ETFB

Chr 19AR

electron transfer flavoprotein subunit beta

Also known as: FP585, MADD

NCBI Gene: 2109ENSG00000105379UniProt: P38117

This gene encodes electron-transfer-flavoprotein, beta polypeptide, which shuttles electrons between primary flavoprotein dehydrogenases involved in mitochondrial fatty acid and amino acid catabolism and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. The gene deficiencies have been implicated in type II glutaricaciduria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Glutaric acidemia IIBMIM #231680
AR
UniProtGlutaric aciduria 2B
412
ClinVar variants
57
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— ETFB
🧬
Gene-Disease Validity (ClinGen)
multiple acyl-CoA dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
57 Pathogenic / Likely Pathogenic· 108 VUS of 412 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.82LOEUF
pLI 0.017
Z-score 2.01
OE 0.39 (0.20–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.42Z-score
OE missense 0.92 (0.81–1.03)
183 obs / 199.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.20–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 5 / 12.7Missense obs/exp: 183 / 199.8Syn Z: 0.11

ClinVar Variant Classifications

412 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic32
VUS108
Likely Benign188
Benign43
Conflicting16
25
Pathogenic
32
Likely Pathogenic
108
VUS
188
Likely Benign
43
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
19
0
25
Likely Pathogenic
17
7
8
0
32
VUS
4
89
15
0
108
Likely Benign
0
8
73
107
188
Benign
1
2
37
3
43
Conflicting
—16
Total28106152110412

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ETFB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ETFB-related glutaric aciduria

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glutaric acidemia IIB

MIM #231680

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ETFB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deep Intronic ETFDH Variants Represent a Recurrent Pathogenic Event in Multiple Acyl-CoA Dehydrogenase Deficiency.
Martino S et al.·Int J Mol Sci
2024Case report
Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients.
Ruiz-Pinto S et al.·Breast Cancer Res Treat
2018Cohort
Riboflavin in Neurological Diseases: A Narrative Review.
Plantone D et al.·Clin Drug Investig
2021Review
Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10).
Horvath R·J Inherit Metab Dis
2012Review
Towards a kingdom of reproductive life - the core sperm proteome.
Pini T et al.·Reproduction
2025
Lysine 2-hydroxyisobutyrylation of HXK1 alters energy metabolism and K(ATP) channel function in the atrium from patients with atrial fibrillation.
Hou HT et al.·Cell Commun Signal
2025Cohort
Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients.
Ali A et al.·Genes (Basel)
2021Cohort
Literature-Guided 6-Gene Signature for the Stratification of High-Risk Acute Myeloid Leukemia.
Song JK et al.·Cancer Res Treat
2025
Disorders of flavin adenine dinucleotide metabolism: MADD and related deficiencies.
Mereis M et al.·Int J Biochem Cell Biol
2021Review
Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency.
Henriques BJ et al.·Curr Mol Med
2019Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools