ACOX2 (acyl-CoA oxidase 2)

Gene

• Entrez ID: 8309
• Gene name: Acyl-CoA oxidase 2
• Gene symbol: ACOX2
• Synonyms (NCBI Gene): BCOX, BRCACOX, BRCOX, CBAS6, THCCox
• Chromosome: 3
• Chromosome location: 3p14.3
• Summary: The product of this gene belongs to the acyl-CoA oxidase family. It encodes the branched-chain acyl-CoA oxidase which is involved in the degradation of long branched fatty acids and bile acid intermediates in peroxisomes. Deficiency of this enzyme results

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs150832314	G>A	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT028915	hsa-miR-26b-5p	Microarray	19088304
MIRT763140	hsa-miR-200b	CLIP-seq
MIRT763141	hsa-miR-200c	CLIP-seq
MIRT763142	hsa-miR-429	CLIP-seq
MIRT763143	hsa-miR-452	CLIP-seq
MIRT763144	hsa-miR-4635	CLIP-seq
MIRT763145	hsa-miR-4676-3p	CLIP-seq
MIRT763146	hsa-miR-526b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000038	Process	Very long-chain fatty acid metabolic process	IBA
GO:0003997	Function	Acyl-CoA oxidase activity	IEA
GO:0005504	Function	Fatty acid binding	IBA
GO:0005515	Function	Protein binding	IPI	28514442, 32296183, 33961781
GO:0005777	Component	Peroxisome	IBA
GO:0005777	Component	Peroxisome	IDA	2079609, 8943006
GO:0005777	Component	Peroxisome	IEA
GO:0005777	Component	Peroxisome	IMP	27884763
GO:0005777	Component	Peroxisome	ISS
GO:0005782	Component	Peroxisomal matrix	IEA
GO:0005782	Component	Peroxisomal matrix	TAS
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006631	Process	Fatty acid metabolic process	IEA
GO:0006635	Process	Fatty acid beta-oxidation	IEA
GO:0006699	Process	Bile acid biosynthetic process	IDA	27884763
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016627	Function	Oxidoreductase activity, acting on the CH-CH group of donors	IEA
GO:0033540	Process	Fatty acid beta-oxidation using acyl-CoA oxidase	IBA
GO:0033540	Process	Fatty acid beta-oxidation using acyl-CoA oxidase	IDA	27884763
GO:0033540	Process	Fatty acid beta-oxidation using acyl-CoA oxidase	IEA
GO:0033540	Process	Fatty acid beta-oxidation using acyl-CoA oxidase	IMP	27884763
GO:0033791	Function	3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity	IBA
GO:0033791	Function	3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity	IDA	27884763
GO:0033791	Function	3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity	IEA
GO:0033791	Function	3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity	ISS
GO:0042803	Function	Protein homodimerization activity	ISS
GO:0050660	Function	Flavin adenine dinucleotide binding	IBA
GO:0050660	Function	Flavin adenine dinucleotide binding	IEA
GO:0050660	Function	Flavin adenine dinucleotide binding	ISS
GO:0071949	Function	FAD binding	IEA
GO:0120524	Function	Long-chain fatty acyl-CoA oxidase activity	IBA

Other IDs

• MIM: 601641
• HGNC: 120
• e!Ensembl: ENSG00000168306

Protein

• UniProt ID: Q99424
• Protein name: Peroxisomal acyl-coenzyme A oxidase 2 (EC 1.17.99.3) (3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA 24-hydroxylase) (3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA oxidase) (Trihydroxycoprostanoyl-CoA oxidase) (THCA-CoA oxidase)
• Protein function: Oxidizes the CoA esters of the bile acid intermediates di- and tri-hydroxycholestanoic acids (PubMed:27884763). Capable of oxidizing short as well as long chain 2-methyl branched fatty acids (By similarity). {ECO:0000250|UniProtKB:P07872, ECO:00
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF14749	Acyl-CoA_ox_N	32 → 148	Acyl-coenzyme A oxidase N-terminal	Domain
  PF02770	Acyl-CoA_dh_M	150 → 260	Acyl-CoA dehydrogenase, middle domain	Domain
  PF01756	ACOX	495 → 675	Acyl-CoA oxidase	Family

• Tissue specificity: TISSUE SPECIFICITY: Present in all tissues tested: heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Most abundant in heart, liver and kidney. {ECO:0000269|PubMed:8943006}.
• Sequence:

  MGSPVHRVSLGDTWSRQMHPDIESERYMQSFDVERLTNILDGGAQNTALRRKVESIIHSY
  PEFSCKDNYFMTQNERYKAAMRRAFHIRLIARRLGWLEDGRELGYAYRALSGDVALNIHR
  VFVRALRSLGSEEQIAKWDPLCKNIQIIATYAQTELGHGTYLQGLETEATYDAATQEFVI
  HSPTLTATKWWPGDLGRSATHALVQAQLICSGARRGMHAFIVPIRSLQDHTPLPGIIIGD
  IGPKMDFDQTDNGFLQLNHVRVPRENMLSRFAQVLPDGTYVKLGTAQSNYLPMVVVRVEL
  LSGEILPILQKACVIAMRYSVIRRQSRLRPSDPEAKVLDYQTQQQKLFPQLAISYAFHFL
  AVSLLEFFQHSYTAILNQDFSFLPELHALSTGMKAMMSEFCTQGAEMCRRACGGHGYSKL
  SGLPSLVTKLSASCTYEGENTVLYLQVARFLVKSYLQTQMSPGSTPQRSLSPSVAYLTAP
  DLARCPAQRAADFLCPELYTTAWAHVAVRLIKDSVQHLQTLTQSGADQHEAWNQTTVIHL
  QAAKVHCYYVTVKGFTEALEKLENEPAIQQVLKRLCDLHAIHGILTNSGDFLHDAFLSGA
  QVDMARTAYLDLLRLIRKDAILLTDAFDFTDQCLNSALGCYDGNVYERLFQWAQKSPTNT
  QENPAYEEYIRPLLQSWRSKL

• Sequence length: 681

Pathways

KEGG:

Primary bile acid biosynthesis
Metabolic pathways
PPAR signaling pathway
Peroxisome

Reactome:

Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
Beta-oxidation of pristanoyl-CoA
Peroxisomal protein import

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Congenital bile acid synthesis defect 6	Pathogenic	rs1057519329	RCV000416307	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ACOX2-related disorder	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILE ACID SYNTHESIS DEFECT, CONGENITAL, 6	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Ataxia	Ataxia	Pubtator	27647924	Associate	★☆☆☆☆ Found in Text Mining only
BILE ACID SYNTHESIS DEFECT, CONGENITAL, 6	Congenital Bile Acid Synthesis Defect	UNIPROT_DG	27647924, 27884763		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILE ACID SYNTHESIS DEFECT, CONGENITAL, 6	Congenital Bile Acid Synthesis Defect	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILE ACID SYNTHESIS DEFECT, CONGENITAL, 6	Congenital Bile Acid Synthesis Defect	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	26183823, 29228969		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	26109344, 26183823, 29228969	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	20096344	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	39738606	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	21343950		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	27647924	Associate	★☆☆☆☆ Found in Text Mining only
Glaucoma Open Angle	Open angle glaucoma	Pubtator	36002796	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hepatoblastoma	Hepatoblastoma	BEFREE	27884763		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	20096344		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver cirrhosis	Pubtator	27647924	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	26183823, 29228969		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	26183823		★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	37632832	Associate	★☆☆☆☆ Found in Text Mining only
Vertical supranuclear gaze palsy	Supranuclear gaze palsy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Zellweger Syndrome	Zellweger Syndrome	BEFREE	8943006		★☆☆☆☆ Found in Text Mining only