ACSL3
protein-codingacyl-CoA synthetase long chain family member 3, the group of Acyl-CoA synthetase family
Gene summary
The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme is highly expressed in brain, and preferentially utilizes myristate, arachidonate, and eicosapentaenoate as substrates. The amino acid sequence of this isozyme is 92% identical to that of rat homolog. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
- FACL3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~83.7 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 ACSL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004457.5. 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 | 2 | 4 | ||
| missense | 67 | 4 | 71 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 73 | 5 | 2 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004448.2 | 14 | MANE Select | |
| Ensembl | ENSP00000350012.3 | 14 | MANE Select | |
| RefSeq | NP_001341087.1 | 14 | Standard | |
| RefSeq | NP_001341088.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adipocytokine signaling pathway - Homo sapiens (human)
- Peroxisome - Homo sapiens (human)
- Thermogenesis - Homo sapiens (human)
- Fatty acid degradation - Homo sapiens (human)
- Fatty acid biosynthesis - Homo sapiens (human)
Biological Process
- long-chain fatty acid metabolic process
- fatty acid biosynthetic process
- brain development
- response to nutrient
- response to organic cyclic compound
Molecular Function
- long-chain fatty acid-CoA ligase activity
- ATP binding
- protein kinase binding
- protein domain specific binding
- decanoate-CoA ligase activity
Cellular Component
- mitochondrial outer membrane
- peroxisomal membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000357430
- Coding exons
- 14
- Length
- 83706
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.01 | 283 | 396 | 0.715 | 0.0000211 | 4711 |
| Missense (PolyPhen) | 97 | 176.49 | 0.5496 | 2050 | ||
| Synonymous | -0.960 | 154 | 140 | 1.10 | 0.00000755 | 1377 |
| Loss of Function | 3.72 | 13 | 37.6 | 0.346 | 0.00000204 | 468 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000059 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. ACSL3 mediates hepatic lipogenesis (By similarity). Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates (By similarity). Has mainly an anabolic role in energy metabolism. Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins). {ECO:0000250, ECO:0000269|PubMed:18003621}.;
Recessive Scores
- pRec
- 0.186
Intolerance Scores
- LoFtool
- 0.500
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |