ETFB

Chr 19AR

electron transfer flavoprotein subunit beta

Also known as: FP585, MADD

NCBI Gene: 2109 ENSG00000105379 UniProt: P38117 OMIM: 130410

The electron transfer flavoprotein beta subunit accepts electrons from multiple mitochondrial dehydrogenases involved in fatty acid oxidation and amino acid metabolism, then transfers them to the main respiratory chain. Mutations cause glutaric acidemia type IIB, an autosomal recessive disorder affecting mitochondrial energy metabolism. The gene shows low constraint to loss-of-function variation (pLI 0.017), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.821 OMIM phenotype

Clinical Summary— ETFB

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Gene-Disease Validity (ClinGen)

multiple acyl-CoA dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

43 unique Pathogenic / Likely Pathogenic· 106 VUS of 403 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ETFB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.017

Z-score 2.01

OE 0.39 (0.20–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.42Z-score

OE missense 0.92 (0.81–1.03)

183 obs / 199.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.20–0.82)

0≤0.351.4

Missense OE?0.92 (0.81–1.03)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 5 / 12.7Missense obs/exp: 183 / 199.8Syn Z: 0.11

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveETFB-related glutaric aciduriaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6842th %ile

GOF

0.5268th %ile

LOF

0.3550th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

403 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12

Likely Pathogenic31

VUS106

Likely Benign187

Benign43

Conflicting16

Pathogenic

Likely Pathogenic

106

VUS

187

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	0	4	0	12
Likely Pathogenic	24	7	0	0	31
VUS	4	93	9	0	106
Likely Benign	0	9	71	107	187
Benign	1	3	36	3	43
Conflicting	—				16
Total	37	112	120	110	395

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ETFB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →