ACOT8

acyl-CoA thioesterase 8, the group of Acyl-CoA thioesterases

Basic information

Region (hg38): 20:45841721-45857405

Previous symbols: [ "PTE1" ]

Links

ENSG00000101473 ∙ NCBI:10005 ∙ OMIM:608123 ∙ HGNC:15919 ∙ Uniprot:O14734 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACOT8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACOT8 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						0
missense			21	2		23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	21	2	0

Variants in ACOT8

This is a list of pathogenic ClinVar variants found in the ACOT8 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-45843533-A-G		not specified	Uncertain significance (May 07, 2024)
20-45843554-G-A		not specified	Uncertain significance (Apr 12, 2023)
20-45843568-G-A		not specified	Uncertain significance (Feb 23, 2023)
20-45843568-G-C		not specified	Uncertain significance (Jul 13, 2021)
20-45843571-C-T		not specified	Uncertain significance (Jul 11, 2023)
20-45843581-C-T		not specified	Uncertain significance (Oct 29, 2021)
20-45843680-T-C		not specified	Uncertain significance (Mar 07, 2024)
20-45844271-C-A		not specified	Uncertain significance (Sep 22, 2023)
20-45844335-G-T		not specified	Uncertain significance (Jul 13, 2021)
20-45844367-T-C		not specified	Uncertain significance (Jul 30, 2023)
20-45844379-C-T		not specified	Uncertain significance (Jul 14, 2021)
20-45844407-G-C		not specified	Uncertain significance (Jun 17, 2024)
20-45844416-G-A		not specified	Uncertain significance (Mar 14, 2023)
20-45848464-A-C		not specified	Uncertain significance (Sep 01, 2021)
20-45848570-A-G		not specified	Uncertain significance (Jun 13, 2023)
20-45848633-C-T		not specified	Uncertain significance (Jun 27, 2022)
20-45848639-C-T		not specified	Uncertain significance (Jul 26, 2021)
20-45848658-C-T		not specified	Uncertain significance (Oct 13, 2023)
20-45848670-G-A		not specified	Uncertain significance (Apr 05, 2023)
20-45855192-C-T		not specified	Uncertain significance (Jan 24, 2024)
20-45855198-C-T		not specified	Uncertain significance (Nov 18, 2022)
20-45855248-T-A		not specified	Uncertain significance (May 22, 2023)
20-45855270-C-T		not specified	Likely benign (Mar 01, 2023)
20-45857228-T-A		not specified	Likely benign (Aug 10, 2021)
20-45857246-G-A		not specified	Uncertain significance (Mar 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACOT8	protein_coding	protein_coding	ENST00000217455	6	15686

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000597	0.893	122203	141	3404	125748	0.0142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.124	194	199	0.975	0.0000116	2061
Missense in Polyphen		70	73.648	0.95047		729
Synonymous	0.0860	82	83.0	0.988	0.00000497	640
Loss of Function	1.56	11	18.2	0.605	0.00000113	160

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00280	0.00272
Ashkenazi Jewish	0.0257	0.0251
East Asian	0.0261	0.0231
Finnish	0.000309	0.000277
European (Non-Finnish)	0.00343	0.00298
Middle Eastern	0.0261	0.0231
South Asian	0.0892	0.0818
Other	0.0112	0.00998

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acyl-coenzyme A (acyl-CoA) thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH (PubMed:9299485, PubMed:9153233, PubMed:15194431). Competes with bile acid CoA:amino acid N-acyltransferase (BAAT) for bile acid-CoA substrate (such as chenodeoxycholoyl-CoA). Shows a preference for medium-length fatty acyl-CoAs (C2 to C20) (PubMed:9299485, PubMed:9153233). Inactive towards substrates with more than C20 aliphatic chains (PubMed:9153233). Involved in the metabolic regulation of peroxisome proliferation (PubMed:15194431). {ECO:0000269|PubMed:15194431, ECO:0000269|PubMed:9153233, ECO:0000269|PubMed:9299485}.
• Pathway: Peroxisome - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);Metabolism of lipids;alpha-linolenic acid (ALA) metabolism;Metabolism of proteins;alpha-linolenic (omega3) and linoleic (omega6) acid metabolism;Tyrosine metabolism;Leukotriene metabolism;Beta-oxidation of pristanoyl-CoA;Saturated fatty acids beta-oxidation;Beta-oxidation of very long chain fatty acids;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;palmitate biosynthesis;Bile acid biosynthesis;De novo fatty acid biosynthesis;acyl-CoA hydrolysis (Consensus)

Recessive Scores

• pRec: 0.412

Intolerance Scores

• loftool: 0.262
• rvis_EVS: 0.11
• rvis_percentile_EVS: 62

Haploinsufficiency Scores

• pHI: 0.211
• hipred: N
• hipred_score: 0.350
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acot8

Gene ontology

• Biological process: protein targeting to peroxisome;acyl-CoA metabolic process;bile acid biosynthetic process;fatty acid catabolic process;viral process;peroxisome fission;fatty acid beta-oxidation using acyl-CoA oxidase;alpha-linolenic acid metabolic process;dicarboxylic acid catabolic process;negative regulation of CD4 biosynthetic process
• Cellular component: peroxisomal matrix;cytosol
• Molecular function: acetyl-CoA hydrolase activity;signaling receptor binding;protein binding;CoA hydrolase activity;palmitoyl-CoA hydrolase activity;choloyl-CoA hydrolase activity;acyl-CoA hydrolase activity;carboxylic ester hydrolase activity;medium-chain acyl-CoA hydrolase activity;long-chain acyl-CoA hydrolase activity