ACOX2

acyl-CoA oxidase 2

Basic information

Region (hg38): 3:58505135-58537283

Links

ENSG00000168306 ∙ NCBI:8309 ∙ OMIM:601641 ∙ HGNC:120 ∙ Uniprot:Q99424 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital bile acid synthesis defect 6 (Limited), mode of inheritance: AR
• congenital bile acid synthesis defect 6 (Limited), mode of inheritance: AR
• congenital bile acid synthesis defect 6 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bile acid synthesis defect, congenital, 6	AR	Gastrointestinal	Individuals have been described with hepatic dysfunction, and avoidance of hepatotoxic agents and medical management (eg, with cholestyramine) has been described as beneficial	Gastrointestinal	27647924; 27884763

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACOX2 gene.

• not provided (109 variants)
• Inborn genetic diseases (32 variants)
• Congenital bile acid synthesis defect 6 (10 variants)
• ACOX2-related condition (5 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACOX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				24	6	30
missense			66	9	2	77
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1		1			2
splice region			4	6		10
non coding				10	7	17
Total	1	0	71	43	15

Variants in ACOX2

This is a list of pathogenic ClinVar variants found in the ACOX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-58505214-G-A		ACOX2-related disorder	Likely benign (Mar 14, 2023)
3-58505271-C-T		not specified	Uncertain significance (Mar 01, 2023)
3-58505275-G-A		ACOX2-related disorder	Likely benign (May 25, 2022)
3-58505276-G-T		not specified	Uncertain significance (Jun 09, 2022)
3-58505278-A-C			Likely benign (Mar 31, 2018)
3-58505281-G-A			Likely benign (Sep 02, 2022)
3-58505283-TCTC-T			Uncertain significance (Sep 13, 2022)
3-58505295-A-G			Likely benign (Aug 10, 2022)
3-58505304-C-T			Likely benign (Jul 17, 2023)
3-58508886-C-G			Likely benign (Sep 12, 2023)
3-58508944-G-A		ACOX2-related disorder	Likely benign (Oct 20, 2023)
3-58508949-C-T		not specified	Uncertain significance (Sep 28, 2022)
3-58508953-A-G		ACOX2-related disorder	Likely benign (Jan 02, 2024)
3-58508974-T-G		not specified	Uncertain significance (Jun 18, 2021)
3-58508981-T-C		not specified	Uncertain significance (Jul 30, 2023)
3-58509024-T-C		not specified	Uncertain significance (Feb 05, 2024)
3-58509029-G-A			Likely benign (May 28, 2022)
3-58509039-CAA-C			Likely benign (Mar 07, 2023)
3-58517191-GTC-G			Likely benign (Jan 02, 2024)
3-58517206-C-T			Uncertain significance (Jan 26, 2023)
3-58517216-G-A			Benign (Nov 07, 2023)
3-58517235-T-C			Likely benign (Nov 24, 2022)
3-58517249-C-T		not specified	Uncertain significance (May 02, 2023)
3-58517272-G-C		not specified	Conflicting classifications of pathogenicity (Dec 19, 2023)
3-58517274-G-A		ACOX2-related disorder	Likely benign (Apr 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACOX2	protein_coding	protein_coding	ENST00000302819	14	32184

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.18e-10	0.965	125082	0	666	125748	0.00265

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.502	387	416	0.931	0.0000253	4427
Missense in Polyphen		118	134	0.88062		1429
Synonymous	0.521	159	168	0.949	0.0000105	1362
Loss of Function	2.16	21	34.8	0.604	0.00000157	393

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00208	0.00208
Ashkenazi Jewish	0.00	0.00
East Asian	0.000545	0.000544
Finnish	0.00883	0.00886
European (Non-Finnish)	0.00276	0.00276
Middle Eastern	0.000545	0.000544
South Asian	0.00291	0.00291
Other	0.00245	0.00245

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Oxidizes the CoA esters of the bile acid intermediates di- and tri-hydroxycholestanoic acids. {ECO:0000269|PubMed:27884763}.
• Pathway: Peroxisome - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Quercetin and Nf-kB- AP-1 Induced Cell Apoptosis;PPAR signaling pathway;Metabolism of lipids;Metabolism of proteins;Tyrosine metabolism;Leukotriene metabolism;Beta-oxidation of pristanoyl-CoA;Omega-3 fatty acid metabolism;Saturated fatty acids beta-oxidation;Trihydroxycoprostanoyl-CoA beta-oxidation;Peroxisomal lipid metabolism;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Peroxisomal protein import;Fatty acid metabolism;Metabolism of steroids;Omega-6 fatty acid metabolism;Bile acid biosynthesis;Putative anti-Inflammatory metabolites formation from EPA;Phytanic acid peroxisomal oxidation;fatty acid β-oxidation (peroxisome);bile acid biosynthesis, neutral pathway (Consensus)

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.712
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.96

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.190
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.175

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Acox2
• Phenotype: normal phenotype

Gene ontology

• Biological process: protein targeting to peroxisome;bile acid biosynthetic process;positive regulation of cell death;fatty acid beta-oxidation using acyl-CoA oxidase;lipid homeostasis;positive regulation of response to oxidative stress
• Cellular component: peroxisome;peroxisomal matrix;cytosol;intracellular membrane-bounded organelle
• Molecular function: acyl-CoA oxidase activity;signaling receptor binding;fatty acid binding;pristanoyl-CoA oxidase activity;3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity;protein homodimerization activity;flavin adenine dinucleotide binding;FAD binding