ACAA1

Summary

ACAA1 (acetyl-CoA acyltransferase 1, HGNC:82) is a protein-coding gene on chromosome 3p22.2, encoding 3-ketoacyl-CoA thiolase, peroxisomal (P09110). Responsible for the thiolytic cleavage of straight chain 3-keto fatty acyl-CoAs (3-oxoacyl-CoAs).

This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 30 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 90 total — 2 pathogenic
• MANE Select transcript: NM_001607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:82
Approved symbol	ACAA1
Name	acetyl-CoA acyltransferase 1
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	Lnc-Myd88
Ensembl gene	ENSG00000060971
Ensembl biotype	protein_coding
OMIM	604054
Entrez	30

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 17 protein_coding, 6 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000301810, ENST00000333167, ENST00000411549, ENST00000418880, ENST00000421218, ENST00000440176, ENST00000447223, ENST00000450296, ENST00000451419, ENST00000452171, ENST00000460424, ENST00000465181, ENST00000469559, ENST00000469600, ENST00000480865, ENST00000484284, ENST00000489559, ENST00000625927, ENST00000896221, ENST00000896222, ENST00000896223, ENST00000896224, ENST00000896225, ENST00000896226, ENST00000896227, ENST00000896228, ENST00000896229, ENST00000955504, ENST00000955505, ENST00000955506

RefSeq mRNA: 2 — MANE Select: NM_001607 NM_001130410, NM_001607

CCDS: CCDS2673, CCDS46794

Canonical transcript exons

ENST00000333167 — 12 exons

Exon	Start	End
ENSE00001702141	38126162	38126341
ENSE00001799097	38126510	38126700
ENSE00001927555	38136865	38137127
ENSE00003473889	38125826	38125881
ENSE00003533521	38125565	38125710
ENSE00003535054	38131926	38132005
ENSE00003543469	38127786	38127866
ENSE00003550112	38131596	38131638
ENSE00003569978	38133952	38134009
ENSE00003576672	38129290	38129388
ENSE00003678471	38136592	38136685
ENSE00003849359	38122715	38123122

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.1235 / max 386.7451, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41707	29.5208	1820
41709	0.7065	400
41708	0.6282	317
41706	0.2680	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.57	gold quality
right lobe of liver	UBERON:0001114	99.32	gold quality
mucosa of transverse colon	UBERON:0004991	99.07	gold quality
liver	UBERON:0002107	98.82	gold quality
duodenum	UBERON:0002114	98.76	gold quality
nephron tubule	UBERON:0001231	98.64	gold quality
adult mammalian kidney	UBERON:0000082	98.50	gold quality
renal medulla	UBERON:0000362	98.32	gold quality
apex of heart	UBERON:0002098	98.27	gold quality
granulocyte	CL:0000094	98.06	gold quality
kidney epithelium	UBERON:0004819	97.81	gold quality
body of pancreas	UBERON:0001150	97.39	gold quality
lower esophagus mucosa	UBERON:0035834	97.39	gold quality
metanephros cortex	UBERON:0010533	97.35	gold quality
cortex of kidney	UBERON:0001225	97.31	gold quality
renal glomerulus	UBERON:0000074	97.24	gold quality
right adrenal gland cortex	UBERON:0035827	97.21	gold quality
jejunum	UBERON:0002115	97.16	gold quality
esophagus squamous epithelium	UBERON:0006920	97.14	gold quality
parotid gland	UBERON:0001831	97.06	gold quality
metanephric glomerulus	UBERON:0004736	97.05	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.04	gold quality
right uterine tube	UBERON:0001302	97.03	gold quality
epithelium of esophagus	UBERON:0001976	97.01	gold quality
heart left ventricle	UBERON:0002084	97.01	gold quality
kidney	UBERON:0002113	97.01	gold quality
right adrenal gland	UBERON:0001233	96.94	gold quality
cardiac ventricle	UBERON:0002082	96.94	gold quality
spleen	UBERON:0002106	96.93	gold quality
adrenal cortex	UBERON:0001235	96.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	29.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting ACAA1, 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-512-3P	99.97	67.35	1049
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-2278	97.30	66.19	1130

Literature-anchored findings (GeneRIF, showing 7)

• To unravel the biochemical and functional relationship between Rnl1, Rnl2, and Dnl, a systematic analysis of their substrate specificity was performed using recombinant proteins (PMID:16671895)
• Kinetic characterization of single strand break ligation in duplex DNA by T4 DNA ligase (PMID:22027837)
• The alpha-helical DNA-binding domain (DBD) of T4 DNA ligase exhibits structural homology to the core DNA-binding helices of the larger DBDs from eukaryotic and archaeal DNA ligases. (PMID:30169742)
• Findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1. (PMID:22151743)
• A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease, impairs lysosomal function, and facilitates amyloid-beta pathology and cognitive decline. (PMID:34465723)
• Inhibition of ACAA1 Restrains Proliferation and Potentiates the Response to CDK4/6 Inhibitors in Triple-Negative Breast Cancer. (PMID:37129951)
• [Clinical phenotypic and genotypic analysis of 5 pediatric patients with beta-ketothiolase deficiency]. (PMID:38154980)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acaa1	ENSDARG00000004687
mus_musculus	Acaa1b	ENSMUSG00000010651
mus_musculus	Acaa1a	ENSMUSG00000036138
rattus_norvegicus	Acaa1a	ENSRNOG00000032908
rattus_norvegicus	Acaa1b	ENSRNOG00000067803

Paralogs (4): ACAT1 (ENSG00000075239), ACAT2 (ENSG00000120437), HADHB (ENSG00000138029), ACAA2 (ENSG00000167315)

Protein

Protein identifiers

3-ketoacyl-CoA thiolase, peroxisomal — P09110 (reviewed: P09110)

Alternative names: Acetyl-CoA C-myristoyltransferase, Acetyl-CoA acyltransferase, Beta-ketothiolase, Peroxisomal 3-oxoacyl-CoA thiolase

All UniProt accessions (9): P09110, A0A024R2M6, A0A140VJX0, B4DVF4, C9JDE9, F2Z2Q6, F2Z3P7, H0Y4D4, H7C131

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for the thiolytic cleavage of straight chain 3-keto fatty acyl-CoAs (3-oxoacyl-CoAs). Plays an important role in fatty acid peroxisomal beta-oxidation. Catalyzes the cleavage of short, medium, long, and very long straight chain 3-oxoacyl-CoAs.

Subunit / interactions. Homodimer (Ref.16). Interacts (via PTS2-type peroxisomal targeting signal region) with PEX7; leading to its translocation into peroxisomes.

Subcellular location. Peroxisome.

Domain organisation. The PTS2-type peroxisomal targeting signal, which mediates interaction with PEX7 and localization to peroxisomes, is cleaved following import into peroxisomes.

Induction. Peroxisomal thiolase is markedly induced (at the level of transcription) by various hypolipidemic compounds in parallel with the other two enzymes of the peroxisomal beta-oxidation system.

Pathway. Lipid metabolism; peroxisomal fatty acid beta-oxidation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P09110-1	1	yes
P09110-2	2

RefSeq proteins (2): NP_001123882, NP_001598* (*=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
IPR050215	FADA-like	Family

Pfam: PF00108, PF02803

Catalyzed reactions (Rhea), 6 shown:

• tetradecanoyl-CoA + acetyl-CoA = 3-oxohexadecanoyl-CoA + CoA (RHEA:18161)
• 2 acetyl-CoA = acetoacetyl-CoA + CoA (RHEA:21036)
• an acyl-CoA + acetyl-CoA = a 3-oxoacyl-CoA + CoA (RHEA:21564)
• hexanoyl-CoA + acetyl-CoA = 3-oxooctanoyl-CoA + CoA (RHEA:31203)
• 3-oxo-(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + acetyl-CoA (RHEA:39131)
• 3-oxohexadecanedioyl-CoA + CoA = tetradecanedioyl-CoA + acetyl-CoA (RHEA:40343)

UniProt features (58 total): helix 20, strand 13, mutagenesis site 7, turn 6, active site 3, sequence variant 2, modified residue 2, splice variant 2, transit peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9OK4	X-RAY DIFFRACTION	2.28
2IIK	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09110-F1	93.93	0.90

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): 123 (acyl-thioester intermediate); 377 (proton acceptor); 408 (proton acceptor)

Post-translational modifications (2): 59, 60

Mutagenesis-validated functional residues (7):

Position	Phenotype
5	does not affect localization to peroxisomes.
6	abolished localization to peroxisomes.
6	does not affect localization to peroxisomes.
7	abolished localization to peroxisomes.
8	does not affect localization to peroxisomes.
9	does not affect localization to peroxisomes.
10	in s3e mutant; abolished localization to peroxisomes.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism
R-HSA-390247	Beta-oxidation of very long chain fatty acids
R-HSA-6798695	Neutrophil degranulation
R-HSA-9033241	Peroxisomal protein import
R-HSA-9033500	TYSND1 cleaves peroxisomal proteins
R-HSA-1430728	Metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2046104	alpha-linolenic (omega3) and linoleic (omega6) acid metabolism
R-HSA-390918	Peroxisomal lipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism
R-HSA-9609507	Protein localization

MSigDB gene sets: 251 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, MODULE_151, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS

GO Biological Process (8): very long-chain fatty acid metabolic process (GO:0000038), fatty acid beta-oxidation (GO:0006635), bile acid metabolic process (GO:0008206), phenylacetate catabolic process (GO:0010124), fatty acid beta-oxidation using acyl-CoA oxidase (GO:0033540), alpha-linolenic acid metabolic process (GO:0036109), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (10): acetyl-CoA C-acetyltransferase activity (GO:0003985), acetyl-CoA C-acyltransferase activity (GO:0003988), acetate CoA-transferase activity (GO:0008775), acetyl-CoA C-myristoyltransferase activity (GO:0050633), long-chain fatty acyl-CoA oxidase activity (GO:0120524), protein binding (GO:0005515), obsolete palmitoyl-CoA oxidase activity (GO:0016401), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (7): extracellular region (GO:0005576), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), membrane (GO:0016020), specific granule lumen (GO:0035580), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Fatty acid metabolism	2
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1
Peroxisomal lipid metabolism	1
Innate Immune System	1
Protein localization	1
Peroxisomal protein import	1
Immune System	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
monocarboxylic acid metabolic process	2
fatty acid metabolic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
steroid metabolic process	1
xenobiotic catabolic process	1
benzene-containing compound metabolic process	1
monocarboxylic acid catabolic process	1
fatty acid beta-oxidation	1
long-chain fatty acid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
primary metabolic process	1
lipid metabolic process	1
acetyl-CoA C-acyltransferase activity	1
C-acetyltransferase activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
CoA-transferase activity	1
myristoyltransferase activity	1
acyl-CoA oxidase activity	1
binding	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
microbody	1
peroxisome	1
microbody lumen	1
cytoplasm	1
secretory granule lumen	1
specific granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACAA1	ACOX1	Q15067	946
ACAA1	ECHS1	P30084	940
ACAA1	EHHADH	Q08426	939
ACAA1	HSD17B4	P51659	920
ACAA1	ACOX3	O15254	918
ACAA1	HADHA	P40939	893
ACAA1	GNPAT	O15228	879
ACAA1	PEX5	P50542	855
ACAA1	TYSND1	Q2T9J0	824
ACAA1	ACOX2	Q99424	809
ACAA1	PEX13	Q92968	785
ACAA1	PEX10	O60683	783
ACAA1	TECR	Q9NZ01	749
ACAA1	ACADS	P16219	697
ACAA1	ACADSB	P45954	685

IntAct

47 interactions, top by confidence:

A	B	Type	Score
ACAA1	TFCP2	psi-mi:“MI:0915”(physical association)	0.560
ACAA1	FEM1A	psi-mi:“MI:0915”(physical association)	0.560
ACAA1	PEX7	psi-mi:“MI:0914”(association)	0.530
PEX39	PEX7	psi-mi:“MI:0914”(association)	0.530
MRPL42	GATC	psi-mi:“MI:0914”(association)	0.530
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
BMP2K	ACAA1	psi-mi:“MI:0915”(physical association)	0.490
PPP1R7	ACAA1	psi-mi:“MI:0915”(physical association)	0.400
ACAA1	TXNDC11	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PDHA1		psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
KHDRBS2	SUPT5H	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
HTRA2	VWA8	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
UGT2B7	ACTN4	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
GTF2E2	STX7	psi-mi:“MI:0914”(association)	0.350
TFPT	KRBA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (104): PEX7 (Affinity Capture-MS), MTHFD2 (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), C6orf226 (Affinity Capture-MS), PEX5 (Affinity Capture-MS), CAT (Co-fractionation), CDK12 (Co-fractionation), ACAA1 (Affinity Capture-MS), ACAA1 (Affinity Capture-MS), PEX7 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), MTHFD2 (Affinity Capture-MS), ACAA1 (Affinity Capture-MS), ACAA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PH52, A0KEL0, A0KR49, A1S1I7, A1TZR8, A3Q8U3, A4STF3, A4WFX5, A6TGM3, A6VVM8, B0XMC1, B0YA65, B5FEW7, I1RMA2, I1RY81, O32177, P07871, P09110, P10551, P13437, P14611, P41338, P42765, Q04677, Q05493, Q0HPB8, Q0I0T4, Q12598, Q15ZF4, Q22100, Q3IJ24, Q3K9D9, Q489W4, Q4KFC3, Q4WCL5, Q4WLA8, Q5E8X7, Q5QXH8, Q6L8K7, Q86AD9

Diamond homologs: A0A1D8PH52, A0KEL0, A0R1Y7, A1S1I7, A1TZR8, A6WH99, A7MQM5, B0XMC1, B0YA65, B5FEW7, B6EGU1, C6DI66, C8YNG6, I1RMA2, I1RY81, O32177, P07097, P07871, P09110, P0C7L2, P0C7L3, P10551, P13437, P14611, P17764, P21775, P24752, P33290, P33291, P41338, P42765, P44873, P45359, P45363, P45369, P45855, P46707, P50174, P54810, P66927

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	62
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
145586	GRCh38/hg38 3p22.3-22.1(chr3:33728406-40662451)x3	Pathogenic
153415	GRCh38/hg38 3p26.3-22.1(chr3:53308-41381521)x3	Pathogenic

SpliceAI

4990 predictions. Top by Δscore:

Variant	Effect	Δscore
3:38107574:C:CA	acceptor_gain	1.0000
3:38107576:T:TA	acceptor_gain	1.0000
3:38107581:CAGCT:C	acceptor_loss	1.0000
3:38107582:A:AG	acceptor_gain	1.0000
3:38107583:G:GG	acceptor_gain	1.0000
3:38107583:GCT:G	acceptor_gain	1.0000
3:38107583:GCTA:G	acceptor_gain	1.0000
3:38107583:GCTAC:G	acceptor_gain	1.0000
3:38107735:AAGGT:A	donor_loss	1.0000
3:38107738:G:A	donor_loss	1.0000
3:38107739:T:G	donor_loss	1.0000
3:38111667:A:AG	acceptor_gain	1.0000
3:38111667:ACTT:A	acceptor_gain	1.0000
3:38111670:T:A	acceptor_gain	1.0000
3:38111673:A:AG	acceptor_gain	1.0000
3:38111674:A:G	acceptor_gain	1.0000
3:38111675:A:G	acceptor_gain	1.0000
3:38111676:G:GG	acceptor_gain	1.0000
3:38111743:GCTGG:G	donor_gain	1.0000
3:38112360:CGGTA:C	donor_loss	1.0000
3:38112361:GGTA:G	donor_loss	1.0000
3:38112363:T:G	donor_loss	1.0000
3:38114978:TCCA:T	acceptor_loss	1.0000
3:38114979:CCA:C	acceptor_loss	1.0000
3:38114980:CA:C	acceptor_loss	1.0000
3:38114981:A:AG	acceptor_gain	1.0000
3:38114981:AGGTT:A	acceptor_loss	1.0000
3:38114982:G:A	acceptor_loss	1.0000
3:38114982:G:GG	acceptor_gain	1.0000
3:38114982:GGTTC:G	acceptor_gain	1.0000

AlphaMissense

2730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:38125835:A:C	F348L	0.999
3:38125835:A:T	F348L	0.999
3:38125837:A:G	F348L	0.999
3:38125633:G:C	H377Q	0.998
3:38125633:G:T	H377Q	0.998
3:38125634:T:C	H377R	0.998
3:38125635:G:C	H377D	0.998
3:38126322:A:C	S279R	0.998
3:38126322:A:T	S279R	0.998
3:38126324:T:G	S279R	0.998
3:38127858:G:A	S185F	0.998
3:38131962:A:G	C123R	0.998
3:38125637:C:T	G376E	0.997
3:38125829:G:C	S350R	0.997
3:38125829:G:T	S350R	0.997
3:38125831:T:G	S350R	0.997
3:38126318:C:A	G281W	0.997
3:38126331:G:C	S276R	0.997
3:38126331:G:T	S276R	0.997
3:38126333:T:G	S276R	0.997
3:38126535:G:C	F264L	0.997
3:38126535:G:T	F264L	0.997
3:38126537:A:G	F264L	0.997
3:38126594:C:G	D245H	0.997
3:38131944:C:G	A129P	0.997
3:38131958:G:C	S124W	0.997
3:38131960:A:C	C123W	0.997
3:38131969:A:C	N120K	0.997
3:38131969:A:T	N120K	0.997
3:38123069:A:T	V418D	0.996

dbSNP variants (sampled 300 via entrez): RS1000135952 (3:38134646 T>C), RS1000588245 (3:38125733 C>T), RS1000619534 (3:38126035 G>A), RS1001139718 (3:38132369 TC>T,TCC), RS1001593411 (3:38128668 T>G), RS1002187041 (3:38122882 GTCA>G), RS1002356645 (3:38133195 A>G), RS1002534732 (3:38134132 C>T), RS1002598261 (3:38129065 G>A), RS1003185241 (3:38130144 A>G), RS1003257813 (3:38129925 G>A), RS1003464373 (3:38123466 G>A,T), RS1003545590 (3:38136994 C>A,G,T), RS1003589198 (3:38124111 A>G), RS1003779677 (3:38123907 T>TGAGGCA)

Disease associations

OMIM: gene MIM:604054 | disease phenotypes: MIM:601144

GenCC curated gene-disease

Mondo (1): Brugada syndrome (MONDO:0015263)

Orphanet (1): Brugada syndrome (Orphanet:130)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003875_38	Gut microbiota (bacterial taxa)	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
Cyclosporine	decreases expression, decreases methylation	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cisplatin	affects cotreatment, increases expression	2
Diethylhexyl Phthalate	increases abundance, increases methylation, increases expression, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Aflatoxin B1	decreases expression, affects expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
chlortoluron	decreases expression	1
deoxynivalenol	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
doxifluridine	increases response to substance	1
ochratoxin A	decreases expression	1
1-UFT protocol	increases response to substance	1
ciglitazone	affects binding, increases expression	1
S 1 (combination)	increases response to substance	1
cyproconazole	decreases expression	1
K 7174	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, increases expression	1
obeticholic acid	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D2HR	Abcam Raji ACAA1 KO	Cancer cell line	Male
CVCL_UQ01	Abcam Jurkat ACAA1 KO	Cancer cell line	Male
CVCL_WQ85	Abcam K-562 ACAA1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT02933437	PHASE2	UNKNOWN	The Response To Ajmaline Provocation in Healthy Subjects
NCT07146880	PHASE2	NOT_YET_RECRUITING	Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT02014961	Not specified	UNKNOWN	Worm Study: Modifier Genes in Sudden Cardiac Death
NCT02052765	Not specified	COMPLETED	AnalyST & Brugada Syndrome - Feasibility Study
NCT02302274	Not specified	COMPLETED	Diagnostic Value and Safety of Flecainide Infusion Test in Brugada Syndrome
NCT02344277	Not specified	COMPLETED	Evaluation of Subcutaneous Implantable Cardiac Defibrillator in Brugada Patients
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02641431	Not specified	COMPLETED	Epicardial Ablation in Brugada Syndrome
NCT02704416	Not specified	COMPLETED	Ablation in Brugada Syndrome for the Prevention of VF
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03435393	Not specified	UNKNOWN	Ripple Mapping for Epicardial Mapping of Brugada Syndrome
NCT03485508	Not specified	UNKNOWN	The Brugada Syndrome: a Follow-up Study
NCT03491475	Not specified	UNKNOWN	Echocardiography During Ajmaline Test
NCT03524079	Not specified	COMPLETED	Right Ventricle Morphology and Hemodynamics in BrS
NCT03764592	Not specified	COMPLETED	VF Mapping in Brugada and Early Repolarization Syndromes
NCT03775954	Not specified	RECRUITING	Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
NCT03992677	Not specified	COMPLETED	Feasibility of Improving Risk Stratification in Brugada Syndrome
NCT04124237	Not specified	COMPLETED	Long Term Monitoring for Risk of Sudden Death
NCT04232787	Not specified	UNKNOWN	Southeast Asian Brugada Syndrome Cohort
NCT04257994	Not specified	RECRUITING	Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders
NCT04420078	Not specified	COMPLETED	Brugada Ablation of VF Substrate Ongoing MultiCenter Registry
NCT04580992	Not specified	UNKNOWN	Defining the Electrocardiographic Effect of Propofol on the Ajmaline Provocation Drug Challenge: A Prospective Trial
NCT04650009	Not specified	COMPLETED	Physical Activity in Children With Inherited Cardiac Diseases
NCT04712136	Not specified	COMPLETED	Healthy-related Quality of Life and Physical Activity of Children With Cardiac Malformations
NCT04808193	Not specified	UNKNOWN	European Perioperative Brugada Survey
NCT05048602	Not specified	UNKNOWN	Drug-induced Brugada Syndrome Research Database
NCT05274646	Not specified	COMPLETED	Impact on Risk Stratification of Overlap Syndrome Phenotype in Patients With E1784K Mutation in SCN5A
NCT05283759	Not specified	RECRUITING	UZ Brussel HRMC Registry of Brugada Syndrome
NCT05521451	Not specified	RECRUITING	Clinical Cohort Study - TRUST
NCT05643209	Not specified	RECRUITING	Brugada Syndrome Substrate Characterization and Ablation
NCT05685134	Not specified	COMPLETED	Epicardial Radiofrequency Catheter Ablation in Patients With Brugada Syndrome
NCT06376552	Not specified	COMPLETED	Artificial Intelligence for the Prioritization of Genetic Background in Brugada Syndrome
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT06567639	Not specified	COMPLETED	High Density Mapping in Brugada Syndrome
NCT06647927	Not specified	RECRUITING	GenLab: Unveiling the Genetic Landscape of Brugada Syndrome: Novel Biomarker Discovery for Precise Diagnosis
NCT06653504	Not specified	COMPLETED	The Conus Brugada Syndrome Study