ACOT4
protein-codingacyl-CoA thioesterase 4, the group of Acyl-CoA thioesterases
Gene summary
Enables fatty acyl-CoA hydrolase activity and succinyl-CoA hydrolase activity. Involved in oxoacid metabolic process and succinyl-CoA metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.9 kbGenCC 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 ACOT4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152331.4. 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 | 1 | 1 | ||||
| missense | 75 | 2 | 77 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 76 | 2 | 0 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689544.3 | 3 | MANE Select | |
| Ensembl | ENSP00000323071.4 | 3 | MANE Select | |
| Ensembl | ENSP00000775294.1 | 2 | Standard | |
| Ensembl | ENSP00000658226.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Biosynthesis of unsaturated fatty acids - Homo sapiens (human)
- Fatty acid elongation - Homo sapiens (human)
- stearate biosynthesis
- Metabolism of lipids
- Metabolism of proteins
Biological Process
- very long-chain fatty acid metabolic process
- long-chain fatty acid metabolic process
- succinyl-CoA metabolic process
- protein targeting to peroxisome
- fatty acid metabolic process
Molecular Function
- succinyl-CoA hydrolase activity
- signaling receptor binding
- palmitoyl-CoA hydrolase activity
- acyl-CoA hydrolase activity
- carboxylic ester hydrolase activity
Cellular Component
- peroxisome
- peroxisomal matrix
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326303
- Coding exons
- 3
- Length
- 4791
- Individuals with no LoFs
- 115062
- Homozygous LoFs
- 2093
- Heterozygous LoFs
- 8593
- Defined
- 125748
- p
- 0.0434
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.113 | 211 | 216 | 0.978 | 0.0000102 | 2662 |
| Missense (PolyPhen) | 85 | 84.667 | 1.0039 | 1095 | ||
| Synonymous | 0.258 | 90 | 93.2 | 0.966 | 0.00000463 | 889 |
| Loss of Function | -0.127 | 12 | 11.5 | 1.04 | 5.55e-7 | 149 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.024 | 0.013 | notable |
| Latino/Admixed American | 0.032 | 0.017 | notable |
| Ashkenazi Jewish | 0.076 | 0.044 | notable |
| East Asian | 0.00054 | 0.00054 | rare |
| Finnish | 0.27 | 0.11 | notable |
| European (Non-Finnish) | 0.15 | 0.058 | notable |
| South Asian | 0.036 | 0.020 | notable |
| Other | 0.088 | 0.040 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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 (By similarity). Succinyl-CoA thioesterase that also hydrolyzes long chain saturated and unsaturated monocarboxylic acyl-CoAs. {ECO:0000250, ECO:0000269|PubMed:16940157}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.855
- RVIS EVS
- 0.28
- RVIS percentile EVS
- 71.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.172
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |