ETFA

electron transfer flavoprotein subunit alpha

Basic information

Region (hg38): 15:76188554-76311730

Links

ENSG00000140374 ∙ NCBI:2108 ∙ OMIM:608053 ∙ HGNC:3481 ∙ Uniprot:P13804 ∙ 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 IIA)	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; 1882842; 1430199; 12815589; 18289905; 20736750; 22231380

ClinVar

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

• Multiple acyl-CoA dehydrogenase deficiency (373 variants)
• not provided (80 variants)
• not specified (23 variants)
• Inborn genetic diseases (23 variants)
• Glutaric acidemia type 2A (16 variants)
• Glutaric acidemia IIa (5 variants)
• ETFA-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ETFA 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				95		95
missense	1	3	87	3		94
nonsense	4	3				7
start loss			1			1
frameshift	10	14				24
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		16				16
splice region			6	41		47
non coding			23	89	34	146
Total	15	37	112	187	34

Highest pathogenic variant AF is 0.0000789

Variants in ETFA

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

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

Position	Type	Phenotype	Significance	ClinVar
15-76192043-C-G		not specified	Uncertain significance (Jan 03, 2022)
15-76192047-C-A		not specified	Uncertain significance (Mar 20, 2023)
15-76192049-C-G		not specified	Uncertain significance (Mar 20, 2023)
15-76203746-G-A		not specified	Uncertain significance (Jan 19, 2024)
15-76203771-T-C		not specified	Uncertain significance (Oct 06, 2023)
15-76203780-C-T		not specified	Uncertain significance (Apr 13, 2022)
15-76203785-G-A		not specified	Uncertain significance (Oct 20, 2023)
15-76203788-A-G		not specified	Uncertain significance (Mar 22, 2023)
15-76203792-A-C		not specified	Uncertain significance (Feb 05, 2024)
15-76203806-A-C		not specified	Uncertain significance (Aug 01, 2022)
15-76203839-C-A		not specified	Uncertain significance (Jan 23, 2024)
15-76203950-T-C		not specified	Uncertain significance (Sep 29, 2022)
15-76203962-C-T		not specified	Uncertain significance (Feb 15, 2023)
15-76204002-C-T		not specified	Uncertain significance (Nov 03, 2023)
15-76204014-A-C		not specified	Uncertain significance (Nov 30, 2022)
15-76204029-A-C		not specified	Uncertain significance (Dec 19, 2023)
15-76204066-G-T		not specified	Uncertain significance (Jul 25, 2023)
15-76204074-G-A		not specified	Uncertain significance (Jun 28, 2022)
15-76204106-C-A		not specified	Uncertain significance (Aug 22, 2023)
15-76204106-C-G		not specified	Uncertain significance (Jan 16, 2024)
15-76204109-G-A		not specified	Uncertain significance (Jan 03, 2024)
15-76204112-C-T		not specified	Uncertain significance (May 25, 2022)
15-76204113-G-A		not specified	Likely benign (Mar 29, 2022)
15-76204216-G-T		not specified	Uncertain significance (Jul 14, 2021)
15-76204230-T-G		not specified	Uncertain significance (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ETFA	protein_coding	protein_coding	ENST00000557943	12	96118

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00292	0.995	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	139	179	0.776	0.00000865	2118
Missense in Polyphen		62	78.882	0.78599		917
Synonymous	0.891	53	61.9	0.856	0.00000291	678
Loss of Function	2.66	8	21.2	0.377	0.00000113	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000366	0.000365
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000309	0.000308
Middle Eastern	0.000163	0.000163
South Asian	0.000458	0.000457
Other	0.000164	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:27499296, PubMed:15159392, PubMed:15975918, PubMed:9334218, PubMed:10356313). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:9334218). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:1882842, PubMed:1430199). {ECO:0000269|PubMed:10356313, ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:1430199, ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:27499296, ECO:0000269|PubMed:9334218, ECO:0000303|PubMed:17941859, ECO:0000305|PubMed:1882842}.
• Disease: DISEASE: Glutaric aciduria 2A (GA2A) [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:1430199, ECO:0000269|PubMed:1882842, ECO:0000269|PubMed:9334218}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.730

Intolerance Scores

• loftool: 0.245
• rvis_EVS: 0.08
• rvis_percentile_EVS: 60.09

Haploinsufficiency Scores

• pHI: 0.176
• hipred: Y
• hipred_score: 0.694
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.924

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Etfa

Zebrafish Information Network

• Gene name: etfa
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: swollen

Gene ontology

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