ETFRF1
Chr 12electron transfer flavoprotein regulatory factor 1
Also known as: LYRM5
The protein regulates the electron transfer flavoprotein by promoting flavin removal from the ETF holoenzyme and participates in the mitochondrial respiratory electron transport chain. Mutations cause multiple acyl-CoA dehydrogenase deficiency, an autosomal recessive disorder affecting fatty acid oxidation that can present from the neonatal period through adulthood with episodes of hypoglycemia, metabolic acidosis, and muscle weakness. The gene shows very high constraint against loss-of-function variants, indicating mutations are likely to have significant clinical consequences.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
45 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 35 |
Likely Pathogenic | — | — | — | — | 2 |
VUS | — | — | — | — | 5 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 0 |
| Total | — | 43 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ETFRF1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →No open access results found
External Resources
Links to major genomics databases and tools