ETFB

electron transfer flavoprotein subunit beta

Basic information

Region (hg38): 19:51345169-51366388

Links

ENSG00000105379 ∙ NCBI:2109 ∙ OMIM:130410 ∙ HGNC:3482 ∙ Uniprot:P38117 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple acyl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR
• multiple acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• multiple acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• multiple acyl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple acyl-CoA dehydrogenase deficiency (Glutaric aciduria IIB)	AR	Biochemical	Dietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficial	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal	7145508; 8771170; 7912128; 12706375; 12815589; 18289905; 22231380

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ETFB gene.

• Multiple acyl-CoA dehydrogenase deficiency (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ETFB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				93	3	96
missense	1	5	74	6	2	88
nonsense	1	5				6
start loss			1			1
frameshift	3	8	2		1	14
inframe indel			3	1	1	5
splice donor/acceptor (+/-2bp)		7				7
splice region			7	12		19
non coding				46	31	77
Total	5	25	80	146	38

Variants in ETFB

This is a list of pathogenic ClinVar variants found in the ETFB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-51345217-C-A		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Mar 08, 2022)
19-51345218-C-T		Multiple acyl-CoA dehydrogenase deficiency	Uncertain significance (Aug 06, 2022)
19-51345219-G-A		Multiple acyl-CoA dehydrogenase deficiency	Uncertain significance (Aug 22, 2022)
19-51345219-G-T		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Jan 11, 2024)
19-51345232-C-T		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Dec 29, 2022)
19-51345243-C-T		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
19-51345247-G-A		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Sep 29, 2023)
19-51345251-T-G			Uncertain significance (Oct 01, 2012)
19-51345253-A-G		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Aug 15, 2022)
19-51345264-C-T		Multiple acyl-CoA dehydrogenase deficiency	Uncertain significance (Feb 08, 2022)
19-51345270-C-T		Multiple acyl-CoA dehydrogenase deficiency • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 30, 2024)
19-51345271-G-A		Multiple acyl-CoA dehydrogenase deficiency • not specified	Likely benign (Apr 08, 2024)
19-51345273-C-G		Multiple acyl-CoA dehydrogenase deficiency	Uncertain significance (Dec 09, 2023)
19-51345273-C-T		Multiple acyl-CoA dehydrogenase deficiency • Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
19-51345274-G-A		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Jan 18, 2024)
19-51345274-G-T		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Dec 14, 2023)
19-51345277-C-T		not specified • Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Jan 29, 2024)
19-51345278-G-A		Inborn genetic diseases	Uncertain significance (Apr 26, 2024)
19-51345282-G-A		Multiple acyl-CoA dehydrogenase deficiency	Uncertain significance (Sep 01, 2022)
19-51345289-C-T		Multiple acyl-CoA dehydrogenase deficiency	Likely benign (Jul 16, 2023)
19-51345292-G-T		Multiple acyl-CoA dehydrogenase deficiency	Uncertain significance (May 21, 2022)
19-51345303-T-A		Multiple acyl-CoA dehydrogenase deficiency	Uncertain significance (Jul 06, 2022)
19-51345306-TCA-T		Multiple acyl-CoA dehydrogenase deficiency	Likely pathogenic (Jul 25, 2023)
19-51345309-C-T		Inborn genetic diseases	Uncertain significance (Oct 20, 2024)
19-51345310-A-G		Multiple acyl-CoA dehydrogenase deficiency • ETFB-related disorder	Likely benign (Mar 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ETFB	protein_coding	protein_coding	ENST00000354232	5	21250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0166	0.962	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.423	183	200	0.916	0.0000123	2185
Missense in Polyphen		73	80.486	0.90699		807
Synonymous	0.111	88	89.3	0.985	0.00000577	776
Loss of Function	2.01	5	12.7	0.393	6.92e-7	140

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000584	0.0000584
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:25416781, PubMed:15159392, PubMed:15975918). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (Probable). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:7912128). ETFB binds an AMP molecule that probably has a purely structural role (PubMed:8962055, PubMed:15159392, PubMed:15975918). {ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:25416781, ECO:0000269|PubMed:7912128, ECO:0000269|PubMed:8962055, ECO:0000303|PubMed:17941859, ECO:0000305}.
• Disease: DISEASE: Glutaric aciduria 2B (GA2B) [MIM:231680]: An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. {ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:7912128}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Protein methylation;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.278

Intolerance Scores

• loftool: 0.122
• rvis_EVS: 0.64
• rvis_percentile_EVS: 83.98

Haploinsufficiency Scores

• pHI: 0.381
• hipred: N
• hipred_score: 0.210
• ghis: 0.397

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Etfb

Gene ontology

• Biological process: electron transport chain;fatty acid beta-oxidation using acyl-CoA dehydrogenase
• Cellular component: mitochondrion;mitochondrial matrix;cytosol
• Molecular function: protein binding;electron transfer activity