SLC27A2
protein-codingsolute carrier family 27 member 2, the group of Acyl-CoA synthetase family|Solute carrier family 27
Gene summary
The protein encoded by this gene is an isozyme of 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 activates long-chain, branched-chain and very-long-chain fatty acids containing 22 or more carbons to their CoA derivatives. It is expressed primarily in liver and kidney, and is present in both endoplasmic reticulum and peroxisomes, but not in mitochondria. Its decreased peroxisomal enzyme activity is in part responsible for the biochemical pathology in X-linked adrenoleukodystrophy. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]
- FACVL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~54.2 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 SLC27A2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003645.4. 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 | 2 | ||||
| missense | 98 | 5 | 103 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 1 | 0 | 101 | 7 | 0 | 109 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003636.2 | 10 | MANE Select | |
| Ensembl | ENSP00000267842.5 | 10 | MANE Select | |
| RefSeq | NP_001153101.1 | 9 | Standard | |
| Ensembl | ENSP00000370289.4 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Insulin resistance - Homo sapiens (human)
- Peroxisome - Homo sapiens (human)
- PPAR signaling pathway - Homo sapiens (human)
- Metformin Pathway, Pharmacokinetics
- Refsum Disease
Biological Process
- fatty acid alpha-oxidation
- long-chain fatty acid metabolic process
- protein targeting to peroxisome
- fatty acid beta-oxidation
- bile acid biosynthetic process
Molecular Function
- long-chain fatty acid-CoA ligase activity
- signaling receptor binding
- long-chain fatty acid transporter activity
- ATP binding
- fatty acid transmembrane transporter activity
Cellular Component
- peroxisomal membrane
- integral component of peroxisomal membrane
- endoplasmic reticulum
- endoplasmic reticulum lumen
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000267842
- Coding exons
- 10
- Length
- 54200
- Individuals with no LoFs
- 125652
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 96
- Defined
- 125748
- p
- 0.000382
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.191 | 359 | 349 | 1.03 | 0.0000174 | 4015 |
| Missense (PolyPhen) | 118 | 123.41 | 0.95613 | 1426 | ||
| Synonymous | 0.206 | 132 | 135 | 0.977 | 0.00000661 | 1236 |
| Loss of Function | 1.70 | 17 | 26.4 | 0.644 | 0.00000121 | 335 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.00049 | 0.00049 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00082 | 0.00082 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00027 | 0.00027 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acyl-CoA synthetase probably involved in bile acid metabolism. Proposed to activate C27 precursors of bile acids to their CoA thioesters derivatives before side chain cleavage via peroxisomal beta-oxidation occurs. In vitro, activates 3-alpha,7- alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol. Does not utilize C24 bile acids as substrates. In vitro, also activates long- and branched-chain fatty acids and may have additional roles in fatty acid metabolism. May be involved in translocation of long-chain fatty acids (LFCA) across membranes (By similarity). {ECO:0000250, ECO:0000269|PubMed:11980911}.;
Recessive Scores
- pRec
- 0.181
Intolerance Scores
- LoFtool
- 0.877
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.65
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.934
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |