ACSL6
protein-codingacyl-CoA synthetase long chain family member 6, the group of Acyl-CoA synthetase family
Gene summary
The protein encoded by this gene catalyzes the formation of acyl-CoA from fatty acids, ATP, and CoA, using magnesium as a cofactor. The encoded protein plays a major role in fatty acid metabolism in the brain. Translocations with the ETV6 gene are causes of myelodysplastic syndrome with basophilia, acute myelogenous leukemia with eosinophilia, and acute eosinophilic leukemia. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2011]
- FACL6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.3 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 ACSL6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001009185.3. 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 | 4 | 2 | 6 | |||
| missense | 73 | 3 | 76 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 75 | 7 | 2 | 84 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001009185.1 | 21 | MANE Select | |
| Ensembl | ENSP00000499063.2 | 21 | MANE Select | |
| RefSeq | NP_001192176.1 | 21 | Standard | |
| RefSeq | NP_001192177.1 | 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
- acyl-CoA metabolic process
- neuroblast proliferation
- long-chain fatty-acyl-CoA biosynthetic process
Molecular Function
- long-chain fatty acid-CoA ligase activity
- ATP binding
- protein homodimerization activity
- decanoate-CoA ligase activity
Cellular Component
- mitochondrial outer membrane
- peroxisomal membrane
- endoplasmic reticulum membrane
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379264
- Coding exons
- 21
- Length
- 205254
- Individuals with no LoFs
- 125705
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 43
- Defined
- 125748
- p
- 0.000171
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.76 | 321 | 423 | 0.759 | 0.0000239 | 4700 |
| Missense (PolyPhen) | 111 | 175.37 | 0.63296 | 1922 | ||
| Synonymous | -1.23 | 180 | 160 | 1.12 | 0.00000934 | 1418 |
| Loss of Function | 4.29 | 13 | 43.5 | 0.299 | 0.00000212 | 490 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Plays an important role in fatty acid metabolism in brain and the acyl-CoAs produced may be utilized exclusively for the synthesis of the brain lipid.;
- Disease
- DISEASE: Note=A chromosomal aberration involving ACSL6 may be a cause of myelodysplastic syndrome with basophilia. Translocation t(5;12)(q31;p13) with ETV6. {ECO:0000269|PubMed:10502316}.; DISEASE: Note=A chromosomal aberration involving ACSL6 may be a cause of acute myelogenous leukemia with eosinophilia. Translocation t(5;12)(q31;p13) with ETV6. {ECO:0000269|PubMed:10502316}.; DISEASE: Note=A chromosomal aberration involving ACSL6 may be a cause of acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ETV6. {ECO:0000269|PubMed:10502316}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.803
- RVIS EVS
- -0.64
- RVIS percentile EVS
- 16.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.954
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |