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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ETFB
electron transfer flavoprotein subunit beta
Chromosome 19 · 19q13.41
NCBI Gene: 2109Ensembl: ENSG00000105379.11HGNC: HGNC:3482UniProt: P38117
117PubMed Papers
21Diseases
0Drugs
39Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingelectron transfer activityamino acid catabolic processrespiratory electron transport chainmultiple acyl-CoA dehydrogenase deficiencyElevated circulating glutaric acid concentrationglutaric aciduriamultiple acyl-CoA dehydrogenase deficiency, mild type
✦AI Summary

ETFB (electron transfer flavoprotein subunit beta) is a critical mitochondrial matrix protein that functions as the β-subunit of the heterodimeric electron transfer flavoprotein complex. ETFB accepts electrons from multiple mitochondrial dehydrogenases, including acyl-CoA dehydrogenases and sarcosine dehydrogenase, transferring them to the main respiratory chain via ETF-ubiquinone oxidoreductase 1. This electron shuttle activity is essential for normal mitochondrial fatty acid oxidation and amino acid catabolism. ETFB contains a structurally important bound AMP molecule 1. Deficiency of ETFB causes glutaric acidemia type II (glutaric aciduria 2B), an inherited metabolic disorder characterized by severe hypoketotic hypoglycemia, acidosis, and potential neonatal fatality 1. ETFB emerges as a relevant biomarker in diverse pathological contexts: elevated ETFB levels correlate with worse renal dysfunction in congenital hydronephrosis 2, serve as a diagnostic marker for leptospiral infection 3, and predict poor overall survival in acute myeloid leukemia patients 4. Proteomically, decreased ETFB in cerebrospinal fluid and cortex associates with mitochondrial dysfunction in Alzheimer's disease, highlighting broader neurological relevance 5. Additionally, ETFB-related metabolic disorders respond to riboflavin supplementation, reflecting the protein's flavin-dependent function 6.

Sources cited
1
ETFB heterodimerizes with ETFA as electron acceptor for dehydrogenases and transfers electrons via ETFDH to respiratory chain; ETFB deficiency causes glutaric acidemia type II with hypoketotic hypoglycemia and acidosis
PMID: 8617498
2
ETFB protein expression is upregulated in hydronephrotic kidneys and correlates negatively with split renal function, suggesting utility as a biomarker for renal injury
PMID: 27840937
3
ETFB protein from Leptospira interrogans can be detected electrochemically as a biomarker for leptospiral infection diagnosis
PMID: 37599631
4
Elevated ETFB transcript levels are associated with poor overall survival in acute myeloid leukemia patients and represent a therapeutic target
PMID: 39533394
5
ETFB is among mitochondrial proteins decreased in cerebrospinal fluid and cortex of Alzheimer's disease patients, indicating mitochondrial dysfunction
PMID: 32711556
6
Multiple acyl-CoA dehydrogenase deficiency caused by ETFB mutations responds to riboflavin supplementation therapy
PMID: 33886098
Disease Associationsⓘ21
multiple acyl-CoA dehydrogenase deficiencyOpen Targets
0.83Strong
Elevated circulating glutaric acid concentrationOpen Targets
0.69Moderate
glutaric aciduriaOpen Targets
0.66Moderate
multiple acyl-CoA dehydrogenase deficiency, mild typeOpen Targets
0.37Weak
multiple acyl-CoA dehydrogenase deficiency, severe neonatal typeOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
chronic kidney diseaseOpen Targets
0.12Weak
Behcet's syndromeOpen Targets
0.07Suggestive
retinitis pigmentosaOpen Targets
0.07Suggestive
acute myeloid leukemiaOpen Targets
0.07Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.06Suggestive
X-linked retinal dysplasiaOpen Targets
0.06Suggestive
age-related macular degenerationOpen Targets
0.05Suggestive
Cone rod dystrophyOpen Targets
0.05Suggestive
Leber hereditary optic neuropathyOpen Targets
0.04Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.04Suggestive
Stargardt diseaseOpen Targets
0.04Suggestive
