ACOX1

acyl-CoA oxidase 1

Basic information

Region (hg38): 17:75941506-75979177

Links

ENSG00000161533 ∙ NCBI:51 ∙ OMIM:609751 ∙ HGNC:119 ∙ Uniprot:Q15067 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Mitchell syndrome (Strong), mode of inheritance: AD
• peroxisomal acyl-CoA oxidase deficiency (Definitive), mode of inheritance: AR
• peroxisomal acyl-CoA oxidase deficiency (Strong), mode of inheritance: AR
• peroxisomal acyl-CoA oxidase deficiency (Supportive), mode of inheritance: AR
• Mitchell syndrome (Strong), mode of inheritance: AD
• peroxisomal acyl-CoA oxidase deficiency (Strong), mode of inheritance: AR
• Mitchell syndrome (Strong), mode of inheritance: AD
• peroxisomal acyl-CoA oxidase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitchell syndrome	AD	Allergy/Immunology/Infectious	The condition has been described as manifesting with episodic demyelination, sensorimotor polyneuropathy, and hearing loss, and early diagnosis may allow medical management (eg, immunomodulatory and related treatments have been reported to show some clinical benefits in individuals)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Craniofacial; Neurologic; Ophthalmologic	2894756; 8040306; 8279468; 11815777; 17458872; 18536048; 32169171

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACOX1 gene.

• Acyl-CoA oxidase deficiency (615 variants)
• not provided (70 variants)
• Mitchell syndrome (28 variants)
• Inborn genetic diseases (24 variants)
• not specified (8 variants)
• Acyl-CoA oxidase deficiency;Mitchell syndrome (3 variants)
• ACOX1-related condition (2 variants)
• ACOX1-related disorders (1 variants)
• Muscle weakness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACOX1 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			1	192	6	199
missense		4	135	4	2	145
nonsense	9	3				12
start loss						0
frameshift	12	12		1		25
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	11				14
splice region			7	28		35
non coding			108	69	46	223
Total	24	30	245	266	54

Highest pathogenic variant AF is 0.0000197

Variants in ACOX1

This is a list of pathogenic ClinVar variants found in the ACOX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-75941584-T-C		Acyl-CoA oxidase deficiency	Benign (Jan 13, 2018)
17-75941614-T-C		Acyl-CoA oxidase deficiency	Likely benign (Jan 13, 2018)
17-75941624-T-C		Acyl-CoA oxidase deficiency	Benign (Jan 13, 2018)
17-75941631-T-G		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75941656-T-C		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75941711-A-G		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 12, 2018)
17-75941720-A-C		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75941748-C-A		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75941872-G-A		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75941915-CAT-C		Acyl-CoA oxidase deficiency	Uncertain significance (Jun 14, 2016)
17-75941928-A-G		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 12, 2018)
17-75941942-T-C		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75941982-C-T		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75942158-C-T		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 12, 2018)
17-75942163-G-A		Acyl-CoA oxidase deficiency	Benign (Jan 13, 2018)
17-75942169-G-A		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 12, 2018)
17-75942197-G-A		Acyl-CoA oxidase deficiency	Likely benign (Jan 13, 2018)
17-75942232-C-T		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 12, 2018)
17-75942258-T-C		Acyl-CoA oxidase deficiency	Benign (Jan 12, 2018)
17-75942259-G-A		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)
17-75942264-T-C		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 12, 2018)
17-75942275-C-CA		Acyl-CoA oxidase deficiency	Likely benign (Jun 14, 2016)
17-75942304-C-T		Acyl-CoA oxidase deficiency	Benign (Jan 13, 2018)
17-75942308-G-A		Acyl-CoA oxidase deficiency	Uncertain significance (Jun 14, 2016)
17-75942361-C-G		Acyl-CoA oxidase deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACOX1	protein_coding	protein_coding	ENST00000293217	14	37928

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0621	0.938	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	258	364	0.708	0.0000209	4363
Missense in Polyphen		72	126.42	0.56954		1470
Synonymous	0.225	132	135	0.975	0.00000817	1259
Loss of Function	3.97	9	34.0	0.265	0.00000190	384

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000268	0.000268
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the desaturation of acyl-CoAs to 2-trans- enoyl-CoAs. Isoform 1 shows highest activity against medium-chain fatty acyl-CoAs and activity decreases with increasing chain length. Isoform 2 is active against a much broader range of substrates and shows activity towards very long-chain acyl-CoAs. Isoform 2 is twice as active as isoform 1 against 16-hydroxy- palmitoyl-CoA and is 25% more active against 1,16-hexadecanodioyl- CoA. {ECO:0000269|PubMed:17458872, ECO:0000269|PubMed:17603022}.
• Pathway: Peroxisome - Homo sapiens (human);Biosynthesis of unsaturated fatty acids - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);alpha-Linolenic acid metabolism - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Estrogen Receptor Pathway;Nuclear Receptors Meta-Pathway;PPAR signaling pathway;mechanism of gene regulation by peroxisome proliferators via ppara;Metabolism of lipids;alpha-linolenic acid (ALA) metabolism;Metabolism of proteins;alpha-linolenic (omega3) and linoleic (omega6) acid metabolism;Tyrosine metabolism;3-oxo-10R-octadecatrienoate beta-oxidation;Leukotriene metabolism;Omega-3 fatty acid metabolism;Saturated fatty acids beta-oxidation;Trihydroxycoprostanoyl-CoA beta-oxidation;Beta-oxidation of very long chain fatty acids;Peroxisomal lipid metabolism;Metabolism;Peroxisomal protein import;Fatty acid metabolism;Mono-unsaturated fatty acid beta-oxidation;Omega-6 fatty acid metabolism;Bile acid biosynthesis;Di-unsaturated fatty acid beta-oxidation;Phytanic acid peroxisomal oxidation;Vitamin E metabolism;fatty acid β-oxidation (peroxisome);TYSND1 cleaves peroxisomal proteins (Consensus)

Recessive Scores

• pRec: 0.772

Intolerance Scores

• loftool: 0.188
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.57

Haploinsufficiency Scores

• pHI: 0.160
• hipred: Y
• hipred_score: 0.756
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acox1
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; reproductive system phenotype; immune system phenotype; liver/biliary system phenotype; neoplasm

Gene ontology

• Biological process: very long-chain fatty acid metabolic process;generation of precursor metabolites and energy;protein targeting to peroxisome;lipid metabolic process;prostaglandin metabolic process;spermatogenesis;regulation of lipid metabolic process;fatty acid oxidation;fatty acid beta-oxidation using acyl-CoA oxidase;alpha-linolenic acid metabolic process;lipid homeostasis
• Cellular component: nucleus;nucleoplasm;nucleolus;peroxisome;peroxisomal membrane;peroxisomal matrix;cytosol;plasma membrane;membrane;intracellular membrane-bounded organelle
• Molecular function: acyl-CoA oxidase activity;signaling receptor binding;fatty acid binding;palmitoyl-CoA oxidase activity;PDZ domain binding;protein N-terminus binding;flavin adenine dinucleotide binding;FAD binding