ACSL1
protein-codingacyl-CoA synthetase long chain family member 1, 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
- FACL2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~71.2 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 ACSL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001995.5. 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 | 2 | 2 | 3 | 7 | ||
| missense | 70 | 9 | 79 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 81 | 11 | 3 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001986.2 | 20 | MANE Select | |
| Ensembl | ENSP00000281455.2 | 20 | MANE Select | |
| RefSeq | NP_001273637.1 | 20 | Standard | |
| RefSeq | NP_001273639.1 | 20 | 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
- response to nutrient
- lipid biosynthetic process
- response to organic cyclic compound
- regulation of lipid metabolic process
Molecular Function
- long-chain fatty acid-CoA ligase activity
- ATP binding
- decanoate-CoA ligase activity
Cellular Component
- mitochondrion
- mitochondrial outer membrane
- peroxisomal membrane
- endoplasmic reticulum membrane
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000515030
- Coding exons
- 20
- Length
- 71224
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125747
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 330 | 410 | 0.805 | 0.0000234 | 4552 |
| Missense (PolyPhen) | 54 | 103.31 | 0.5227 | 1221 | ||
| Synonymous | 0.439 | 153 | 160 | 0.956 | 0.0000103 | 1350 |
| Loss of Function | 4.37 | 14 | 46.0 | 0.305 | 0.00000263 | 492 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00016 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.00039 | 0.00037 | rare |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses palmitoleate, oleate and linoleate.;
Recessive Scores
- pRec
- 0.329
Intolerance Scores
- LoFtool
- 0.636
- RVIS EVS
- -0.84
- RVIS percentile EVS
- 11.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.579
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |