ACAA2

Summary

ACAA2 (acetyl-CoA acyltransferase 2, HGNC:83) is a protein-coding gene on chromosome 18q21.1, encoding 3-ketoacyl-CoA thiolase, mitochondrial (P42765). In the production of energy from fats, this is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA.

The encoded protein catalyzes the last step of the mitochondrial fatty acid beta-oxidation spiral. Unlike most mitochondrial matrix proteins, it contains a non-cleavable amino-terminal targeting signal.

Source: NCBI Gene 10449 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 100 total — 11 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:83
Approved symbol	ACAA2
Name	acetyl-CoA acyltransferase 2
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	DSAEC
Ensembl gene	ENSG00000167315
Ensembl biotype	protein_coding
OMIM	604770
Entrez	10449

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 retained_intron

ENST00000285093, ENST00000585948, ENST00000586100, ENST00000586485, ENST00000587994, ENST00000589432, ENST00000591171, ENST00000861144, ENST00000861145, ENST00000861146, ENST00000861147, ENST00000861148, ENST00000861149, ENST00000861150, ENST00000861151, ENST00000861152, ENST00000861153, ENST00000861154, ENST00000861155, ENST00000927719, ENST00000948654, ENST00000948655, ENST00000948656

RefSeq mRNA: 1 — MANE Select: NM_006111 NM_006111

CCDS: CCDS11939

Canonical transcript exons

ENST00000285093 — 10 exons

Exon	Start	End
ENSE00001151955	49785197	49785351
ENSE00001151963	49787291	49787361
ENSE00001151968	49791470	49791599
ENSE00001151973	49792152	49792327
ENSE00001151978	49794280	49794427
ENSE00001151985	49795765	49795881
ENSE00001321121	49813469	49813533
ENSE00002889798	49782164	49783931
ENSE00003657866	49797466	49797594
ENSE00003691369	49802687	49802853

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.5806 / max 1310.5331, expressed in 1806 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171921	32.9473	1737
171922	12.4244	1721
171925	7.1872	1601
171926	2.9936	1167
171929	2.8609	1018
171924	1.8537	1143
171927	1.3412	649
171923	0.5797	362
171928	0.3923	168

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.27	gold quality
mucosa of transverse colon	UBERON:0004991	98.77	gold quality
apex of heart	UBERON:0002098	98.19	gold quality
rectum	UBERON:0001052	98.01	gold quality
transverse colon	UBERON:0001157	98.01	gold quality
metanephros cortex	UBERON:0010533	97.97	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.24	gold quality
heart left ventricle	UBERON:0002084	97.08	gold quality
right atrium auricular region	UBERON:0006631	97.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.92	gold quality
mucosa of stomach	UBERON:0001199	96.88	gold quality
islet of Langerhans	UBERON:0000006	96.86	gold quality
ventricular zone	UBERON:0003053	96.77	gold quality
cardiac ventricle	UBERON:0002082	96.76	gold quality
gastrocnemius	UBERON:0001388	96.75	gold quality
right adrenal gland	UBERON:0001233	96.72	gold quality
right adrenal gland cortex	UBERON:0035827	96.65	gold quality
left adrenal gland	UBERON:0001234	96.63	gold quality
left adrenal gland cortex	UBERON:0035825	96.51	gold quality
omental fat pad	UBERON:0010414	96.40	gold quality
peritoneum	UBERON:0002358	96.35	gold quality
adrenal tissue	UBERON:0018303	96.20	gold quality
colonic epithelium	UBERON:0000397	96.19	gold quality
muscle of leg	UBERON:0001383	96.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.03	gold quality
gall bladder	UBERON:0002110	95.73	gold quality
body of pancreas	UBERON:0001150	95.72	gold quality
buccal mucosa cell	CL:0002336	95.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.69	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	30.41
E-HCAD-10	yes	29.97
E-CURD-112	no	3.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting ACAA2, 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-3910	99.95	71.13	2227
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-4435	95.90	65.47	1201

Literature-anchored findings (GeneRIF, showing 5)

