ETFDH

Chr 4AR

electron transfer flavoprotein dehydrogenase

Also known as: ETFQO, MADD

NCBI Gene: 2110 ENSG00000171503 UniProt: Q16134 OMIM: 231675

The protein accepts electrons from electron transfer flavoprotein (ETF) and reduces ubiquinone in the mitochondrial respiratory chain. Mutations cause glutaric acidemia IIC, an autosomal recessive disorder of fatty acid oxidation. Loss of function mutations disrupt the electron transport chain, leading to impaired fatty acid beta-oxidation and accumulation of organic acids.

GeneReviews OMIM ResearchSummary from OMIM, UniProt

This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. Mutations in this gene are associated with glutaric acidemia. Alternatively spliced transcript variants that encode distinct isoforms have been observed. [provided by RefSeq, Aug 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.041 OMIM phenotype

Clinical Summary— ETFDH

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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 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

160 unique Pathogenic / Likely Pathogenic· 170 VUS of 589 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ETFDH

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.36

OE 0.74 (0.54–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.39Z-score

OE missense 0.94 (0.86–1.03)

314 obs / 334.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.54–1.04)

0≤0.351.4

Missense OE?0.94 (0.86–1.03)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 24 / 32.3Missense obs/exp: 314 / 334.2Syn Z: -0.16

ClinVar Variant Classifications

589 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50

Likely Pathogenic110

VUS170

Likely Benign228

Benign7

Conflicting15

Pathogenic

110

Likely Pathogenic

170

VUS

228

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	39	5	6	0	50
Likely Pathogenic	76	31	3	0	110
VUS	0	153	12	5	170
Likely Benign	0	1	109	118	228
Benign	0	0	7	0	7
Conflicting	—				15
Total	115	190	137	123	580

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap ETFDH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →