ACOX1

Summary

ACOX1 (acyl-CoA oxidase 1, HGNC:119) is a protein-coding gene on chromosome 17q25.1, encoding Peroxisomal acyl-coenzyme A oxidase 1 (Q15067). Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids.

The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 51 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Mitchell syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 957 total — 43 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 65
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004035

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:119
Approved symbol	ACOX1
Name	acyl-CoA oxidase 1
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	PALMCOX
Ensembl gene	ENSG00000161533
Ensembl biotype	protein_coding
OMIM	609751
Entrez	51

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000293217, ENST00000301608, ENST00000572047, ENST00000573078, ENST00000576743, ENST00000587927, ENST00000588176, ENST00000588968, ENST00000589301, ENST00000589744, ENST00000591857, ENST00000591963, ENST00000592329, ENST00000911074, ENST00000911075, ENST00000911076, ENST00000911077, ENST00000911078, ENST00000949477, ENST00000949478, ENST00000949479, ENST00000949480

RefSeq mRNA: 3 — MANE Select: NM_004035 NM_001185039, NM_004035, NM_007292

CCDS: CCDS11734, CCDS11735

Canonical transcript exons

ENST00000293217 — 14 exons

Exon	Start	End
ENSE00001419361	75978965	75979166
ENSE00002864661	75941507	75946795
ENSE00003494284	75955566	75955681
ENSE00003499372	75957459	75957566
ENSE00003549935	75948251	75948457
ENSE00003563898	75951415	75951577
ENSE00003571313	75949718	75949897
ENSE00003581502	75955828	75955947
ENSE00003597322	75978534	75978693
ENSE00003601591	75949217	75949360
ENSE00003610768	75950774	75950964
ENSE00003619178	75960215	75960375
ENSE00003620890	75953451	75953620
ENSE00003683677	75949495	75949600

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.4601 / max 344.6896, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168148	27.4636	1823
168150	3.5954	1549
168147	2.6170	1309
168145	0.4029	164
168149	0.3812	179

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.16	gold quality
buccal mucosa cell	CL:0002336	97.25	gold quality
duodenum	UBERON:0002114	96.59	gold quality
esophagus squamous epithelium	UBERON:0006920	96.08	gold quality
mucosa of transverse colon	UBERON:0004991	95.19	gold quality
liver	UBERON:0002107	95.15	gold quality
right lobe of liver	UBERON:0001114	94.57	gold quality
epithelium of esophagus	UBERON:0001976	94.47	gold quality
colonic mucosa	UBERON:0000317	93.09	gold quality
medial globus pallidus	UBERON:0002477	92.14	gold quality
jejunum	UBERON:0002115	92.13	gold quality
oral cavity	UBERON:0000167	92.10	gold quality
ileal mucosa	UBERON:0000331	92.09	gold quality
rectum	UBERON:0001052	92.01	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.97	gold quality
colonic epithelium	UBERON:0000397	91.81	gold quality
adrenal tissue	UBERON:0018303	91.62	gold quality
blood	UBERON:0000178	91.57	gold quality
lower esophagus mucosa	UBERON:0035834	91.54	gold quality
islet of Langerhans	UBERON:0000006	91.21	gold quality
globus pallidus	UBERON:0001875	91.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.15	gold quality
body of pancreas	UBERON:0001150	91.07	gold quality
esophagus mucosa	UBERON:0002469	91.05	gold quality
amniotic fluid	UBERON:0000173	90.87	gold quality
pancreas	UBERON:0001264	90.67	gold quality
gastrocnemius	UBERON:0001388	90.28	gold quality
upper leg skin	UBERON:0004262	90.14	gold quality
muscle of leg	UBERON:0001383	89.95	gold quality
adipose tissue	UBERON:0001013	89.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.16
E-GEOD-100618	no	223.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, MYC, NR1I3, NR2C2, PPARA, PPARD, RXRA, STAT3, STAT5A

miRNA regulators (miRDB)

188 targeting ACOX1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• Mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency. (PMID:17458872)
• report on two new patients with ACOX1 deficiency and mutational analyses (PMID:18536048)
• Data show that human ACOX1b isoform is more effective than the ACOX1a isoform in reversing the Acox1 null phenotype in the mouse. (PMID:20195242)
• ACOX1 and GNPAT silencing up-regulated ceramide galactosyltransferase (UGT8) mRNA expression, and down-regulated UDP-glucoseceramide glucosyltransferase (UGCG). (PMID:23933200)
• Because patients with AOx deficiency suffer from more severe symptoms than those with X-ALD, accumulation of VLC-PUFA and/or reduction of DHA may be associated with the severity of peroxisomal diseases. (PMID:24418004)
• In non-alcoholic fatty liver disease miR-222 promotes the accumulation of triglycerides by inhibiting ACOX1. (PMID:31126802)
• Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. (PMID:32169171)
• Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation. (PMID:32434419)
• Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency. (PMID:33234382)
• Association Between ACOX1 and NRF1 Gene Expression and Hepatitis B and C Virus Infections and Hepatocellular Carcinoma in Liver Transplant Patients (Shiraz, Iran). (PMID:34763625)
• Crystal structures of apo- and FAD-bound human peroxisomal acyl-CoA oxidase provide mechanistic basis explaining clinical observations. (PMID:35149097)
• MiR-103-3p promotes hepatic steatosis to aggravate nonalcoholic fatty liver disease by targeting of ACOX1. (PMID:35606603)
• ACOX1 Gain-of-Function Variant in Two German Pediatric Patients, in One Case Mimicking Autoimmune Inflammatory Disease. (PMID:37846133)
• ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia. (PMID:38057495)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	acox1	ENSDARG00000014727
mus_musculus	Acox1	ENSMUSG00000020777
rattus_norvegicus	Acox1	ENSRNOG00000008755
caenorhabditis_elegans	acox-1.1	WBGENE00008564
caenorhabditis_elegans	acox-1.2	WBGENE00008565
caenorhabditis_elegans	acox-1.3	WBGENE00008566
caenorhabditis_elegans	acox-1.4	WBGENE00008567
caenorhabditis_elegans		WBGENE00015894
caenorhabditis_elegans	acdh-1	WBGENE00016943
caenorhabditis_elegans		WBGENE00019406
caenorhabditis_elegans		WBGENE00020366

Paralogs (14): ACADVL (ENSG00000072778), ACOX3 (ENSG00000087008), GCDH (ENSG00000105607), ACAD10 (ENSG00000111271), ACADL (ENSG00000115361), ACADM (ENSG00000117054), ACADS (ENSG00000122971), IVD (ENSG00000128928), ACAD8 (ENSG00000151498), ACOXL (ENSG00000153093), ACOX2 (ENSG00000168306), ACAD9 (ENSG00000177646), ACADSB (ENSG00000196177), ACAD11 (ENSG00000240303)

Protein

Protein identifiers

Peroxisomal acyl-coenzyme A oxidase 1 — Q15067 (reviewed: Q15067)

Alternative names: Palmitoyl-CoA oxidase, Peroxisomal fatty acyl-CoA oxidase, Straight-chain acyl-CoA oxidase

All UniProt accessions (7): Q15067, I3L0T4, I3L2U4, I3L4S5, K7ELT1, K7ENF1, K7ESC7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids. Catalyzes the desaturation of fatty acyl-CoAs that have a saturated bond between C2 and C3 (2,3-saturated acyl-CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs), and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)). Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro. Is active against a much broader range of substrates and shows activity towards long-chain fatty acyl-CoAs.

Subunit / interactions. Homodimer. Interacts with LONP2.

Subcellular location. Peroxisome.

Tissue specificity. Widely expressed with highest levels of isoform 1 and isoform 2 detected in testis. Isoform 1 is expressed at higher levels than isoform 2 in liver and kidney while isoform 2 levels are higher in brain, lung, muscle, white adipose tissue and testis. Levels are almost equal in heart.

Disease relevance. Adrenoleukodystrophy, pseudoneonatal (Pseudo-NALD) [MIM:264470] A peroxisomal single-enzyme disorder of fatty acid beta-oxidation, resulting in clinical manifestations that remind neonatal adrenoleukodystrophy. Clinical features include intellectual disability, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty acids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning. The disease is caused by variants affecting the gene represented in this entry. Mitchell syndrome (MITCH) [MIM:618960] A disorder characterized by episodic demyelination, sensorimotor polyneuropathy, and sensorineural hearing loss. The gene represented in this entry is involved in disease pathogenesis.

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

Miscellaneous. Isoform 1 and isoform 2 can reverse the Acox1 null phenotype in mouse which is characterized by severe microvesicular hepatic steatosis, sustained activation of PPARA, spontaneous massive peroxisome proliferation and eventual development of hepatocellular carcinomas. Isoform 2 is more effective in reversal of the phenotype than isoform 1.

Similarity. Belongs to the acyl-CoA oxidase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15067-1	1, ACOX1a, SCOX-exon 3I	yes
Q15067-2	2, ACOX1b, SCOX-exon 3II
Q15067-3	3

RefSeq proteins (3): NP_001171968, NP_004026, NP_009223 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002655	Acyl-CoA_oxidase_C	Domain
IPR006091	AcylCoA_DH/ox_M	Domain
IPR009100	AcylCoA_DH/oxidase_NM_dom_sf	Homologous_superfamily
IPR012258	Acyl-CoA_oxidase	Family
IPR029320	Acyl-CoA_ox_N	Domain
IPR034171	ACO	Family
IPR036250	AcylCo_DH-like_C	Homologous_superfamily
IPR037069	AcylCoA_DH/ox_N_sf	Homologous_superfamily
IPR046373	Acyl-CoA_Oxase/DH_mid-dom_sf	Homologous_superfamily
IPR055060	ACOX_C_alpha1	Domain

Pfam: PF01756, PF02770, PF14749, PF22924

Enzyme classification (BRENDA):

• EC 1.3.3.6 — acyl-CoA oxidase (BRENDA: 43 organisms, 116 substrates, 43 inhibitors, 76 Km, 27 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PALMITOYL-COA	—	13
OCTANOYL-COA	0.042–0.087	11
DODECANOYL-COA	0.002–0.1	6
HEXANOYL-COA	0.006–0.092	5
DECANOYL-COA	0.002–0.024	4
MYRISTOYL-COA	0.0053–0.029	4
STEAROYL-COA	0.0044–0.034	4
LAUROYL-COA	0.013–0.027	3
BUTYRYL-COA	0.032–0.1319	2
CIS-3-DECENOYL-COA	0.044–0.054	2
CIS-3-HEXENOYL-COA	0.063–0.076	2
CIS-3-OCTENOYL-COA	0.054–0.057	2
LINOLEOYL-COA	0.0073–0.019	2
OLEOYL-COA	0.011–0.046	2
TRANS-3-DECENOYL-COA	0.056–0.064	2

Catalyzed reactions (Rhea), 12 shown:

• a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2 (RHEA:38959)
• octadecanoyl-CoA + O2 = (2E)-octadecenoyl-CoA + H2O2 (RHEA:38971)
• (6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + O2 = (2E,6Z,9Z,12Z,15Z,18Z,21Z)-tetracosaheptaenoyl-CoA + H2O2 (RHEA:39119)
• hexadecanoyl-CoA + O2 = (2E)-hexadecenoyl-CoA + H2O2 (RHEA:40167)
• dodecanoyl-CoA + O2 = (2E)-dodecenoyl-CoA + H2O2 (RHEA:40171)
• octanoyl-CoA + O2 = (2E)-octenoyl-CoA + H2O2 (RHEA:40175)
• decanoyl-CoA + O2 = (2E)-decenoyl-CoA + H2O2 (RHEA:40179)
• tetradecanoyl-CoA + O2 = (2E)-tetradecenoyl-CoA + H2O2 (RHEA:40183)
• hexadecanedioyl-CoA + O2 = (2E)-hexadecenedioyl-CoA + H2O2 (RHEA:40275)
• hexanoyl-CoA + O2 = (2E)-hexenoyl-CoA + H2O2 (RHEA:40311)
• glutaryl-CoA + O2 = (2E)-glutaconyl-CoA + H2O2 (RHEA:40315)
• tetracosanoyl-CoA + O2 = (2E)-tetracosenoyl-CoA + H2O2 (RHEA:40319)

UniProt features (60 total): modified residue 24, sequence conflict 14, sequence variant 12, chain 3, splice variant 2, binding site 2, short sequence motif 1, active site 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15067-F1	93.95	0.87

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 (2): 421 (proton acceptor); 468–469 (cleavage)

Ligand- & substrate-binding residues (2): 139; 178

Post-translational modifications (24): 90, 216, 241, 255, 267, 272, 349, 437, 437, 446, 446, 500, 504, 512, 512, 542, 637, 637, 643, 649 …

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9033241	Peroxisomal protein import
R-HSA-9033500	TYSND1 cleaves peroxisomal proteins
R-HSA-1989781	PPARA activates gene expression
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism
R-HSA-390247	Beta-oxidation of very long chain fatty acids
R-HSA-9609507	Protein localization

MSigDB gene sets: 447 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_FATTY_ACID_CATABOLIC_PROCESS, BROWNE_HCMV_INFECTION_6HR_DN, GRUETZMANN_PANCREATIC_CANCER_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_STEROL_HOMEOSTASIS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, ENK_UV_RESPONSE_KERATINOCYTE_UP, LUCAS_HNF4A_TARGETS_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (19): very long-chain fatty acid metabolic process (GO:0000038), generation of precursor metabolites and energy (GO:0006091), lipid metabolic process (GO:0006629), unsaturated fatty acid biosynthetic process (GO:0006636), prostaglandin metabolic process (GO:0006693), spermatogenesis (GO:0007283), fatty acid catabolic process (GO:0009062), peroxisome fission (GO:0016559), fatty acid oxidation (GO:0019395), fatty acid beta-oxidation using acyl-CoA oxidase (GO:0033540), alpha-linolenic acid metabolic process (GO:0036109), cholesterol homeostasis (GO:0042632), long-chain fatty acid biosynthetic process (GO:0042759), hydrogen peroxide biosynthetic process (GO:0050665), lipid homeostasis (GO:0055088), very long-chain fatty acid beta-oxidation (GO:0140493), fatty acid derivative biosynthetic process (GO:1901570), fatty acid metabolic process (GO:0006631), fatty acid beta-oxidation (GO:0006635)

GO Molecular Function (11): acyl-CoA oxidase activity (GO:0003997), fatty acid binding (GO:0005504), PDZ domain binding (GO:0030165), protein homodimerization activity (GO:0042803), flavin adenine dinucleotide binding (GO:0050660), FAD binding (GO:0071949), long-chain fatty acyl-CoA oxidase activity (GO:0120524), protein binding (GO:0005515), obsolete palmitoyl-CoA oxidase activity (GO:0016401), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (6): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Protein localization	1
Peroxisomal protein import	1
Regulation of lipid metabolism by PPARalpha	1
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1
Peroxisomal lipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid metabolic process	3
cellular anatomical structure	3
fatty acid biosynthetic process	2
unsaturated fatty acid metabolic process	2
long-chain fatty acid metabolic process	2
peroxisome	2
metabolic process	1
primary metabolic process	1
prostanoid metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
peroxisome organization	1
organelle fission	1
lipid oxidation	1
fatty acid beta-oxidation	1
olefinic compound metabolic process	1
sterol homeostasis	1
hydrogen peroxide metabolic process	1
reactive oxygen species biosynthetic process	1
chemical homeostasis	1
very long-chain fatty acid catabolic process	1
lipid biosynthetic process	1
fatty acid derivative metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
oxidoreductase activity, acting on the CH-CH group of donors, oxygen as acceptor	1
lipid binding	1
monocarboxylic acid binding	1
protein domain specific binding	1
identical protein binding	1
protein dimerization activity	1
nucleotide binding	1
anion binding	1
flavin adenine dinucleotide binding	1
acyl-CoA oxidase activity	1

Protein interactions and networks

STRING

3286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACOX1	HSD17B4	P51659	969
ACOX1	EHHADH	Q08426	968
ACOX1	ACAA1	P09110	946
ACOX1	HADHB	P55084	936
ACOX1	ECHS1	P30084	926
ACOX1	PPARA	Q07869	888
ACOX1	SREBF1	P36956	858
ACOX1	CPT1A	P50416	834
ACOX1	PEX5	P50542	832
ACOX1	ACAA2	P42765	814
ACOX1	SCD	O00767	806
ACOX1	ACADM	P11310	803
ACOX1	ABCD3	P28288	801
ACOX1	TYSND1	Q2T9J0	792
ACOX1	CPT2	P23786	789

IntAct

80 interactions, top by confidence:

A	B	Type	Score
CDKN2C	CDK4	psi-mi:“MI:0914”(association)	0.970
UBA5	GABARAPL2	psi-mi:“MI:0914”(association)	0.950
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
APBA2	APP	psi-mi:“MI:0914”(association)	0.690
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
APBA1	LIN7A	psi-mi:“MI:0914”(association)	0.590
UBA5	GAPDHS	psi-mi:“MI:0914”(association)	0.530
GSTA1	GSTA4	psi-mi:“MI:0914”(association)	0.530
RAB6B	SBF1	psi-mi:“MI:0914”(association)	0.530
RECK	IFNA4	psi-mi:“MI:0914”(association)	0.530
RAB30	UBB	psi-mi:“MI:0914”(association)	0.530
UBE2D2	UBB	psi-mi:“MI:0914”(association)	0.530
ACAA1	PEX7	psi-mi:“MI:0914”(association)	0.530
LHFPL4	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
TMEM171	B3GAT3	psi-mi:“MI:0914”(association)	0.530
CAT	NUDT19	psi-mi:“MI:0914”(association)	0.420
ACOX1	HSD17B7	psi-mi:“MI:0915”(physical association)	0.400
LRRC66	ACOX1	psi-mi:“MI:0915”(physical association)	0.400
MBNL2	ACOX1	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
	MYO9A	psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), CAT (Co-fractionation), NUP62 (Co-fractionation), PPWD1 (Co-fractionation), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS)

ESM2 similar proteins: B1WC61, B3DMA2, O32176, O64894, O65201, P07872, P12007, P15650, P26440, P28330, P45953, P45954, P48818, P49748, P50544, P51174, P70584, P79273, P79274, Q0NXR6, Q15067, Q3SZI8, Q3SZP5, Q47146, Q54IM8, Q54RR5, Q5EAD4, Q5R778, Q5RBD5, Q5RC19, Q5RF40, Q5ZHT1, Q60HI0, Q64428, Q6JQN1, Q709F0, Q80XL6, Q8HXY7, Q8JZN5, Q8X7R2

Diamond homologs: A0R502, A5A6I0, A8WP91, A8XNF0, B1WC61, B9U6P5, C3UVB0, D3JV03, F8GVD3, G3KIM8, H6LGM6, J7TF92, K4L7X3, O32176, O34421, O54143, P08503, P0A9U8, P0A9U9, P0A9V0, P11310, P12007, P15650, P15651, P16219, P26440, P28330, P41367, P45857, P45867, P45952, P45953, P45954, P46703, P48818, P49748, P50544, P51174, P52042, P63428

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ACOX1	“down-regulates quantity by destabilization”	TP73	binding
SIRT5	“down-regulates activity”	ACOX1	“catalytic activity”
TYSND1	“up-regulates activity”	ACOX1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peroxisomal protein import	13	30.0×	1e-13
Protein localization	6	15.2×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
fatty acid beta-oxidation	5	19.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	38
Uncertain significance	360
Likely benign	401
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1030736	NM_004035.7(ACOX1):c.270-1_277delinsA	Pathogenic
1252014	NM_004035.7(ACOX1):c.431-1G>A	Pathogenic
1322753	NM_004035.7(ACOX1):c.358C>T (p.Gln120Ter)	Pathogenic
1335961	NM_004035.7(ACOX1):c.551C>G (p.Ser184Ter)	Pathogenic
1396619	NM_004035.7(ACOX1):c.879_882del (p.Ser294fs)	Pathogenic
1415947	NC_000017.10:g.(?73951637)(73956466_?)del	Pathogenic
1458434	NM_004035.7(ACOX1):c.1119del (p.Thr374fs)	Pathogenic
1459059	NM_004035.7(ACOX1):c.468T>A (p.Tyr156Ter)	Pathogenic
1498	NG_008190.1:g.(?18821)(36526_?)del	Pathogenic
1499	NM_004035.7(ACOX1):c.832A>G (p.Met278Val)	Pathogenic
1500	NM_004035.7(ACOX1):c.532G>T (p.Gly178Cys)	Pathogenic
1501	NM_004035.7(ACOX1):c.926A>G (p.Gln309Arg)	Pathogenic
1502	NM_004035.7(ACOX1):c.442C>T (p.Arg148Ter)	Pathogenic
1503	NM_004035.7(ACOX1):c.372_389del (p.Phe124_Asn129del)	Pathogenic
1504	NG_008190.1:g.(22608_?)_(?_41151)del	Pathogenic
1685498	NM_004035.7(ACOX1):c.280C>T (p.Arg94Ter)	Pathogenic
1691302	NM_004035.7(ACOX1):c.904C>T (p.Arg302Ter)	Pathogenic
2013180	NM_004035.7(ACOX1):c.1599del (p.His532_Tyr533insTer)	Pathogenic
2040363	NM_004035.7(ACOX1):c.193del (p.Arg65fs)	Pathogenic
2066414	NM_004035.7(ACOX1):c.33del (p.Ala12fs)	Pathogenic
2110077	NM_004035.7(ACOX1):c.1406del (p.Ala469fs)	Pathogenic
2425011	NC_000017.10:g.(?73956286)(73956466_?)del	Pathogenic
2501787	NM_004035.7(ACOX1):c.1728+1G>A	Pathogenic
2680344	NM_004035.7(ACOX1):c.1276_1277del (p.Val426fs)	Pathogenic
2696493	NM_004035.7(ACOX1):c.909C>G (p.Tyr303Ter)	Pathogenic
2702029	NM_004035.7(ACOX1):c.684del (p.Lys229fs)	Pathogenic
2708348	NM_004035.7(ACOX1):c.979C>T (p.Gln327Ter)	Pathogenic
2715288	NM_004035.7(ACOX1):c.1100del (p.Leu367fs)	Pathogenic
2762969	NM_004035.7(ACOX1):c.211del (p.Met70_Val71insTer)	Pathogenic
2815737	NM_004035.7(ACOX1):c.525G>A (p.Trp175Ter)	Pathogenic

SpliceAI

2152 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75946793:GACCT:G	acceptor_loss	1.0000
17:75946794:ACCT:A	acceptor_loss	1.0000
17:75946795:CCTGT:C	acceptor_loss	1.0000
17:75946796:C:CG	acceptor_loss	1.0000
17:75946797:T:G	acceptor_loss	1.0000
17:75948245:TTTTA:T	donor_loss	1.0000
17:75948246:TTTA:T	donor_loss	1.0000
17:75948247:TTA:T	donor_loss	1.0000
17:75948248:TAC:T	donor_loss	1.0000
17:75948249:A:C	donor_loss	1.0000
17:75948250:CCT:C	donor_gain	1.0000
17:75948345:T:TA	donor_gain	1.0000
17:75948455:CCCCT:C	acceptor_loss	1.0000
17:75948456:CC:C	acceptor_gain	1.0000
17:75948457:CC:C	acceptor_gain	1.0000
17:75948457:CCT:C	acceptor_loss	1.0000
17:75948458:C:CC	acceptor_gain	1.0000
17:75948458:CTAA:C	acceptor_loss	1.0000
17:75948459:T:A	acceptor_loss	1.0000
17:75949212:CTGA:C	donor_loss	1.0000
17:75949213:TGA:T	donor_loss	1.0000
17:75949214:GACCT:G	donor_loss	1.0000
17:75949215:AC:A	donor_loss	1.0000
17:75949216:C:CT	donor_loss	1.0000
17:75949356:TGTGC:T	acceptor_gain	1.0000
17:75949361:C:CC	acceptor_gain	1.0000
17:75949717:CCTGG:C	donor_gain	1.0000
17:75951409:TCATA:T	donor_loss	1.0000
17:75951410:CATA:C	donor_loss	1.0000
17:75951411:ATAC:A	donor_gain	1.0000

AlphaMissense

4369 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75953550:C:A	R282M	1.000
17:75950808:C:G	G422R	0.999
17:75950808:C:T	G422R	0.999
17:75950938:C:A	K378N	0.999
17:75950938:C:G	K378N	0.999
17:75953550:C:G	R282T	0.999
17:75955621:A:G	L240P	0.999
17:75957471:A:G	W176R	0.999
17:75957471:A:T	W176R	0.999
17:75957474:A:G	W175R	0.999
17:75957474:A:T	W175R	0.999
17:75957475:T:A	K174N	0.999
17:75957475:T:G	K174N	0.999
17:75957509:A:G	F163S	0.999
17:75957537:C:G	A154P	0.999
17:75957566:C:T	G144E	0.999
17:75950807:C:A	G422V	0.998
17:75950807:C:T	G422E	0.998
17:75950810:T:A	E421V	0.998
17:75950894:C:G	R393P	0.998
17:75950940:T:C	K378E	0.998
17:75950961:G:C	H371D	0.998
17:75953483:G:C	S304R	0.998
17:75953483:G:T	S304R	0.998
17:75953485:T:G	S304R	0.998
17:75955627:C:T	G238D	0.998
17:75955629:A:C	N237K	0.998
17:75955629:A:T	N237K	0.998
17:75955857:C:G	R210P	0.998
17:75955858:G:T	R210S	0.998

dbSNP variants (sampled 300 via entrez): RS1000009813 (17:75941171 T>C,G), RS1000059064 (17:75977297 G>A,C), RS1000250199 (17:75963498 G>A,C), RS1000383161 (17:75943198 G>A,C,T), RS1000383989 (17:75947360 G>A), RS1000431896 (17:75972368 G>A,T), RS1000486808 (17:75950684 G>A,C,T), RS1000492539 (17:75976964 T>C), RS1000589477 (17:75958904 T>C), RS1000624397 (17:75941731 C>T), RS1000832469 (17:75948785 C>A), RS1000905469 (17:75946320 G>C), RS1001024185 (17:75956418 C>T), RS1001156806 (17:75953174 G>C), RS1001157657 (17:75963705 A>G)

Disease associations

OMIM: gene MIM:609751 | disease phenotypes: MIM:264470, MIM:618960, MIM:610168

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisomal acyl-CoA oxidase deficiency	Definitive	Autosomal recessive
Mitchell syndrome	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Mitchell syndrome	Definitive	AD
peroxisomal acyl-CoA oxidase deficiency	Definitive	AR

Mondo (3): peroxisomal acyl-CoA oxidase deficiency (MONDO:0009919), Mitchell syndrome (MONDO:0030073), Loeys-Dietz syndrome 2 (MONDO:0012427)

Orphanet (4): Peroxisomal acyl-CoA oxidase deficiency (Orphanet:2971), Mitchell Syndrome (Orphanet:631248), Marfan syndrome type 2 (Orphanet:284973), Marfan syndrome (Orphanet:558)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000248	Brachycephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000545	Myopia
HP:0000580	Pigmentary retinopathy
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000654	Decreased light- and dark-adapted electroretinogram amplitude
HP:0000668	Hypodontia
HP:0000737	Irritability
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001298	Encephalopathy
HP:0001319	Neonatal hypotonia
HP:0001332	Dystonia
HP:0001344	Absent speech

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003013_1	White matter hyperintensity burden	5.000000e-19
GCST003013_15	White matter hyperintensity burden	3.000000e-19
GCST004279_5	Systolic blood pressure	3.000000e-08
GCST007094_220	Diastolic blood pressure	8.000000e-07
GCST007096_255	Pulse pressure	8.000000e-09
GCST007097_92	Pulse pressure	6.000000e-06
GCST007099_114	Systolic blood pressure	2.000000e-12
GCST008158_109	Body mass index	2.000000e-06
GCST009733_92	Urinary metabolite levels in chronic kidney disease	2.000000e-28
GCST012580_4	White matter hyperintensities	2.000000e-09
GCST90002395_275	Mean platelet volume	4.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004340	body mass index
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537783	Aortic aneurysm, familial thoracic 3 (supp.)
C536662	Peroxisomal ACYL-COA oxidase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105748 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 33,333 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL276832	HYDRALAZINE	4	23,794
CHEMBL1908391	MASITINIB	3	2,808

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 7 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.85	Kd	14	nM	MASITINIB
6.57	Kd	271	nM	ALECTINIB
6.38	IC50	420	nM	HYDRALAZINE
5.57	Kd	2689	nM	CHEMBL5653589
5.57	ED50	2689	nM	CHEMBL5653589

PubChem BioAssay actives

4 with measured affinity, of 198 total; 4 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-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide	1424895: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0140	uM
Alectinib	1424895: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2710	uM
Hydralazine	1956429: Inhibition of human recombinant AOX in presence of NAD+ and NADPH	ic50	0.4200	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147786: Binding affinity to human ACOX1 incubated for 45 mins by Kinobead based pull down assay	kd	2.6888	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fenofibrate	decreases reaction, increases reaction, affects cotreatment, increases expression, decreases expression	6
perfluorooctanoic acid	increases expression	5
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	5
pirinixic acid	increases expression, decreases activity	4
Cyclosporine	decreases expression	4
Benzo(a)pyrene	affects cotreatment, decreases reaction, increases expression, decreases expression, increases methylation	3
Glucose	decreases expression, decreases reaction, increases reaction, affects cotreatment, increases expression	3
Oleic Acid	decreases expression, decreases reaction, increases expression, affects cotreatment	3
Palmitic Acid	decreases reaction, increases reaction, affects cotreatment, decreases expression	3
trichostatin A	affects cotreatment, increases expression	2
ciprofibrate	affects cotreatment, increases expression	2
tebuconazole	affects cotreatment, decreases expression	2
entinostat	affects cotreatment, increases expression	2
GW 4064	affects cotreatment, decreases expression	2
GW 7647	affects cotreatment, increases expression	2
Rosiglitazone	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Bezafibrate	increases expression	2
Fatty Acids, Nonesterified	increases reaction, affects expression, affects cotreatment, increases expression, decreases expression (+1 more)	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Triclosan	decreases expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
hugan qingzhi	increases expression, decreases expression, decreases reaction, increases reaction, affects cotreatment	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
methylmercuric chloride	increases expression	1
lasiocarpine	decreases 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
CHEMBL3991608	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9R45	GM18365	Finite cell line	Male
CVCL_C7ZE	HAP1 ACOX1 (-) 1	Cancer cell line	Male
CVCL_C7ZF	HAP1 ACOX1 (-) 2	Cancer cell line	Male
CVCL_E0TG	Ubigene Hep G2 ACOX1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)