• ACAA2 is a functional BNIP3 binding partner and provide a possible linkage between fatty acid metabolism and apoptosis of cells. (PMID:18371312)
• LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis. (PMID:36162992)
• Negative correlation between acetyl-CoA acyltransferase 2 and cetuximab resistance in colorectal cancer. (PMID:37310146)
• ACAA2 is a novel molecular indicator for cancers with neuroendocrine phenotype. (PMID:37798372)
• The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer. (PMID:38656551)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	acaa2	ENSDARG00000038881
		ENSDARG00000099056
mus_musculus	Acaa2	ENSMUSG00000036880
rattus_norvegicus	Acaa2	ENSRNOG00000013766
drosophila_melanogaster	yip2	FBGN0040064
caenorhabditis_elegans		WBGENE00009952

Paralogs (4): ACAA1 (ENSG00000060971), ACAT1 (ENSG00000075239), ACAT2 (ENSG00000120437), HADHB (ENSG00000138029)

Protein

Protein identifiers

3-ketoacyl-CoA thiolase, mitochondrial — P42765 (reviewed: P42765)

Alternative names: Acetyl-CoA acetyltransferase, Acetyl-CoA acyltransferase, Acyl-CoA hydrolase, mitochondrial, Beta-ketothiolase, Mitochondrial 3-oxoacyl-CoA thiolase, T1

All UniProt accessions (6): A0A0B4J2A4, P42765, K7EJ68, K7EJB1, K7EME0, K7ER88

UniProt curated annotations — full annotation on UniProt →

Function. In the production of energy from fats, this is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA. Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain unbranched 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms. Also catalyzes the condensation of two acetyl-CoA molecules into acetoacetyl-CoA and could be involved in the production of ketone bodies. Also displays hydrolase activity on various fatty acyl-CoAs. Thereby, could be responsible for the production of acetate in a side reaction to beta-oxidation. Abolishes BNIP3-mediated apoptosis and mitochondrial damage.

Subunit / interactions. Homotetramer. Interacts with BNIP3.

Subcellular location. Mitochondrion.

Pathway. Lipid metabolism; fatty acid beta-oxidation.

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

RefSeq proteins (1): NP_006102* (*=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
IPR020615	Thiolase_acyl_enz_int_AS	Active_site
IPR020616	Thiolase_N	Domain
IPR020617	Thiolase_C	Domain

Pfam: PF00108, PF02803

Enzyme classification (BRENDA):

• EC 2.3.1.16 — acetyl-CoA C-acyltransferase (BRENDA: 29 organisms, 107 substrates, 47 inhibitors, 51 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETOACETYL-COA	0.0092–0.394	16
ACETYL-COA	0.011–2.28	7
GLUTARYL-COA	2.2–2.33	4
MALONYL-COA	2.57–3.32	4
SUCCINYL-COA	0.59–2.1	4
COA	0.018–0.093	3
3-OXODECANOYL-COA	0.0018–0.0021	2
3-OXOHEXANOYL-COA	0.0083–0.028	2
3-OXOOCTANOYL-COA	0.0024–0.0088	2
3-OXODODECANOYL-COA	0.0093	1
3-OXOPENTANOYL-COA	0.059	1
COA-SH	0.0087	1

Catalyzed reactions (Rhea), 11 shown:

• hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+) (RHEA:16645)
• acetyl-CoA + H2O = acetate + CoA + H(+) (RHEA:20289)
• 2 acetyl-CoA = acetoacetyl-CoA + CoA (RHEA:21036)
• an acyl-CoA + acetyl-CoA = a 3-oxoacyl-CoA + CoA (RHEA:21564)
• dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+) (RHEA:30135)
• octanoyl-CoA + H2O = octanoate + CoA + H(+) (RHEA:30143)
• decanoyl-CoA + H2O = decanoate + CoA + H(+) (RHEA:40059)
• propanoyl-CoA + H2O = propanoate + CoA + H(+) (RHEA:40103)
• butanoyl-CoA + H2O = butanoate + CoA + H(+) (RHEA:40111)
• hexanoyl-CoA + H2O = hexanoate + CoA + H(+) (RHEA:40115)
• tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+) (RHEA:40119)

UniProt features (87 total): modified residue 35, helix 17, strand 15, turn 6, binding site 3, mutagenesis site 3, active site 2, sequence conflict 2, chain 1, transit peptide 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4C2J	X-RAY DIFFRACTION	2
4C2K	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42765-F1	97.49	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); 382 (proton donor/acceptor); 352 (increases nucleophilicity of active site cys)

Ligand- & substrate-binding residues (3): 224; 227; 251

Post-translational modifications (35): 45, 119, 121, 127, 136, 137, 137, 140, 143, 143, 171, 171, 191, 191, 209, 209, 211, 212, 214, 234 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
92	decreased acyl-coa hydrolase activity.
92	decreased acyl-coa hydrolase activity; when associated with a-382.
382	decreased acyl-coa hydrolase activity; when associated with s-92.

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: 337 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_LIPID_MODIFICATION, MYAATNNNNNNNGGC_UNKNOWN, GOBP_FATTY_ACID_CATABOLIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MITOCHONDRIAL_TRANSPORT, CEBPB_01, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_UP

GO Biological Process (7): fatty acid beta-oxidation (GO:0006635), cholesterol biosynthetic process (GO:0006695), cellular response to hypoxia (GO:0071456), negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901029), negative regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902109), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (10): RNA binding (GO:0003723), acetyl-CoA C-acetyltransferase activity (GO:0003985), acetyl-CoA hydrolase activity (GO:0003986), acetyl-CoA C-acyltransferase activity (GO:0003988), fatty acyl-CoA hydrolase activity (GO:0047617), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747), hydrolase activity (GO:0016787)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), nuclear body (GO:0016604), ciliary basal body (GO:0036064)

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
negative regulation of mitochondrial membrane permeability	2
acyl-CoA hydrolase activity	2
catalytic activity	2
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
negative regulation of organelle organization	1
mitochondrial outer membrane permeabilization	1
regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	1
negative regulation of apoptotic signaling pathway	1
apoptotic process	1
regulation of mitochondrial membrane permeability involved in apoptotic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
nucleic acid binding	1
acetyl-CoA C-acyltransferase activity	1
C-acetyltransferase activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
transferase activity	1
acyltransferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
nucleoplasm	1
intracellular membraneless organelle	1
microtubule organizing center	1
cilium	1

Protein interactions and networks

STRING

2862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACAA2	HADHA	P40939	962
ACAA2	ECHS1	P30084	927
ACAA2	EHHADH	Q08426	883
ACAA2	ACOX1	Q15067	814
ACAA2	HMGCS2	P54868	795
ACAA2	CPT1A	P50416	780
ACAA2	HMGCS1	Q01581	779
ACAA2	ACOX3	O15254	772
ACAA2	ACADM	P11310	760
ACAA2	ACSL1	P33121	760
ACAA2	CPT2	P23786	734
ACAA2	ACADVL	P49748	694
ACAA2	HADH	Q16836	677
ACAA2	ACADS	P16219	672
ACAA2	PEX13	Q92968	671

IntAct

62 interactions, top by confidence:

A	B	Type	Score
ACAA2	LARS2	psi-mi:“MI:0914”(association)	0.530
ACAA2	MGME1	psi-mi:“MI:0914”(association)	0.530
	ACAA2	psi-mi:“MI:0915”(physical association)	0.480
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
HSPB2	ACAA2	psi-mi:“MI:0915”(physical association)	0.370
ARMC6		psi-mi:“MI:0914”(association)	0.350
FASTKD3	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
NT5C3A	VWA8	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	NAP1L4	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
CIAO1	SOX1	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
CDK18	COL1A1	psi-mi:“MI:0914”(association)	0.350
MYLK2	MYO1B	psi-mi:“MI:0914”(association)	0.350
	KRAS	psi-mi:“MI:0914”(association)	0.350
UGT2B7	ACTN4	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
RMC1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
RMC1	ARID1A	psi-mi:“MI:0914”(association)	0.350
TMIGD1	DDX39A	psi-mi:“MI:0914”(association)	0.350
CLIP1	RGPD3	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
ACAA2	DBT	psi-mi:“MI:0914”(association)	0.350

BioGRID (206): MTIF2 (Affinity Capture-MS), PREPL (Affinity Capture-MS), TRMT61B (Affinity Capture-MS), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (Co-fractionation), ACAA2 (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

4 interactions.

A	Effect	B	Mechanism
ACAA2	“down-regulates quantity”	acetyl-CoA(4-)	“chemical modification”
ACAA2	“down-regulates quantity”	acyl-CoA(4-)	“chemical modification”
ACAA2	“up-regulates quantity”	“3-oxo-fatty acyl-CoA”	“chemical modification”
ACAA2	“up-regulates quantity”	“coenzyme A(4-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	0
Uncertain significance	65
Likely benign	3
Benign	6

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
147762	GRCh38/hg38 18q12.2-22.1(chr18:38794728-65632804)x3	Pathogenic
154074	GRCh38/hg38 18q12.3-23(chr18:40367455-80256240)x3	Pathogenic
3391862	GRCh37/hg19 18q11.2-23(chr18:19309942-78014123)x3	Pathogenic
441661	GRCh37/hg19 18q21.1-23(chr18:46177798-78014123)x1	Pathogenic
441853	GRCh37/hg19 18q12.2-23(chr18:33417216-78014123)x3	Pathogenic
442528	GRCh37/hg19 18q21.1-23(chr18:43776770-78014123)x3	Pathogenic
443117	GRCh37/hg19 18q12.3-23(chr18:42930373-78014123)x3	Pathogenic
443196	GRCh37/hg19 18q12.1-23(chr18:31879854-78014123)x3	Pathogenic
564571	GRCh37/hg19 18q21.1-23(chr18:46942427-78014123)x1	Pathogenic
686410	GRCh37/hg19 18q21.1-21.33(chr18:45621155-61416536)x3	Pathogenic
816014	GRCh37/hg19 18q11.2-21.2(chr18:20689919-49455212)x3	Pathogenic

SpliceAI

1574 predictions. Top by Δscore:

Variant	Effect	Δscore
18:49783929:CGC:C	acceptor_gain	1.0000
18:49783932:C:CC	acceptor_gain	1.0000
18:49787286:CTTA:C	donor_loss	1.0000
18:49787287:TTACC:T	donor_loss	1.0000
18:49787288:TAC:T	donor_loss	1.0000
18:49787289:A:AC	donor_gain	1.0000
18:49787289:ACCTC:A	donor_loss	1.0000
18:49787290:C:CC	donor_gain	1.0000
18:49787290:CCT:C	donor_gain	1.0000
18:49787360:ACCTA:A	acceptor_loss	1.0000
18:49787361:CCT:C	acceptor_loss	1.0000
18:49787362:C:CA	acceptor_loss	1.0000
18:49787363:T:C	acceptor_loss	1.0000
18:49791599:CCT:C	acceptor_gain	1.0000
18:49791601:T:C	acceptor_gain	1.0000
18:49792161:C:A	donor_gain	1.0000
18:49792323:ATTAG:A	acceptor_gain	1.0000
18:49792324:TTAG:T	acceptor_gain	1.0000
18:49792325:TAG:T	acceptor_gain	1.0000
18:49792326:AG:A	acceptor_gain	1.0000
18:49792328:C:CA	acceptor_loss	1.0000
18:49792328:C:CC	acceptor_gain	1.0000
18:49792329:T:G	acceptor_loss	1.0000
18:49794265:T:A	donor_gain	1.0000
18:49794274:ACTC:A	donor_loss	1.0000
18:49794275:CTCA:C	donor_loss	1.0000
18:49794277:CA:C	donor_loss	1.0000
18:49794278:A:AC	donor_gain	1.0000
18:49794278:AC:A	donor_gain	1.0000
18:49794278:ACCAG:A	donor_gain	1.0000

