ETFA: Electron Transfer Flavoprotein Subunit Alpha
Essential mitochondrial protein in fatty acid oxidation and amino acid metabolism
Gene Information Card
| Symbol | ETFA |
|---|---|
| Full Name | Electron Transfer Flavoprotein Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 15q24.2-q24.3 |
| NCBI Gene ID | 2108 ncbi.nlm.nih.gov/gene/2108 |
| Ensembl ID | ENSG00000140374 |
| UniProt ID | P13804 |
| OMIM ID | 608053 |
| HGNC ID | 3481 |
| Aliases | EMA, GA2, MADD |
Description
The ETFA gene encodes the alpha subunit of the electron transfer flavoprotein (ETF), a heterodimeric mitochondrial protein that accepts electrons from several mitochondrial dehydrogenases, including those involved in fatty acid beta-oxidation, amino acid catabolism, and choline metabolism. ETF then transfers electrons to the main respiratory chain via ETF-ubiquinone oxidoreductase (ETFDH). Mutations in ETFA cause multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glutaric acidemia type II (Multiple acyl-CoA dehydrogenase deficiency) | Loss-of-function mutations in ETFA impair electron transfer from flavoprotein dehydrogenases, leading to accumulation of fatty acids and amino acid metabolites. | ClinVar, OMIM |
| Riboflavin-responsive MADD | Some ETFA mutations respond to riboflavin supplementation, improving residual ETF function. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | High |
| Heart | 15.2 | High |
| Skeletal muscle | 12.8 | High |
| Kidney | 10.1 | Medium |
| Brain | 6.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 22.1 | High expression in liver-derived line |
| K-562 | 14.5 | Moderate expression |
| HeLa | 11.3 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.797C>T (p.Thr266Met) | Missense | Common in MADD patients | Reduced ETF stability and electron transfer activity |
| c.34G>A (p.Gly12Arg) | Missense | Rare | Impaired dimerization with ETFB |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Most ETFA mutations are loss-of-function, reducing or abolishing electron transfer activity, leading to MADD.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; MADD is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • electron transfer activity (GO:0009055) | • mitochondrial matrix (GO:0005759) |
| • fatty acid beta-oxidation using acyl-CoA dehydrogenase (GO:0033539) | • acyl-CoA dehydrogenase activity (GO:0003995) |
Pathways
• Fatty acid beta-oxidation (mitochondrial)
• Valine
• leucine
• and isoleucine degradation
• Lysine degradation
• Tryptophan degradation
• Electron transport chain (ETF to ubiquinone)
Protein Summary
ETFA encodes the alpha subunit of the electron transfer flavoprotein (ETF), a 32 kDa protein that forms a heterodimer with ETFB. ETF is located in the mitochondrial matrix and serves as a specific electron acceptor for at least 10 flavoprotein dehydrogenases. The alpha subunit contains the FAD-binding domain and is essential for electron transfer to ETFDH. Defects in ETFA disrupt multiple catabolic pathways, causing MADD.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ETFA Knockout HEK293 Cell Line | EDJ-KQ4558 | Human | 2108 | Details Get a Quote |
| ETFA Knockout A-549 Cell Line | EDJ-KQ27199 | Human | 2108 | Details Get a Quote |
| ETFA Knockout HCT 116 Cell Line | EDJ-KQ27200 | Human | 2108 | Details Get a Quote |
| ETFA Knockout HeLa Cell Line | EDJ-KQ27201 | Human | 2108 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
