ACOT8

protein-coding

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

Gene summary

The protein encoded by this gene is a peroxisomal thioesterase that appears to be involved more in the oxidation of fatty acids rather than in their formation. The encoded protein can bind to the human immunodeficiency virus-1 protein Nef, and mediate Nef-induced down-regulation of CD4 in T-cells. [provided by RefSeq, Oct 2010]

Previous symbols:

PTE1

MANE transcript

NM_005469.4

Inheritance

—

ClinVar variants

U:49B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr20:45,841,721-45,857,405

External References & Databases

Ensembl (ENSG00000101473)

Transcript & Mutation Effects

hg38 • Region Span ~15.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACOT8 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 46

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005469.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			46 clinvar	3 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	49	3	0	52

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005469.4	RefSeq	NP_005460.2	6	MANE Select
ENST00000217455.9	Ensembl	ENSP00000217455.4	6	MANE Select
ENST00000426915.1	Ensembl	ENSP00000416217.1	3	Standard
ENST00000457981.5	Ensembl	ENSP00000403862.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Peroxisome - Homo sapiens (human)
Primary bile acid biosynthesis - Homo sapiens (human)
Metabolism of lipids
alpha-linolenic acid (ALA) metabolism
Metabolism of proteins

Biological Process

protein targeting to peroxisome
acyl-CoA metabolic process
bile acid biosynthetic process
fatty acid catabolic process
viral process

Molecular Function

acetyl-CoA hydrolase activity
signaling receptor binding
protein binding
CoA hydrolase activity
palmitoyl-CoA hydrolase activity

Cellular Component

peroxisomal matrix
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217455
Coding exons: 6
Length: 15686
Individuals with no LoFs: 122203
Homozygous LoFs: 141
Heterozygous LoFs: 3404
Defined: 125748
p: 0.0142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.124	194	199	0.975	0.0000116	2061
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0012	notable
Latino/Admixed American	0.0016	0.0014	notable
Ashkenazi Jewish	0.026	0.025	notable
East Asian	0.026	0.023	notable
Finnish	0.00031	0.00028	rare
European (Non-Finnish)	0.0034	0.0030	notable
South Asian	0.089	0.082	notable
Other	0.011	0.010	notable

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.412

Intolerance Scores

LoFtool: 0.262
RVIS EVS: 0.11
RVIS percentile EVS: 62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.981

Gene Damage Prediction

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