AlphaMissense

2562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:49785337:A:C	F323L	0.999
18:49785337:A:T	F323L	0.999
18:49785339:A:G	F323L	0.999
18:49797566:C:A	R71M	0.997
18:49783873:C:G	A390P	0.996
18:49794421:C:G	D146H	0.995
18:49795825:G:C	S123R	0.995
18:49795825:G:T	S123R	0.995
18:49795827:T:G	S123R	0.995
18:49797473:C:T	G102E	0.995
18:49797500:C:T	G93D	0.995
18:49792188:G:C	F239L	0.994
18:49792188:G:T	F239L	0.994
18:49792190:A:G	F239L	0.994
18:49797566:C:G	R71T	0.994
18:49783884:C:A	G386V	0.993
18:49783895:G:C	C382W	0.993
18:49791476:C:G	G293R	0.993
18:49791477:C:A	M292I	0.993
18:49791477:C:G	M292I	0.993
18:49791477:C:T	M292I	0.993
18:49791586:C:T	G256D	0.993
18:49791590:C:G	D255H	0.993
18:49802829:C:G	R14P	0.993
18:49783872:G:T	A390D	0.992
18:49783884:C:T	G386D	0.992
18:49785233:C:T	G358E	0.992
18:49785250:G:C	H352Q	0.992
18:49785250:G:T	H352Q	0.992
18:49785280:A:C	N342K	0.992

dbSNP variants (sampled 300 via entrez): RS1000049115 (18:49801380 C>A,T), RS1000106961 (18:49807584 C>A,T), RS1000116033 (18:49802710 C>T), RS1000216044 (18:49806615 C>G), RS1000221073 (18:49807256 A>G), RS1000287325 (18:49813007 A>T), RS1000329753 (18:49800889 A>AT), RS1000520708 (18:49808045 C>T), RS1000696113 (18:49811355 T>C), RS1000812105 (18:49812820 C>T), RS1000887716 (18:49796725 G>A), RS1001070099 (18:49802224 G>A,C), RS1001122807 (18:49800866 C>A,G,T), RS1001162344 (18:49789459 G>A,C), RS1001175040 (18:49801028 G>A)

Disease associations

OMIM: gene MIM:604770 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST000133_4	HDL cholesterol	2.000000e-07
GCST002579_23	Heschl’s gyrus morphology	2.000000e-06
GCST003801_3	Response to selective serotonin reuptake inhibitors in depression	9.000000e-07
GCST005446_36	Total cholesterol levels in HDL	5.000000e-07
GCST005455_12	Mean diameter of HDL particles	1.000000e-09
GCST005497_9	Large HDL particle concentration	3.000000e-10
GCST005499_16	Phospholipid levels in large HDL	2.000000e-10
GCST005500_2	Total cholesterol levels in large HDL	2.000000e-08
GCST005501_2	Cholesterol ester levels in very large HDL	1.000000e-08
GCST005503_11	Medium HDL particle concentration	7.000000e-10
GCST005504_2	Phospholipid levels in medium HDL	2.000000e-09
GCST005507_3	Free cholesterol levels in medium HDL	1.000000e-08
GCST005513_3	Apolipoprotein A1 levels	2.000000e-10
GCST006186_2	Systolic blood pressure x smoking status (current vs non-current) interaction (1df test)	8.000000e-06
GCST006195_92	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-08
GCST008070_121	HDL cholesterol levels	1.000000e-17
GCST008070_48	HDL cholesterol levels	1.000000e-45
GCST008070_70	HDL cholesterol levels	6.000000e-32
GCST008075_140	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-106
GCST008075_207	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-26
GCST008075_5	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-79
GCST008078_129	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-07
GCST008079_131	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-08
GCST008084_106	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-92
GCST008084_146	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-121
GCST008084_70	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-28
GCST008085_123	HDL cholesterol levels in current drinkers	2.000000e-43
GCST008085_44	HDL cholesterol levels in current drinkers	2.000000e-58
GCST008085_77	HDL cholesterol levels in current drinkers	1.000000e-17
GCST008086_6	LDL cholesterol levels in current drinkers	2.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0008589	esterified cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0010596	monocyte chemotactic protein 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066310 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.50	Kd	3.175	nM	CHEMBL5653589
8.50	ED50	3.175	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147775: Binding affinity to human ACAA2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0032	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	4
perfluorooctanoic acid	increases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	increases abundance, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
quinone	decreases expression	1
lasiocarpine	decreases expression	1
chlortoluron	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
beta-lapachone	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
ciglitazone	affects binding, increases expression	1
flavone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
K 7174	decreases expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
obeticholic acid	increases expression	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650817	Binding	Binding affinity to human ACAA2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1P7	HAP1 ACAA2 (-) 1	Cancer cell line	Male
CVCL_E1P8	HAP1 ACAA2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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