Leber congenital amaurosis 13Open Targets
0.04Suggestive
coloboma of optic nerveOpen Targets
0.04Suggestive
macular dystrophy with or without cone dysfunctionOpen Targets
0.04Suggestive
Glutaric aciduria 2BUniProt
Pathogenic Variants39
NM_001985.3(ETFB):c.253C>T (p.Arg85Ter)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2025→ Residue 85
NM_001985.3(ETFB):c.491G>A (p.Arg164Gln)Pathogenic
Glutaric acidemia IIb|Multiple acyl-CoA dehydrogenase deficiency|not provided
★★☆☆2025→ Residue 164
NM_001985.3(ETFB):c.61C>T (p.Arg21Ter)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2025→ Residue 21
NM_001985.3(ETFB):c.375+1G>ALikely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2025
NM_001985.3(ETFB):c.124T>C (p.Cys42Arg)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2024→ Residue 42
NM_001985.3(ETFB):c.61del (p.Arg21fs)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2024→ Residue 21
NM_001985.3(ETFB):c.178G>T (p.Glu60Ter)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2023→ Residue 60
NM_001985.3(ETFB):c.406C>T (p.Gln136Ter)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2023→ Residue 136
NM_001985.3(ETFB):c.375+1G>TLikely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★★☆☆2022
NM_001985.3(ETFB):c.491G>T (p.Arg164Leu)Likely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2026→ Residue 164
NM_001985.3(ETFB):c.368del (p.Gly123fs)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2026→ Residue 123
NM_001985.3(ETFB):c.632del (p.Pro211fs)Likely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024→ Residue 211
NM_001985.3(ETFB):c.694C>T (p.Gln232Ter)Likely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024→ Residue 232
NM_001985.3(ETFB):c.375G>C (p.Gln125His)Likely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024→ Residue 125
NM_001985.3(ETFB):c.216+2T>CLikely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024
NM_001985.3(ETFB):c.341_342delinsT (p.Lys114fs)Likely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024→ Residue 114
NM_001985.3(ETFB):c.426_427insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNTCTCCTGACCTCTAGATCCACCCGCCTCGGCCTCCCCAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGACAGCTGGATTTCTT (p.Asp143delinsPhePhePhePhePhePheXaaXaaXaaXaaSerProAspLeuTer)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024→ Residue 143
NM_001985.3(ETFB):c.81del (p.Gly28fs)Pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024→ Residue 28
NM_001985.3(ETFB):c.376-2A>CLikely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024
NM_001985.3(ETFB):c.214C>T (p.Gln72Ter)Likely pathogenic
Multiple acyl-CoA dehydrogenase deficiency
★☆☆☆2024→ Residue 72
View on ClinVar ↗
Related Genes
ACAA2Protein interaction98%HADHAProtein interaction97%ACOX1Protein interaction97%ACOX3Protein interaction96%ACAD8Protein interaction94%GCDHProtein interaction93%
Tissue Expression6 tissues
Liver
100%
Heart
34%
Brain
25%
Lung
12%
Ovary
12%
Bone Marrow
9%
Gene Interaction Network
Click a node to explore
ETFBACAA2HADHAACOX1ACOX3ACAD8GCDH
PROTEIN STRUCTURE
Preparing viewer…
PDB1EFV · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.74 [0.51–1.10]
RankingsWhere ETFB stands among ~20K protein-coding genes
  • #4,038of 20,598
    Most Researched117 · top quartile
  • #1,562of 5,498
    Most Pathogenic Variants39
  • #11,222of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedETFB
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis · 2022
1.00
2
Assignment of the human lens fiber cell MP19 gene (LIM2) to chromosome 19q13.4, and adjacent to ETFB.
PMID: 8197479
Somat Cell Mol Genet · 1994
0.90
3
Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer's disease.
PMID: 32711556
Mol Neurodegener · 2020
0.80
4
ATP5B and ETFB metabolic markers in children with congenital hydronephrosis.
PMID: 27840937
Mol Med Rep · 2016
0.70
5
Assignment of Etfdh, Etfb, and Etfa to chromosomes 3, 7, and 13: the mouse homologs of genes responsible for glutaric acidemia type II in human.
PMID: 8617498
Genomics · 1996
0.60