ETFA

Chr 15AR

electron transfer flavoprotein subunit alpha

Also known as: EMA, GA2, MADD

NCBI Gene: 2108 ENSG00000140374 UniProt: P13804 OMIM: 608053

The ETFA protein forms part of the electron transfer flavoprotein complex that accepts electrons from multiple mitochondrial dehydrogenases and transfers them to the respiratory chain, playing an essential role in fatty acid oxidation and amino acid metabolism. Biallelic mutations cause glutaric acidemia type IIA, an autosomal recessive disorder affecting mitochondrial energy metabolism. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.68), and affected individuals typically present with metabolic acidosis and distinctive organic acid profiles.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

ETFA participates in catalyzing the initial step of the mitochondrial fatty acid beta-oxidation. It shuttles electrons between primary flavoprotein dehydrogenases and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. Defects in electron-transfer-flavoprotein have been implicated in type II glutaricaciduria in which multiple acyl-CoA dehydrogenase deficiencies result in large excretion of glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glutaric acidemia IIAMIM #231680

UniProtGlutaric aciduria 2A

Clinical highlights

Gene-disease validity (ClinGen)

multiple acyl-CoA dehydrogenase deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.68

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ETFA