Not specified	UNKNOWN	CRT ShuntCheck Fit & Function Study
NCT02230124	Not specified	ACTIVE_NOT_RECRUITING	Magnetic Resonance Elastography in Hydrocephalus
NCT02381977	Not specified	COMPLETED	Prevalence of Acute Critical Neurological Disease in Children: a Global Epidemiological Assessment
NCT02404740	Not specified	COMPLETED	Noninvasive Intracranial Pressure and Hydrocephalus Patients
NCT02408757	Not specified	TERMINATED	Sonographic Monitoring of Weaning of Cerebrospinal Fluid Drainages