GeneBe

ETFDH

electron transfer flavoprotein dehydrogenase

Basic information

Region (hg38): 4:158671968-158710742

Links

ENSG00000171503 ∙ NCBI:2110 ∙ OMIM:231675 ∙ HGNC:3483 ∙ Uniprot:Q16134 ∙ 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 (Definitive), 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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Multiple acyl-CoA dehydrogenase deficiency (Glutaric aciduria IIC)ARBiochemicalDietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficialBiochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal7145508; 8771170; 12815589; 16527485; 17412732; 17584774; 18289905; 19208393; 19249206; 19758981; 19783111; 20138856; 20370797; 20837308; 21088898; 21616504; 21907580; 22041377; 22231380; 22664151; 23106979; 23893693

ClinVar

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

  • Multiple_acyl-CoA_dehydrogenase_deficiency (880 variants)
  • not_provided (148 variants)
  • Glutaric_acidemia_type_2C (87 variants)
  • not_specified (59 variants)
  • Inborn_genetic_diseases (58 variants)
  • ETFDH-related_disorder (29 variants)
  • Glutaric_acidemia_IIc (9 variants)
  • Glutaric_acidemia_iic,_late-onset (4 variants)
  • See_cases (2 variants)
  • Abnormality_of_metabolism/homeostasis (2 variants)
  • Myopathy (2 variants)
  • Hypertrophic_cardiomyopathy (1 variants)
  • Distal_spinal_muscular_atrophy (1 variants)
  • Acyl-CoA_dehydrogenase_deficiency,_glutaric_acidemia_type_II (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ETFDH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004453.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
9
clinvar
234
clinvar
 243
missense
20
clinvar
112
clinvar
242
clinvar
12
clinvar
 386
nonsense
31
clinvar
19
clinvar
 50
start loss
3
1
 4
frameshift
44
clinvar
46
clinvar
1
clinvar
 91
splice donor/acceptor (+/-2bp)
6
clinvar
39
clinvar
1
clinvar
2
clinvar
 48
Total 104 216 254 248 0

Highest pathogenic variant AF is 0.000203004

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ETFDHprotein_codingprotein_codingENST00000511912 1337499
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
2.78e-130.42812561001371257470.000545
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.3933143340.9400.00001664022
Missense in Polyphen139148.760.934361713
Synonymous-0.1631191171.020.000006091196
Loss of Function1.362432.30.7420.00000152397

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001820.00181
Ashkenazi Jewish0.0006040.000496
East Asian0.0001650.000163
Finnish0.00009620.0000924
European (Non-Finnish)0.0006110.000607
Middle Eastern0.0001650.000163
South Asian0.0001990.000196
Other0.0005090.000489

dbNSFP

Source: dbNSFP

Function
FUNCTION: Accepts electrons from ETF and reduces ubiquinone.;
Disease
DISEASE: Glutaric aciduria 2C (GA2C) [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:12359134, ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:16527485, ECO:0000269|PubMed:17412732, ECO:0000269|PubMed:19249206, ECO:0000269|PubMed:20370797}. 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
0.315

Intolerance Scores

loftool
0.286
rvis_EVS
-0.56
rvis_percentile_EVS
19.54

Haploinsufficiency Scores

pHI
0.0543
hipred
N
hipred_score
0.333
ghis
0.550

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.951

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Etfdh
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name
etfdh
Affected structure
glial cell
Phenotype tag
abnormal
Phenotype quality
malformed

Gene ontology

Biological process
response to oxidative stress;electron transport chain;respiratory electron transport chain;fatty acid beta-oxidation using acyl-CoA dehydrogenase
Cellular component
mitochondrial matrix;integral component of mitochondrial inner membrane;mitochondrial membrane
Molecular function
electron-transferring-flavoprotein dehydrogenase activity;electron transfer activity;oxidoreductase activity;oxidoreductase activity, oxidizing metal ions with flavin as acceptor;metal ion binding;quinone binding;ubiquinone binding;flavin adenine dinucleotide binding;4 iron, 4 sulfur cluster binding