ACADS Gene (Acyl-CoA Dehydrogenase Short Chain)
Genetic and Functional Insights into ACADS, a Key Enzyme in Mitochondrial Fatty Acid Beta-Oxidation
Gene Information Card
| Symbol | ACADS |
|---|---|
| Full Name | Acyl-CoA Dehydrogenase Short Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 35 ncbi.nlm.nih.gov/gene/35 |
| Ensembl ID | ENSG00000122971 |
| UniProt ID | P16219 |
| OMIM ID | 606885 |
| HGNC ID | 90 |
| Aliases | SCAD, ACAD3 |
Description
The ACADS gene encodes short-chain acyl-CoA dehydrogenase (SCAD), a mitochondrial enzyme that catalyzes the initial step of short-chain fatty acid beta-oxidation. SCAD specifically dehydrogenates butyryl-CoA and hexanoyl-CoA to their corresponding enoyl-CoA derivatives. Mutations in ACADS can lead to short-chain acyl-CoA dehydrogenase deficiency (SCADD), a metabolic disorder characterized by variable clinical phenotypes including metabolic acidosis, hypoglycemia, and developmental delay.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Short-chain acyl-CoA dehydrogenase deficiency (SCADD) | Loss-of-function mutations in ACADS impair beta-oxidation of short-chain fatty acids, leading to accumulation of butyrylcarnitine and ethylmalonic acid. | ClinVar, OMIM |
| Ethylmalonic encephalopathy | Secondary dysfunction due to ACADS deficiency may contribute to ethylmalonic acid accumulation, though primary etiology involves ETHE1 mutations. | OMIM |
| Hypoglycemia, metabolic acidosis | Insufficient energy production from fatty acids during fasting due to defective SCAD enzyme activity. | NCBI Gene, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Heart | 9.8 | Medium |
| Skeletal Muscle | 8.2 | Medium |
| Kidney | 7.1 | Medium |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocyte cell line |
| K-562 | 6.5 | Lymphoblast cell line |
| HeLa | 5.8 | Cervical carcinoma cell line |
| A549 | 4.9 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.319C>T (p.Arg107Cys) | Missense | Common | Reduced enzyme activity, associated with mild SCADD |
| c.625G>A (p.Gly209Ser) | Missense | Rare | Impaired catalytic function, severe phenotype |
| c.1058C>T (p.Thr353Met) | Missense | Rare | Decreased protein stability and activity |
| c.164C>T (p.Pro55Leu) | Missense | Rare | Loss of function, pathogenic |
Mutation functional classification
Loss of Function (LOF)
Most ACADS mutations result in partial or complete loss of enzyme activity, leading to SCAD deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ACADS.
Dominant Negative (DN)
No dominant-negative effects have been described; SCADD is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003995 - acyl-CoA dehydrogenase activity | • GO:0005739 - mitochondrion |
| • GO:0006635 - fatty acid beta-oxidation | • GO:0050660 - flavin adenine dinucleotide binding |
| • GO:0016627 - oxidoreductase activity | • acting on the CH-CH group of donors |
Pathways
• Mitochondrial fatty acid beta-oxidation (Reactome: R-HSA-77289)
• Metabolism of lipids (Reactome: R-HSA-556833)
Protein Summary
Short-chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric mitochondrial flavoprotein of approximately 44 kDa per subunit. It catalyzes the alpha,beta-dehydrogenation of short-chain acyl-CoA esters (C4-C6) using FAD as a cofactor. The enzyme is essential for energy production from fatty acids during periods of fasting or increased metabolic demand. Defects in SCAD lead to accumulation of butyrylcarnitine and ethylmalonic acid, with clinical manifestations ranging from asymptomatic to severe metabolic decompensation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACADS Knockout HEK293 Cell Line | EDJ-KQ3992 | Human | 35 | Details Get a Quote |
| ACADSB Knockout HEK293 Cell Line | EDJ-KQ3993 | Human | 36 | Details Get a Quote |
| ACADSB Knockout A-549 Cell Line | EDJ-KQ24966 | Human | 36 | Details Get a Quote |
| ACADS Knockout A-549 Cell Line | EDJ-KQ26308 | Human | 35 | Details Get a Quote |
| ACADS Knockout HCT 116 Cell Line | EDJ-KQ26309 | Human | 35 | Details Get a Quote |
| ACADS Knockout HeLa Cell Line | EDJ-KQ26310 | Human | 35 | Details Get a Quote |
| ACADSB Knockout HCT 116 Cell Line | EDJ-KQ26312 | Human | 36 | Details Get a Quote |
| ACADSB Knockout HeLa Cell Line | EDJ-KQ26313 | Human | 36 | Details Get a Quote |
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